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					Psychotherapy
                            STUDY DETAILS – adolescents; SSRI ± psychotherapy vs SSNRI ± psychotherapy
Reference [1] (Brent et al 2008) Brent, D., Emslie, G. et al (2008). 'Switching to another SSRI or to venlafaxine with or without cognitive
behavioral therapy for adolescents with SSRI-resistant depression - The TORDIA randomized controlled trial', Jama-Journal Of The American
Medical Association, 299 (8), 901-913.
Affiliation/source of funds [2] Funding from National Institute of Mental Health, Bethesda, Maryland, United States
Brown University, University of Texas Southwestern Medical Center at Dallas, University of Texas Medical Branch, Galveston, University of
Pittsburgh, Kaiser Permanente-Portland. Financial disclosures: Pfizer, Philip Morris, Bristol-Myers Squibb, Roche, Solvay Pharmaceuticals Inc,
Abcomm Inc, Eli Lilly, Organon, Shire, Somerset, Forest Laboratories, Janssen, JDS, Novartis, Wyett, Abbott Laboratories, CENEREX,
Cephalon, Cypress Bioscience, Cyberonics, Johnson & Johnson, McNeil, AstraZeneca, Jazz Pharmaceuticals, Ortho-McNeil, Otsuka, Wyeth
Ayerst
Study design [3]                         Level of evidence [4]                     Location/setting [5]
RCT                                      Interventional level II                   6 academic & community clinics in United States
Intervention 1 [6]                       Intervention 2 [6]                        Intervention 3 [6]             Intervention 4 [6]
Different a SSRI (paroxetine,            Different a SSRI (paroxetine,             Venlafaxine (150-225 mg)       Venlafaxine (150-225 mg)
Citalopram or fluoxetine 20-40 mg)       Citalopram or fluoxetine 20-40 mg)        Sample size [7]                plus CBT (median 9
Sample size [7]                          plus CBT (median 9 sessions)              83                             sessions)
85                                       Sample size [7]                                                          Sample size [7]
                                         83                                                                       83
Selection criteria
Inclusion criteria –
Adolescents aged 12-18 in active treatment for MDD (DSM IV) with SSRI resistance (CDRS-R total score ≥40 & CGI-S ≥4 despite being
treated with an SSRI for ≥8 weeks, the last 4 of which was at a dosage of ≥40mg/day of fluoxetine or its equivalent) or participants who, after
attempting dosage comparable to 40 mg fluoxetine, could only tolerate dose equivalent of 20 mg fluoxetine for ≥4 weeks (19/33 4
participants;5.7%). Only participants in whom the CDRS-R decreased <30% & still had significant depressive symptoms at re-assessment 2
weeks after evaluation (while remaining on initial SSRI) were included.
Exclusion criteria –
Participants with: ≥2 adequate trials of an SSRI; history of non-response to venlafaxine (≥4 weeks at dosage of ≥150 mg), or to CBT(≥7
sessions); currently receiving CBT; taking psychoactive medications, except those prescribed stable doses (≥12 weeks) of stimulants,
hypnotics (trazodone, zolpidem, zaleplon), or antianxiety agents (clonazepam, lorazepam); diagnoses of bipolar spectrum disorder, psychosis,
pervasive developmental disorder or autism, eating disorders, substance abuse or dependence, or hypertension; pregnant or breastfeeding
females; females having unprotected sex.
Patient characteristics [10]
Median SSRI treatment duration prior to study entry 17 weeks (IQR 16.5 weeks). Patients had a median of 8 sessions of psychotherapy in the
previous 12 weeks (IQR 5 sessions). Median household income $61 000.
SSRI ± CBT group – Mean age = 16.0±1.6 years, 82.1% White, 72.0% female, 50.6% college graduates
Venlaxafine ± CBT – Mean age = 15.8±1.5 years, 83.7% White, 67.5% female, 45.0% college graduates
Length of follow-up [11] Length of           Outcome(s) measured [12] Primary – global functioning on the CGAS, CGI-S
treatment: 12 weeks                          Secondary – depressive symptoms on the CDRS-R, suicidal ideation
                                                              INTERNAL VALIDITY
Allocation [13]                              Comparison of study       Blinding [15]                     Treatment/                  Follow-up
Randomization balanced within & across       groups [14]               Study participants, clinicians,   measurement bias            (ITT) [17]
sites with respect to incoming treatment     Similar at baseline on    & independent evaluators          [16]                        ITT
medication, comorbid anxiety, chronic        demographics and          blinded to medication             44.2% accuracy in
depression (duration ≥24 months), &          baseline outcome          treatment assignment.             pharmacotherapist
suicidal ideation (BDI item 9 ≥2), using     variables, except         Independent evaluators            guessing treatment
variation of Efron’s biased coin toss.       venlaxafine group had     blinded to CBT assignment,        allocation (χ2=4.57;
Participants initially treated with          lower levels of           however in 64 cases, blinding     p=.03). 58.3% accuracy
citalopram, sertraline, or fluvoxamine       depressive symptoms       was compromised, due to           in independent
were randomized to fluoxetine or             on BDI (p=0.03) and       participant disclosure of         evaluators
paroxetine. Participants initially treated   PTSD (p=0.04)             receiving CBT.                    Guessing CBT
with fluoxetine, were switched to                                                                        assignment (χ2=5.14;
paroxetine & vice versa.                                                                                 p=.02).
Overall quality assessment (descriptive) [18] Average quality. Four treatment conditions were not compared against each other, only when
combined in different ways.
                                                                   RESULTS



Depression in adolescents and young adults                                                                                      769
Outcome [19]                Intervention group [20]      Control group [21] SNRI   Measure of effect/effect size [22]
                            SSRI ± CBT                   ± CBT
Global functioning on       Pre: 50.3±7.8                Pre: 50.9±7.6
CGAS (1 – 100)              6 weeks: 58.9±11.5           6 weeks: 59.7±9.7
                            12 weeks: 63.3±11.9          12 weeks: 64.8±11.1
Global functioning on the   Pre: 4.5±0.6                 Pre: 4.4±0.7              No difference between medication groups
CGI-Severity (1-7)          6 weeks: 3.5±1.0             6 weeks: 3.4±1.1
                            12 weeks:2.9±1.2             12 weeks: 2.8±1.2
Depressive symptoms on      Pre: 59.8±10.6               Pre: 57.8±10.1
the CDRS-R (17-113)         6 weeks: 42.3±14.0           6 weeks: 42.6±13.2
                            12 weeks: 37.9±13.7          12 weeks: 37.0±13.1
Depressive symptoms on      Pre: 21.9±10.6               Pre: 57.8±10.1
the BDI                     6 weeks: 42.3±14.0           6 weeks: 42.6±13.2
                            12 weeks:37.9±13.7           12 weeks: 37.0±13.1
Suicidal Ideation           Pre: 42.8±22.0               Pre: 40.4±22.6
Questionnaire – Jr          6 weeks: 33.3±20.7           6 weeks: 35.1±21.5
                            12 weeks: 31.6±17.9          12 weeks:31.5±19.7
                            Clinical importance (1-4) [26]                         Relevance (1-5) [27]

Any other adverse effects [28]

                                                             EXTERNAL VALIDITY

Generalisability [29]

Applicability [30]

Comments [31]




770                                                                Depression in adolescents and young adult
                                                                 STUDY DETAILS
Reference [1] (Brent et al 1998) Brent, D. A., Kolko, D. J. et al (1998). 'Predictors of treatment efficacy in a clinical trial of three psychosocial
treatments for adolescent depression', J Am Acad Child Adolesc Psychiatry, 37 (9), 906-914.
(Brent et al 1997) Brent, D. A., Holder, D. et al (1997). 'A clinical psychotherapy trial for adolescent depression comparing Cognitive, Family and
Supportive Therapy', Arch Gen Psychiatry, 54 (9), 877-885.(see also Kolko et al 2000)
(Birmaher et al 2000) Birmaher, B., Brent, D. A. et al (2000). 'Clinical outcome after short-term psychotherapy for adolescents with major
depressive disorder', Arch Gen Psychiatry, 57 (1), 29-36.
Affiliation/source of funds [2] Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, supported by a
National Institute of Mental Health (NIMH) Grant
Study design [3] RCT                  Level of evidence [4] Interventional level II                Location/setting [5] Pittsburgh, United States
Intervention [6] CBT 12-16 sessions over 12-16 weeks delivered by          Comparator(s) [8]
an experienced therapist. One hour group and one hour individual           SBFT (n=35), (combined with a problem solving model)
session per week.                                                          Or NST (n=35) (consisting of support, affect clarification and active
Sample size [7] 107 over 3 groups, CBT (n=37), all groups were             listening
similar on almost all treatment variables related to treatment             Both 12-16 sessions over 12-16 weeks delivered by an experienced
intensity and duration and the number, characteristics and                 therapist, one hour group and one hour individual session per week.
experience of therapists
Birmaher (2000) – After initial trial, 62 participants received 2-4
booster sessions in the same treatment group as for the trial
Selection criteria; Inclusion criteria – Adolescent outpatients with DSM-III-R Major depression aged between 13 and 18 years, living with at
least one parent or guardian, BDI of ≥13, clinical referral, response to advertisement to volunteer to participate
Exclusion criteria – psychosis; bipolar I or II disorder; obsessive-compulsive disorder; eating disorder; substance abuse within past 6 months;
ongoing physical or sexual abuse; pregnancy or chronic medical illness;
Patient characteristics [10] Intervention group – adolescents 13-18 years of age with normal intelligence living with at least one parent or
guardian and with SDM-III-R major depressive disorder and an intake BDI of ≥13, 75.7% female, 75.7% white, mean age 15.7 years, comorbid
diagnoses 16.2% dysthymic, 37.8% anxiety disorder and 16.2% disruptive disorder,
Comparator group(s) – same as for intervention group, SBFT group (77.1% female, 88.6% white, mean age 15.4 years, comorbid diagnoses
25.7% dysthymic, 28.6% anxiety disorder and 22.9% disruptive disorder), NST group (74.3% female, 85.7% white, mean age 15.7 years,
comorbid diagnoses 25.7% dysthymic, 28.6% anxiety disorder and 22.9% disruptive disorder)
Length of follow-up [11] 6 weeks after end of                 Outcome(s) measured [12] Primary – functioning using CGAS, FAD,
treatment,                                                    Secondary – symptoms of depression using BDI, K-SADS,
(Birmaher et al 2000) follow-up to 2 years
                                                                INTERNAL VALIDITY

Allocation [13]         Comparison of study        Blinding [15]           Treatment/                 Follow-up (ITT) [17]
Randomisation           groups [14] no             interviewers blind      measurement bias           94 (87.8%) received a 6 week interview and
using the Begg and      significant baseline       to treatment            [16]                       BDI; at 12 weeks 99 (92.5%) received a final
Iglewicz                demographic or             status                  Groups likely treated      interview and 97 (90.7%) had a final BDI
modification of the     clinical differences                               and measured the           77.6% (n=83) completed all 8 interviews, 14%
Efron biased coin       among the groups                                   same except for            9n=15) completed all but one, 5.6% (n=6)
toss.                                                                      intervention               completed 4-6 interviews, and 2.8% (n=3)
                                                                                                      completed 2 or less interviews
Overall quality assessment (descriptive) [18] Individually average – however, with the inclusion of the second and third studies in which the
details of randomisation and 2 year follow-up have been added, the combination of both articles makes it a good quality study
                                                                        RESULTS

Outcome [19]                 Intervention group [20]                 Control group [21]                            Measure of effect/effect size
                                               CBT                               SBFT       NST                    [22]
MDD episode                  Intake          100% (n=37)             Intake    100% (n=35) 100% (n=35)             CBT showed lower rate of MDD
                             6 weeks          60% (n=35)             6 weeks 65.5% (n=29) 63.3% (n=30)             at end of treatment compared
                                                                     12-16 wks 32.3% (n=31) 42.4% (n=33)           with NST (17.1% vs 42.4%,
                             12-16 weeks      17.1% (n=35)                                                         p=.02),
Remission of depressive                         CBT                              SBFT                NST           CBT - higher rate of remission
symptoms                     Intake              0                   Intake        0                 0             (64.7%) than SBFT (37.9%,
                             6 weeks            16.7%                6 weeks     6.2%               16.7%          p=.03) or NST (39.4%, p=.04)
                                                                                                                   and more rapid relief of
                             12-16 weeks        60%                  12-16 weeks 29%                36.4%          depression (vs SBFT, p=.02, vs
                                                                                                                   both treatments p=.03)




     Depression in adolescents and young adults                                                                                          771
Depressive symptoms                             CBT                             SBFT          NST                 Failure to achieve clinical
using BDI mean + SD          Intake             24.3±8.1             Intake    22.6±8.2 25.7±7.8                  remission was 4.0 times more
                             6 weeks            10.7±11.1            6 weeks 13.7±9.3 13.4±10.7                   likely to occur in SBFT as in CBT
                                                                                                                  (95% CI = 1.2, 12.6) and 3.1
                             12-16 weeks        5.7±8.6              12-16 weeks 9.1±9.1 9.8±11.4                 times more likely in NST than
                                                                                                                  CBT (95% CI – 1.1,9.1) [25]
                             Overall results - not related to        Overall results - not related to treatment   As the number of adverse
                             treatment groups                        groups                                       predictors increased, NST less
Predictors of recovery       No Recovery (n=18)                      Recovery (n=86)                              affective (x2=6.26,df =1, p=0.01
and recurrence –             Baseline K-SADS 3.1±0.5                 Baseline K-SADS         2.8±0.5              Pts who had NST were 5.8 times
Depressive symptoms          posttreatment K-SADS 2.4(±0.7           posttreatment K-SADS 1.5±0.5                 more likely than those who
using K-SADS and BDI                                                                                              received CBT to have MDD at
mean and SD                                                                                                       the posttreatment (95% CI = 1.5,
                             Baseline BDI      29.0 ±9.4             Baseline BDI      23.1±7.5
                                                                                                                  23.5)
                             posttreatment BDI 17.8 ±13.7            posttreatment BDI 5.9 ±7.1
Predictors of recovery or    No Recovery (n=18)                      Recovery (n=86)
recurrence - General         posttreatment     56.3±10.1             posttreatment         65.8±8.5
functioning using CGAS
mean and SD
Predictors of recovery or    No Recovery (n=18)                      Recovery (n=86)
recurrence - Functioning     posttreatment      2.8±0.5              posttreatment           2.5±0.5
using FAD-GF, mean
and SD
Demographic and              Persistent recovery (n=40)               Persistent Depression (n=22)                Intermediate Course (n=42)
clinical predictors of       At intake      K-SADS 2.7±0.5           At intake                                    At intake K-SADS 2.8±0.5
persistent recovery or       posttreatment K-SADS 1.4±0.4                  K-SADS 3.0±0.5                         posttreatment
persistent depression
during 2 year follow-up      posttreatment BDI 4.4±5.2               posttreatment                                          K-SADS 1.6±0.5
period, mean and SD          posttreatment CGAS 66.5±9.1                   K-SADS 2.3±0.8                         posttreatment
                             posttreatment FAD-GF 2.4±0.5            posttreatment                                          BDI     6.9±7.2
                                                                           BDI 17.8±14.2                          posttreatment
                                                                     posttreatment                                          CGAS 64.9±7.8
                                                                           CGAS 57.8±10.7                         posttreatment
                                                                     posttreatment                                          FAD-GF 2.5±0.5
                                                                           FAD-GF 2.8±0.4


                             Clinical importance (1-4) [26] CBT appeared to be more efficacious that other        Relevance (1-5) [27] more rapid
                             two treatments, however long term the differences were not significant               remission from depressive
                                                                                                                  symptoms
Any other adverse effects [28] nil stated
                                                                EXTERNAL VALIDITY
Generalisability [29] likely generalisable
Applicability [30] Benefits likely to outweigh harms, CBT showed greater effect in quicker time than the other treatments therefore significant
benefit re cost and risk of suicide, however not significant difference long term
Comments [31] highlights the differences in recruitment strategies and how they impact on outcomes, the authors identified recruitment source
as a predictor of outcome and comment that the results may explain why treatments developed in research clinics fail to generalize to the
community e.g. suicide patients went to emergency departments and were not seen at clinics, also the patient/therapist ratio and treatment
hours were more generous than most patients can afford or would be allowed by their health fund, also many diagnoses excluded, exclusion
criteria was quite extensive
     BDI=Beck Depression Inventory (range 0-39 with higher scores indicating greater number of symptoms of depression); CBT=Cognitive Behavioural
     Therapy; CGAS=Children’s Global Assessment Scale: FAD-GF=Family Assessment Device-General Functioning: K-SADS-PE=The School Age Schedule
     for Affective Disorders and Schizophrenia, Present and Lifetime Versions; MDD= Major Depressive Disorder; NST=Nondirective Supportive Therapy;
     SBFT=Systemic-Behavioural Family Therapy;




     772                                                                    Depression in adolescents and young adult
                                                                     STUDY DETAILS
Reference [1] (Byford et al 2007) Byford, S., Barrett, B. et al (2007). 'Cost-effectiveness of selective serotonin reuptake inhibitors and routine
specialist care with and without cognitive-behavioural therapy in adolescents with major depression', British Journal of Psychiatry 191, 521-527.
(refer to (Goodyer et al 2007))
Affiliation/source of funds [2] Centre for the Economics of Mental Health, Institute of Psychiatry, King’s College, London; Division of
Epidemiology and Health Sciences, University of Manchester; Developmental Psychiatry Section, Department of Psychiatry, University of
Cambridge; Department of Child and Adolescent Psychiatry, Royal Manchester Children’s Hospital, Manchester; Cambridge Specialist Child
and Adolescent Mental Health Service, Brookside Clinic, Cambridge;
Study design [3]                       Level of evidence [4]              Location/setting [5] Mental Health Clinics in Manchester and Cambridge
Psuedo RCT                             Interventional level III-1         UK
Intervention [6] SSRIs (fluoxetine) and clinical care with CBT for 12       Comparator(s) [8] SSRIs only with option of 9 outpatient sessions over
weeks, followed by 6 maintenance sessions every 2 weeks and final           28 weeks
session at 28 weeks                                                         Sample size [9] (n=103) full data for (n=92)
Sample size [7] (n=105) full data for (n=96)
Selection criteria
Inclusion criteria – Adolescents 11-17 years, with DSM-IV criteria for major depressive disorder,
Exclusion criteria – Adolescents with depression that remit rapidly as identified on a brief psychological intervention taken pre-randomisation
Patient characteristics [10]
Intervention group – n=96, 73% female (n=70), Median age 14 (range 11-17), study centre Manchester 70% (n=67), Cambridge 30% (n=29),
Comparator group – n=92, 72% female (n=66), median age 14 (range 11-17), study centre Manchester 68% (n=63), Cambridge 32% (n=29),
Length of follow-up [11] varied between 21-51            Outcome(s) measured [12] Primary – total cost per young person over 28 weeks, Cost
weeks mean 29 weeks in both groups                       effectiveness using ICER’s,
                                                                    INTERNAL VALIDITY
Allocation [13]       Comparison of study groups              Blinding [15]              Treatment/                    Follow-up (ITT) [17]
Randomisation         [14]                                    Assessors masked to        measurement bias [16]         Full economic data
using a remote        Stochastic minimisation was used        treatment allocations      Unlikely as patients          available for 90% of
independent           to ensure balance on severity,          carried out assessments    measured and treated the      participants 96 SSRIs +
statistical centre.   centre, gender, comorbid                at baseline, 6, 12, and    same except for               CBT and 92 SSRIs only
                      behaviour disorder and age. No          28 weeks                   intervention
                      significant differences in baseline
                      characteristics between groups
Overall quality assessment (descriptive) [18] average quality study

                                                                        RESULTS

Outcome [19]                      Intervention group [20] n=96            Control group [21]                Measure of effect/effect size [22]
                                             Mean SD                      n=92                              Difference (95% CI)
                                  Baseline     55±21                                Mean SD                   -4 (-10, 2)
Health related quality of life    12 weeks 65±18                          Baseline    59±21                   -3 (-9, 3)
– patient rated                   28 weeks 72±19                          12 weeks 67±21                       0 (-6, 6)
EQ-5D VAS                                                                 28 weeks 72±22
Health related quality of life    Baseline     0.49±0.30                  Baseline 0.50±0.29                 -0.02 (-0.10, 0.6)
EQ-5D utilities                   12 weeks     0.68±0.30                  12 weeks 0.73±0.25                 -0.07 (-0.14, 0.01)
                                  28 weeks     0.74±0.30                  28 weeks 0.78±0.26                 -0.04 (-0.12, 0.04)
Cost effectiveness quality        28 weeks     0.36±0.15                  28 weeks 0.38±0.14                -0.02 (-0.07, 0.05 )
adjusted life years                                                                                         P 0.137
QALY’s
Mental health impairment          28 weeks 15.39±8.58                     28 weeks 14.52±8.26               1.24 (-1.05, 3.52)
HoNOSCA                                                                                                     P 0.287




Depression in adolescents and young adults                                                                                         773
Total cost over 28 week          N=96                                     N=92
period                                          Mean SD                              Mean SD                Mean difference (95% CI)
                                 Health services                          Health services
                                               3512±9452                              919±1150              2511 (568, 4453)
                                 Intervention sessions                    Intervention sessions
                                               752±683                                262±196               491 (344, 639)
                                 Hospital services                        Hospital services
                                              2652±9388                               551±1109              2017 (83, 3950)
                                 Community health services                Community health services
                                                68±96                                  74±126               -9 (-41, 22)
                                 Medication                               Medication
                                                40±50                                  32±47                 9 (-5, 23)
                                 Education                                Education
                                              3400±3556                            3575±4089                -55 (-1104, 994)
                                 Social services                          Social services
                                                16±70                                133±1154               -122 (-349, 125)
                                 Voluntary sector services                Voluntary sector services
                                                 6±33                                  14±69                -10 (-24, 4)
                                 Private sector services                  Private sector services
                                                 7±55                                  0±3)                 7 (-4, 19)
                                 Total costs                               Total costs
                                            6940±11 122                                4640±4516            2340 (-91, 4772) P 0.059
                                 Total costs per week                     Total costs per week
                                             244±403                                    161±155             85 (-3, 173) P 0.057
Sensitivity analysis of 28       N=96                                     N=92                              Mean differences (95% CI)
week cost per participant                  Mean SD                                Mean SD
                                 Main analysis                            Main analysis
                                           6940 ±11 122                          4640±4516                  2340 (-91, 4772) P 0.059
                                 Varying grade/profession of              Varying grade/profession of
                                 therapist                                therapist
                                           6614±11 074                            4531±4499                 2126 (-294, 4546) P 0.085
                                 Including full cost of missed            Including full cost of missed
                                 appointments                             appointments
                                           7131±11 089                            4736±4516                 2436 (10, 4862) P 0.049

                                 Including cost of supervisors’ time      Including cost of supervisors’
                                           7200±11 119                    time                               2444 (14, 4874) P 0.049
                                                                                  4799±4525
                                 Excluding high cost individuals          Excluding high cost individuals
                                            5531±5180                             4640±4516                 890 (-517, 2297) P 0.202


                                 Including travel costs and parent        Including travel costs and
                                 productivity losses                      parent productivity losses        2357 (-178, 4892) P 0.068
                                             7129±11 347                           4836±5171
                                 Applying national unit costs             Applying national unit costs
                                           6981±11 198                             4630±4502                2376 (-63, 4815) P 0.056
                                 Clinical importance (1-4) [26]                                             Relevance (1-5) [27]
                                 Clinical benefits of combined treatment do not appear to justify the       Cost effectiveness of combined
                                 cost                                                                       therapy not proven


Any other adverse effects [28] none stated
                                                                 EXTERNAL VALIDITY
Generalisability [29] unsure if applicable to the Australian population




774                                                                    Depression in adolescents and young adult
Applicability [30] no apparent cost effective benefit of combination therapy
Comments [31] this study concludes that a combination of SSRIs and CBT is not cost effective
CBT=Cognitive Behavioral Therapy; CGAS=Children’s Global Assessment Scale; EQ-5D=Economic evaluation/cost utility analysis; HoNOSCA=Health of
the Nation Outcome Scale for Children and Adolescents; ICER= Incremental cost-effectiveness ratios; K-SADS-PL=Kiddie Schedule for Affective Disorders
and Schizophrenia, Present and Lifetime Version; QALY’s=Quality Adjusted Life Years; SSRI =Selective Serotonin Reuptake Inhibitors; VAS= Visual
Analogue Scale;




Depression in adolescents and young adults                                                                                               775
                                                              STUDY DETAILS
Reference [1] (Clarke et al 1992) Clarke, G., Hops, H. et al (1992). 'Cognitive-Behavioral Group Treatment Of Adolescent Depression -
Prediction Of Outcome', Behavior Therapy, 23 (3), 341-354.
Affiliation/source of funds [2] Oregon Health Sciences University and Oregon Research Institute
Supported in part by a grant from the National Institute of Mental Health
Study design [3]                                        Level of evidence [4]        Location/setting [5]
Prospective inception cohort (for the purposes of       II prognostic                Not stated
prognosis)
Patient characteristics [10]                                                         Sample size [7]
Not stated                                                                           N= 37randomised to treatment (19 on waitlist excluded)
                                                                                     Length of follow-up [11]
                                                                                     Posttreatment (14 weeks from baseline)
Selection criteria
Inclusion criteria: adolescents meeting Research Diagnostic Criteria (RDC) diagnosed using the K-SADS
Exclusion criteria : not stated
Prognostic factor(s):                                         Data collection method
Demographics                                                  age and gender
Psychosocial variables                                        Frequency of Self-Reinforcement Attitudes Scale (Heiby, 1982)
                                                              Personal Beliefs Inventory (Munoz & Lewinsohn, 1976)
                                                              State Anxiety Scale (Spielberger, 1973)
                                                              Subjective Probability Questionnaire (Munoz & Lewinsohn, 1976)
                                                              Dysfunctional Attitudes Scales (Weissman & Beck, 1978)
                                                              The Perceived Competence Scale (Harter 1982)
Diagnostic variables                                          Major depression (RDC criteria using K-SADS)
                                                              Any non-affective comorbid disorder
                                                              Total number of all past diagnoses, both affective and non-affective
                                                              Double-depression
                                                              Duration of current depressive episodes
                                                              Total duration of all past depressive episodes
                                                              Age at onset of first depressive episode
                                                              Total number of suicide attempts
                                                              Beck Depression Inventory
Environmental variables                                       Pleasant Events Schedule (MacPhillamy & Lewinsohn, 1982)
                                                              Interpersonal Events Schedule (Ibid)
Parent conflict and family demographics                       Issues Checklist, Parent (Robin & Weiss, 1980)
                                                              Issues Checklist, Teen (Ibid)
                                                              Birth order
                                                              Living with parents (both, one, none)
                                                              Number of siblings
                                                              Parent’s marital status
                                                              Mother in mental health treatment
                                                              Family income
                                                              Socio-Economic Status
Treatment variables                                           Assigned treatment condition (with or without parental involvement)
                                                              Number of sessions attended
                                                              Percent of homework completed
Potential confounders: not stated
                                                            INTERNAL VALIDITY
Outcome measurement method [12]                                                   Comparison of study groups [14]               Blinding [15]
Recovered, based on no longer meeting RDC diagnosis (on K-SADS) at                Not stated                                    Not stated
posttreatment
Depressive symptoms on the BDI




776                                                                 Depression in adolescents and young adult
Measurement bias [16]                                                                Follow-up (ITT) [17]
Unlikely                                                                             Not stated
Overall quality assessment (descriptive) [18]. Poorly reported article – no description of population, no indication of     Quality
number who dropped out. Possible that the methods used were good, but not clear.                                            assessment: -
                                                                    RESULTS

Outcome [19] All four broad pretreatment variables were significant predictors of improvement


Univariate outcome                                      Correlation with recovery + significance [22]            Correlation with
                                                                                                                 posttreatment BDI +
                                                                                                                 significance [22]
Lower intake levels on the BDI                          r=0.46, p<0.005
Lower intake state anxiety                              r=0.41, p<0.01
Higher enjoyment of and frequency of pleasant           r=-0.51, p<0.005
activities
More rational thoughts on the Subjective Probability    r=0.56, p<0.001
Questionnaire
Dysfunctional Attitudes Scale                                                                                    r=0.33, p<0.05
Total number of all past diagnoses, both affective                                                               r=-0.39, p<0.01
and non-affective
Age at onset of first depressive episode                                                                         r=0.31, p<0.05
Issues checklist, Teen                                                                                           r=0.32, p<0.05
Living with parents (both, one, none)                                                                            r=0.30, p<0.05
Assigned treatment condition                                                                                     r=-2.8, p<0.05
Multi variate outcome                                   Measure of effect/effect size + 95% CI [22]
Intake BDI                                                                                                       β=0.49, p<0.001
Parent involvement in treatment                                                                                  β=-0.29, p<0.01
Age onset    1st   depressive episode                                                                            β=0.28, p<0.01
Greater number previous diagnosis                                                                                β=-0.26, p<0.05
Conclusion: Lower levels of depressive symptoms at posttreatment was associated with a lower levels of depressive symptoms at intake,
greater number of past psychiatric diagnoses, parent involved in treatment, and younger age of onset of first depressive episode
                                                              EXTERNAL VALIDITY

Generalisability: difficult to determine based on this article, as population was not described

Comments:




Depression in adolescents and young adults                                                                                        777
                                                                STUDY DETAILS
Reference [1] (Clarke et al 1999) Clarke, G. N., Rohde, P. et al (1999). 'Cognitive-behavioral treatment of adolescent depression: efficacy of
acute group treatment and booster sessions', J Am Acad Child Adolesc Psychiatry, 38 (3), 272-279.
Affiliation/source of funds [2] Kaiser Permanente Center for Health Research, Portland, Oregon, US and the Oregon Research Institute,
Eugene, US, Part funded by a NIMH grant.
Study design [3] RCT            Level of evidence [4] Interventional level II        Location/setting [5] Eugene and Portland Oregon, United
                                                                                     States
Intervention [6] 16 sessions of CBT over 8 weeks for           Comparator(s) [8] (2) Identical to group (1) plus supplemental 9 session parent
adolescents only (n=45) using CWD-A                            group (n=42), (3) waitlist control (n=36)
Selection criteria
Inclusion criteria – adolescents 14-18 years of age with current DSM-III-R diagnosis of major depressive disorder or dysthymia
Exclusion criteria –current mania, panic disorder, generalized anxiety disorder, conduct disorder, psychoactive substance abuse/dependence,
lifetime organic brain syndrome, mental retardation or schizophrenia, currently receiving other treatment for depression and unwilling to
discontinue or needed immediate acute treatment
Patient characteristics [10] 96 adolescents who completed the treatment were 70.8% female, and had a mean age of 16.2 years (SD≤1.3);
4.2% were not in school; 43.8% lived in 2-parent families and 27.7% had 1 or 2 parents with graduate or postgraduate education. 87.5% had
MDD, 46.9% had recurrent affective disorder, 23.6% had a current comorbid anxiety disorder. 73 had pure MDD, 12 had pure dysthymia and 11
had comorbid MDD/dysthymia
Intervention group – not independently stated
Comparator group(s) –not independently stated
Length of follow-up [11]          Outcome(s) measured [12] Primary – level of functioning using GAF; Secondary - recovery from depression
24 months                         using LIFE, HAM-D, K-SADS, BDI, and CBCL,
                                                             INTERNAL VALIDITY
Allocation [13]             Comparison of study           Blinding [15]                Treatment/                  Follow-up (ITT) [17]
Random, method not          groups [14]                   Interviewers were            measurement bias [16]       Intention to treat stated but
stated                      No differences on             blinded to participant’s     Standardised                no details given
                            demographics or               condition.                   questionnaires used so
                            baseline depression                                        measurement bias
                            variables                                                  unlikely
Overall quality assessment (descriptive) [18] good quality study
                                                                    RESULTS
Outcome                     Intervention group         Control group (2)               Control group (3)        Measure of effect/effect size
Acute Phase, pre-post       Adolescent only (A)        Adolescent + parent (AP)        Waitlist (WL)            RER planned comparison:
treatment continuous                                                                                            Group x Time significance
measures                                                                                                        A/AP vs WL (z); A vs AP (z)
                                                           Mean SD
Depressive symptoms             Mean SD                Pre 15.1±6.0                        Mean SD              1.10              0.03
on HAM-D
                            Pre 13.0±5.3               Post 6.7±7.1                    Pre 14.5±5.9
                            Post 4.6±4.8                                               Post 7.7±7.0


Depressive symptoms         Pre 26.5±9.4               Pre 26.4±8.7                    Pre 24.2±10.8            2.79**            0.63
on BDI                      Post 10.1±9.1              Post 13.3±10.9                  Post 16.0±11.2


Global functioning on       Pre 60.4±6.8               Pre 54.4±8.2                    Pre 58.3±7.2             2.44*           1.55
GAF                         Post 71.0±11.7             Post 69.9±14.9                  Post 64.5±11.8


Depressive symptoms         Pre 14.5±4.0               Pre 16.1±5.5                    Pre 14.9±4.9             1.72            0.75
on CBCL-Depression          Post 11.5±4.7              Post 11.7±6.7                   Post 9.0±5.9             *p<.05, **p=.01




778                                                                   Depression in adolescents and young adult
                            64.9% = 24/37             68.8% 22/32                  48.1% 13/27
                            The 2 active              The observed recovery
                            treatments had            proportions yielded an
                            significantly better      odds ratio of 2.15 (90%
                            outcomes compared         conf.int = 1.01-4.59)
                            with waitlist control     indicating treated
                            (x2[1,N=96]=2.81, 1-      participants were 2x as
                            tailedp <.05; Cohen’s     likely as those on the
                            h=0.38, a small to        waitlist to recover during
                            medium effect size        the acute phase

                            Annual (A)                Frequent (F)                 Booster (B)
                            (n=19)                    (n=10)                       (n=17)
                            Post 6.8±7.9              Post 3.5±3.9                 Post 3.9±3.1
                            12 mo 3.6±5.4             12 mo 0.5±1.6                12 mo 3.2±4.1
                            24 mo 3.3±5.3             24 mo 0.2±0.6                24 mo 1.1±1.9



                                                                                                            Planned comparison for the
Recovery rate                                                                                               acute phase analyses compared
                                                                                                            the 2 active treatments
                                                                                                            combined versus the waitlist and
                                                                                                            the A versus A+P conditions
                                                                                                            using 1-tailed test, with p<.05. All
                                                                                                            other analyses were 2-tailed with
                                                                                                            p<.05

Maintenance Phase,                                                                                          RER Planned comparison
continuous measures                                                                                         Group x time significance
Depressive symptoms                                                                                         A+F vs B (z). A vs F (z)
on HAM-D                                                                                                    0.98            0.37


Depressive symptoms         Post 13.5±11.5            Post 6.3±7.0                 Post 8.7±7.5             1.06             0.52
on BDI                      12 mo 11.1±12.9           12 mo 3.3±3.8                12 mo 8.1±7.9
                            24 mo 7.8±6.3             24 mo 1.3±2.6                24 mo 5.4±6.1

Global functioning on       Post 69.4±14.5            Post 77.0±8.0                Post 73.0±9.1            0.38            0.21
GAF                         12 mo 73.8±12.1           12 mo 80.7±6.8               12 mo 78.8±10.9
                            24 mo 75.7±11.3           24 mo 84.6 ±3.6              24 mo 82.7±8.8
Depressive symptoms         Post 8.5±5.8              Post 12.8±4.6                Post 12.1±4.5            1.45          3.37***
on CBCL-Depressions         12 mo 7.3±6.9             12 mo 6.1±4.9                12 mo 7.9 ±6.1
                            24 mo 8.9±7.4              24 mo 5.8±5.5               24 mo 5.3±4.1
                                                                                                            *p <.05, **p<.01, ***p<.0001

By 12 months 100% of
depressed adol.
randomly assigned to
the booster condition
had recovered versus
50% participants in the 2   Clinical importance (1-4) [26]                         Relevance (1-5) [27] Potential to reduce the recovery time
assessment-only                                                                    from, and reoccurrence of, a depressive episode
                            Booster sessions did not reduce relapse, however
conditions. (x2[1,
                            did accelerate remission in patients with depression
N=17]=3.86, p<.05).
                            at the end of the acute phase. Evidence of some
However by 24 months        benefit for relevant outcomes
the assessment only
groups had reached
90% recovery.
Any other adverse effects [28] none reported




Depression in adolescents and young adults                                                                                    779
                                                              EXTERNAL VALIDITY

Generalisability [29] likely to be generalisable to target population although exclusion criteria quite extensive

Applicability [30] the benefits appear to be in shortening the length of depressive episodes

Comments [31] parent involvement in treatment did not significantly enhance improvement however this was not the primary focus of the study
and attendance at parent groups was not ideal
CBCL-D= Child Behavior Checklist; CBT=Cognitive Behavioral Therapy; CWD-A= Coping With Depression Course; GAF= Global Assessment of
Functioning Scale; HAM-D=Hamilton Depression Rating Scale; K-SADS-E=Schedule for Affective Disorders and Schizophrenia for School-Age
Children-Epidemiologic Version; LIFE= Longitudinal Interval Follow-up Evaluations; MDD= Major Depressive Disorder;




780                                                                    Depression in adolescents and young adult
                                                                 STUDY DETAILS
Reference [1] (Clarke et al 2002) Clarke, G. N., Hornbrook, M. et al (2002). 'Group cognitive-behavioral treatment for depressed adolescent
offspring of depressed parents in a health maintenance organization', J Am Acad Child Adolesc Psychiatry, 41 (3), 305-313.
Affiliation/source of funds [2] Kaiser Permanente’s Center for Health Research, Portland OR, Oregan Research Institute, Eugene, Supported
by NIMH Grant
Study design [3] RCT         Level of evidence [4] Interventional level II       Location/setting [5] Kaiser Permanente Northwest HMO,
                                                                                 Portland OR
Intervention [6] CBT 16x2hr sessions over 8 weeks, led by             Comparator(s) [8] Usual Care Control Condition which comprised
Masters level therapists. Average attendance 10.1 sessions.           outpatient mental health speciality care visits, inpatient mental health day
Adolescents were taught relaxation skills, cognitive restructuring    and 135 days supply of psychotropic medications
techniques increasing the frequency of pleasant activities and        Sample size [9] n=47
communication and conflict-reduction techniques. Sample size
[7] n=41
Selection criteria; Adolescent (aged 13-18) offspring of parents treated for depression in a particular HMO and had been dispensed
antidepressants at least twice in the past 12 months or had at least two mental health visits (n=5954). Physician identified those deemed
appropriate for the study and 2995 letters were sent and respondent (n= 744) families then interviewed. 472 youths classified as highly
depressive, medium depression or low depression also known as resilient.
Inclusion criteria –Adolescents in the high depression group (n=116) with a current DSM-III-R diagnosis of major depressive disorder and/or
dysthymia became the focus of the study
Exclusion criteria –79 parent/youth dyads eliminated because parents did not have major depression
Patient characteristics [10] Intervention group –13-18 years old with DSM-III-R major depression,
Comparator group(s) – 13-18 year old with DSM-III-R major depression
Length of follow-up [11] 24 months                                    Outcome(s) measured [12] recovery from depression using depression
                                                                      assessment measures HAM-D, K-SAD, CES-D, GAF, and interviews
                                                               INTERNAL VALIDITY
Allocation [13]                      Comparison of study groups [14]                          Blinding        Treatment/        Follow-up (ITT)
Random assignment using              Did not differ on parent age or gender, youth age or     [15]            measureme         [17] 88 randomly
blocked procedure to ensure          gender, or youth baseline GAF, HAM-D, or CBCL-D          Assessors       nt bias [16]      assigned, 2 did not
that group assignments were          scores. Randomised youth had higher baseline             were            unlikely given    take part in any
never imbalanced. All subjects       CES-D scores (33.9 vs 29.1 p=.02) were on                blinded re      similarities      follow up interviews,
included – intent to treat design.   average 6 months older p=.001 and more likely to         experiment      between           2/6/13 did not
116 invited, 28 declined, 41 to      be female (68% vs 46% of non randomized pool             al condition    groups            participate in the
treatment group, 47 to control       p=≤.01)                                                  of subjects                       post
group                                                                                                                           treatment/12mth/24
                                                                                                                                mth respectively
Overall quality assessment (descriptive) [18] good quality study
                                                                     RESULTS
Outcome [19]          Intervention group [20]            Control group [21]                        Measure of effect/effect size [22]
                      (n=41)                             (n=47)
Depressive            Pre: 33.5±8.3                      Pre: 34.2±9.8                             Treatment by time           No. of sessions by
symptoms on           Post : 26.7±12.6                   Post: 29.3±12.8                           (main effect)               time, tx subjects
CES-D                 12 months: 22.4±9.2                12 months: 23.8±13.8                      F=0.42, p=0.52              (dose effect)
                      24 months: 24.3±11.6               24 months: 26.3±12.9                                                  F=0.04 p=0.84

Depressive            Pre:12.0±5.3                       Pre:11.4±5.0                              Treatment by time           No. of sessions by
symptoms on           Post: 5.5±5.2                      Post: 6.0±5.1                             (main effect)               time, tx subjects
HAM-D                 12 months: 4.3±4.2                 12 months: 3.3±5.0                        F=0.26, p=0.61              (dose effect)
                      24 months: 4.1±4.1                 24 months: 4.4±5.1                                                    F=1.13 p=0.29
Depressive            Pre:1.1±1.3                        Pre:1.0±1.3                               Treatment by time           No. of sessions by
symptoms on K-        Post: 0.6±1.2                      Post: 0.4±1.1                             (main effect)               time, tx subjects
SADS                  12 months: 0.1±0.6                 12 months: 0.2±0.6                        F=0.10, p=0.75              (dose effect)
                      24 months: 0.3±0.9                 24 months: 0.3±1.0                                                    F=0.46 p=0.50
Depressive            Pre: 9.6 ±5.3                      Pre: 9.3±5.7                              Treatment by time           No. of sessions by
symptoms on           Post: 10.2±5.8                     Post: 8.9±5.1                             (main effect)               time, tx subjects
CBCL-                 12 months: 8.2±6.4                 12 months: 8.4±5.4                        F=0.02, p=0.99              (dose effect)
Depression                                                                                                                     F=0.07 p=0.79
                      24 months: 8.4±7.4                 24 months: 8.0±5.5




  Depression in adolescents and young adults                                                                                          781
Global                Pre: 59.6±10.7                      Pre: 61.3±9.2                           Treatment by time           No. of sessions by
functioning on        Post: 66.8±12.5                     Post: 66.8±11.5                         (main effect)               time, tx subjects
GAF                   12 months: 74.6±12.9                12 months: 76.8±10.2                    F=0.16, p=0.69              (dose effect)
                      24 months: 73.9±12.4                24 months: 76.3±10.8                                                F=3.27 p=0.08



                      Clinical importance (1-4) [26] no significant differences found between     Relevance (1-5) [27]
                      groups before or after treatment
Any other adverse effects [28] none stated

                                                                  EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population

Applicability [30] recruitment using HMO contact with depressed parents may not be as easily achieved in the Australian setting

Comments [31] study found little benefit of CBT for adolescents with parents with depressive diagnosis

  * Table will be modified for studies regarding risk factors and the impact they have on outcomes
  CBLC-D= Child Behavior Checklist; CBT=Cognitive Behavioral Therapy; CES-D= Center for Epidemiologic Studies-Depression Scale; HAM-D=Hamilton
  Depression Rating Scale; K-SADS=Schedule for Affective Disorders and Schizophrenia for School-Age Children:




  782                                                                     Depression in adolescents and young adult
                                                              STUDY DETAILS
Reference [1] Clarke, G., Debar, L. et al (2005). 'A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed
adolescents receiving antidepressant medication', J Am Acad Child Adolesc Psychiatry, 44 (9), 888-898. (Clarke et al 2005)
Affiliation/source of funds [2] Kaiser Permanente Center for Health Research, Portland Oregon, US, Group Health Cooperative Center for
Health Studies, Seattle, US, supported by grants from the Agency for Healthcare Research and Quality and the Garfield Memorial Fund
Study design [3]        Level of evidence [4]                            Location/setting [5]
RCT                     Interventional level II                          Kaiser Permanente Northwest HMO, Portland Oregon, US
Intervention [6] CBT + TAU SSRIs (n=77)                                  Comparator(s) [8] TAU + SSRIs (n=75)
Comprised 5-9 x 60 minute sessions of acute-phase individual CBT,        All participants treated as usual including health care services or
ongoing therapist and PCP consultation and brief periodic telephone      medications provided by HMO and/or outside providers
contact during the 12 month follow-up period
Selection criteria - current research-ascertained DSM episode of major depression,
Inclusion criteria – Adolescents who constituted membership of the HMO, with current use of SSRIs, 12-18 years old,
Exclusion criteria – schizophrenia or significant developmental/intellectual disability
Patient characteristics [10] (n=152), 73.7% (n=112) reported significant levels of suicidal behaviour, 79% (n=120) female,
Intervention group – (n=77) mean age 15.29±1.62, 77.92% female, 12.99% minority,
Comparator group(s) – (n=75) mean age 15.32±1.60, 77.33% female, 15.07% minority,
Length of follow-up [11] 52 weeks             Outcome(s) measured [12] Primary – functioning using CGAS, SAS-SR, Secondary –
                                              depressive symptoms using K-SADS-PL, CES-D, HAM-D YSR-D and LIFE,
                                                           INTERNAL VALIDITY
Allocation [13]       Comparison of study groups         Blinding [15]               Treatment/                     Follow-up (ITT) [17]
Randomisation         [14]                               Blind interviewers          measurement bias [16]          Intent-to-treat from
using a blocked       No significant differences on      assessed adolescents        All participants treated       randomisation, completers
procedure, no         condition, gender, minority        and parents at baseline,    and measured the same          72.7% treatment group at
further details       status, and outcome measures       6, 12, 26, and 52 weeks,    except for intervention,       52 week follow-up, 77.3%
given                 however participants with no       baseline interview 60                                      control group at 52 week
                      follow-up assessments were         mins follow-up                                             follow-up
                      slightly older (p=.054)            interviews 45 mins,
Overall quality assessment (descriptive) [18] good quality study
                                                                   RESULTS

Outcome [19]            Intervention group [20]            Control group [21]                    Measure of effect/effect size [22]
Depressive              CBT + TAU SSRIS                    TAU +SSRIs control                    Treatment x Time p.07 F3.2 (for linear (time
symptoms using          Baseline       35.4±11.8           Baseline       33.7±9.3               x treatment) effect,
CES-D, mean (±SD)       6 week f/u     20.1±11.6           6 week f/u    19.6 0.2                effect size D 0.170 for the largest time x
                        12 week f/u    15.7±11.3           12 week f/u   16.6±9.6                treatment effect for the best-fitting of three
                                                                                                 models – linear, quadratic and cubic)
                        26 week f/u    13.7±11.5           26 week f/u   15.0±11.4
                        52 week f/u    11.5±11.0           52 week f/u   14.9±10.1
Depressive              CBT + TAU SSRIs                    TAU +SSRIs control                    Treatment x Time p .32 F 1.0 (for the
symptoms using          Baseline 21.1±6.8                  Baseline    21.8±5.8                  quadratic (time x time x treatment) effect)
HAM-D, mean (SD)        6 week f/u 11.9±7.6                6 week f/u 11.9±7.3                   Effect size D 0.054 for the largest time x
                        12 week f/u 8.2±6.6                12 week f/u 8.4±6.7                   treatment effect for the best-fitting of three
                                                                                                 models (linear, quadratic and cubic)
                        26 week f/u 6.5±6.7                26 week f/u 7.8±6.9
                        52 week f/u 4.9±7.1                52 week f/u 6.5±6.6
Depressive              CBT + TAU SSRIs                    TAU + SSRIs control                   zTreatment x Time p .11 F 2.51 for the
symptoms using          Baseline    16.5±4.8               Baseline    16.0 ±4.4                 linear (time x treatment) effect,
YSR-D, mean (SD)        6 week f/u 11.4±5.3                6 week f/u  10.6±4.4                  Effect size D 0.142 for the largest time x
                        12 week f/u 8.7±5.0                12 week f/u 8.7±5.1                   treatment effect for the best-fitting of three
                                                                                                 models (linear, quadratic and cubic)
                        26 week f/u 8.1±5.3                26 week f/u 8.2±4.6
                        52 week f/u 7.0±5.3                52 week f/u 8.4±4.8




Depression in adolescents and young adults                                                                                      783
Functioning using         CBT + TAU SSRIs                       TAU + SSRIs control                     Treatment x Time p .22 F 1.52 for the
CGAS, mean (SD)           Baseline    49.8±8.1                  Baseline    49.5±8.1                    largest time x treatment effect for the best-
                          6 week f/u 60.4±10.1                  6 week f/u  59.5±9.5                    fitting of three models (linear, quadratic and
                                                                                                        cubic)
                          12 week f/u 65.5±10.0                 12 week f/u 63.7±9.6
                                                                                                        Effect size D 0.090 for the largest time x
                          26 week f/u 68.8±8.4                  26 week f/u 66.6±8.7                    treatment effect for the best-fitting of three
                          52 week f/u 71.4±8.7                  52 week f/u 68.4±7.6                    models (linear, quadratic and cubic)
Survival analysis of                                                                                    Wilcoxon analysis (df=1, N=152, p=.36, X2
recovery from index                                                                                     =0.84, not significant at 52 week follow-up
depressive episodes
Cox regression                                                                                          No significant differences when comparisons
analyses                                                                                                for gender, age or severity at intake
                          Clinical importance (1-4) [26] significant reduction in use of TAU            Relevance (1-5) [27]
                          services in the CBT group particularly outpatient visits and days’            Benefit may not have been detected because
                          supply of medication, CBT advantage was primarily between 6 and               both treatments were highly effective, both
                          12 months follow-up rather than during acute phase                            control and treatment were active rather than
                                                                                                        control being waitlist/placebo
Any other adverse effects [28] none stated

                                                                EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population

Applicability [30] the CBT was only 5-9 sessions whereas studies showing greater CBT benefit have as many as 15 sessions, this suggests
that CBT must be of adequate duration to produce the benefit desired
Comments [31] TAU SSRIs treatment by clinicians in this HMO was reported as meeting or exceeding guidelines for youth depression
pharmacotherapy which may have led to superior outcomes for the control group also the treatment group received 20% less antidepressant
medication through the 1 year follow-up which may have masked the CBT benefit
CBT=Cognitive Behavioral Therapy; CES-D=Center for Epidemiological Studies-Depression Scale; CGAS=Children’s Global Adjustment Scale; HAM-
D=Hamilton Depression Rating Scale; HMO=Health Maintenance Organization; K-SADS-PL=Schedule for Affective Disorders and Schizophrenia for
School-Age Children-Present and Lifetime Version; LIFE=Longitudinal Interval Follow-up Evaluation; PCP=Primary Care Provider; SAS-SR=Social
Adjustment Scale-Self Report Version (range 1-5 with higher scores indicating worse functioning); SSRI=Selective Serotonin Reuptake Inhibitor;
TAU=Treatment As Usual; YSR-D=Youth Self-Report-Depression;




784                                                                      Depression in adolescents and young adult
                                                               STUDY DETAILS
Reference [1] (Curry et al 2006)
Curry, J., Rohde, P. et al (2006). 'Predictors and moderators of acute outcome in the Treatment for Adolescents with Depression Study (TADS)',
J Am Acad Child Adolesc Psychiatry, 45 (12), 1427-1439.
Affiliation/source of funds [2] National Institute of Mental Health
Supported by contract from National Institute of Mental Health to Duke University Medical Center, Eli Lilly provided fluoxetine and placebo
Study design [3]                                        Level of evidence [4]        Location/setting [5]
Prospective inception cohort (for prognosis)            II prognostic                13 clinical sites
Patient characteristics [10]                                                                    Sample size [7]
Published elsewhere                                                                             N = 439
                                                                                                 Length of follow-up [11]
Treatment conditions:                                                                            Treatment length = 12 weeks
COMB = Combined fluoxetine and CBT (N=107)
FLX = fluoxetine (N=109)
PBO = placebo (N=112)
CBT = cognitive behavioural therapy (N=111)
Selection criteria
Inclusion criteria : Adolescents who met DSM-IV criteria for major depressive disorder, with stable depressed mood and functional impairment
Exclusion criteria : Not stated
Prognostic factor(s):                              Data collection method
Demographics
 Gender
 Race                                              White, African American, Hispanic or other, collapsed into white and minority
 Age                                               In years
  Family Income                                    Gross family income over the past year using the Child and Adolescent Services Assessment
  Referral source                                  Responding to an advertisement or not
  Verbal intelligence                              Vocabulary and block designs subtests of the WISC-III
Severity markers
  Duration of episode                              Independent evaluator completed a Schedule for Affective Disorders and Schizophrenia for
                                                   School-Age Children Children-Present and Lifetime version with adolescent and parent (K-
                                                   SADS)
  Severity of depression                           Clinical Global Impression – Severity scale after the CDRS-R for symptoms in past week
  Functional impairment                            100 point Children’s Global Assessment Scale
  Suicidal ideation                                Total score from adolescent-report Suicidal Ideation Questionnaire – Jr High version
  Melancholic features                             5 items from CDRS-R corresponding to DSM-IV melancholic features
Comorbidity                                        Current diagnoses and total number of comorbid diagnoses based on the K-SADS – P/L
 Dysthymia
 Anxiety disorder
 Disruptive behaviour disorder
 No. of comoborbid diagnoses
Parental psychopathology                           Parents who attended baseline assessment completed the Beck Depression Inventory II
  Primary caregiver depression                     (BDI-II)
Psychosocial factors                               Adolescents and parents completed the Conflict Behaviour Questionnaire
  Parent-adolescent conflict
  Hopelessness                                     Beck Hopeless Scale completed by adolescent
  Cognitive distortions                            Adolescents completed Children’s Negative Cognitive Errors Questionnaire (CNCEQ,
                                                   Leitenberg et al 1986)
Treatment expectancy                               Before randomisation, a treatment expectancy form completed by adolescents and parents
  Patient expectation for assigned treatment       on 7 point Likert scale
  Parent expectation for assigned treatment
Potential confounders: Not stated
                                                             INTERNAL VALIDITY



Depression in adolescents and young adults                                                                                      785
Outcome measurement method [12]                 Comparison of study groups [14] No               Blinding [15]
Depressive symptoms using CDRS-R scores         significant differences between treatment        Outcome blinded to treatment condition. Not
post-treatment (12 weeks)                       groups                                           stated if blinded to predictive factors
Measurement bias [16]                           Follow-up (ITT) [17]
Unlikely                                        Regardless of treatment compliance. ITT analysis using predicted score generated through
                                                RRM adjusted for the fixed (treatment, time, treatment x time) and random (patient, pateitn x
                                                time, and site) effects.
Overall quality assessment (descriptive) [18] Good quality RCT, used to explore prognostic factors. Predictive             Quality
factors and outcome measurement well described and reliable. Used ITT approach.                                            assessment:
                                                                                                                           ++
                                                                  RESULTS

Outcome [19]
Predictors = main effect on outcome regardless of treatment condition; Moderators = effect varies depending on treatment condition
Univariate outcome                     Measure of effect/effect size [22]
                                       Variable (predictor)             Levels of depressive symptoms
Age                                    F(1,419)=7.09, p<0.01            aged 12-15, lower than aged 16-17 years
Duration (wk)                          F(1,419)=9.84, p<0.01            <40 wk lower than >40 wk
Severity (CGI-S)                       F(1,419)=73.35, p<0.001
Functioning (CGAS)                     F(1,419)=7.13, p<0.01            <51 higher than 51-100
Suicidal ideation (SIQ-Jr)             F(1,419)=12.04, p<0.001          <31 lower than >31
Melancholic features (CDRS-R)          F(1,408)=30.76, p<0.001          0 – 1 lower than 2 – 5
Comorbid anxiety                       F(1,418)=4.65, p<0.05            Absent lower than present
No. of comorbid diagnoses              F(1,417)=6.60, p<0.01            0-1 lower than >1
Hopelessness (BHS)                     F(1,407)=12.70, p<0.001          <9 lower than >9
Adolescent treatment expectancy        F(5,371)=3.17, p<0.01            low (-3 to +1) higher than high (+2 to +3)
Univariate outcome                     Variable x Treatment (moderator)
Family income (CASA)                   F(12, 362)=2.14, p<0.05       <$75,000/year, COMB and FLX equally effective, more effective than CBT
                                                                     and PBO which did not differ from each other
                                                                     >$75,000/year, COMB and FLX and CBT equally effective. COMB and
                                                                     CBT more effective than PBO, but FLX not more effective than PBO
Severity (CGI-S)                       F(3,419)=4.79, p<0.01         Lower baseline levels of severity: COMB better than FLX or CBT which
                                                                     did not differ. COMB and FLX better than PBO.
                                                                     Higher levels of severity: COMB and FLX equally effective, and better
                                                                     than PBO and CBT, which did not differ
Cognitive distortions (CNCEQ)          F(3,407)=2.95, p<0.05         Lower cognitive distortions: COMB or FLX equally effective, both better
                                                                     than CBT or PBO which did not differ.
                                                                     Higher cognitive distortions: COMB superior to FLX, which was superior to
                                                                     CBT. COMB and FLX superior to PBO.
Conclusion:

                                                              EXTERNAL VALIDITY

Generalisabilty:

Comments: Article clearly aims to be exploratory, rather than confirmatory
Those that were independent of treatment condition are discussed in “prognosis” section
Those that moderated treatment effects are also discussed in the pharmacotherapy and psychotherapy treatment sections.




786                                                                 Depression in adolescents and young adult
                                                                  STUDY DETAILS
Reference [1] (Curtis 1992)Curtis, S. E. (1992) In Psychology, Vol. Doctor of Philosophy Utah State University
Logan, pp. 97.
Affiliation/source of funds [2] Utah State University, Logan, no funding source identified
Study design [3] RCT                       Level of evidence [4] Interventional level II          Location/setting [5] Mountain Crest High School,
                                                                                                  Utah
Intervention [6] AWCDC 12 x 2hour sessions over an 8 week                  Comparator(s) [8] waitlist
period                                                                     Sample size [9] N=9
Sample size [7] N=10
Selection criteria
Inclusion criteria – Adolescents with diagnosis of DSM-III-R MDD, dysthymia or adjustment disorder with depressed mood
Exclusion criteria – bipolar
Patient characteristics [10] N=19, 17 females, 2 males, mean age 15.8 years
Intervention group – N=10, 8 females, 2 males, mean age 15.6 years
Comparator group(s) – N=9, 9 females, no males, mean age 16.1 years
Length of follow-up [11] length of treatment only                          Outcome(s) measured [12] Secondary – depressive symptoms using
                                                                           CAS, RADS and BDI
                                                                INTERNAL VALIDITY
Allocation [13]           Comparison of study           Blinding [15]         Treatment/ measurement          Follow-up (ITT) [17]
Randomisation not         groups [14]                   no                    bias [16]                       4 participants (2 from each group)
specified                 The waitlist group had                              Groups treated and              completed pre assessments but
                          no male participants                                measured the same               dropped out before post assessments
                          otherwise similar in all                            except for intervention
                          aspects
Overall quality assessment (descriptive) [18] good quality but small sample size

                                                                      RESULTS

Outcome [19]                     Intervention group [20]                   Control group [21]                           Measure of effect/effect
Depressive symptoms using        ACWDC                                     Waitlist                                     size [22]
BDI mean and SD                  Pre treatment 26.6±10.2                   Pre treatment 24.6±6.4
                                 Post treatment 8.5±10.3                   Post treatment 22.5±10.5                     p<.01
Depressive symptoms using        Pre treatment 19.7±5.3                    Pre treatment 21.6±4.8
CAS mean and SD                  Post treatment 4.7±4.6                    Post treatment 20.1±5.0                      p<.01


Depressive symptoms using        Pre treatment 56.1±13.4                   Pre treatment 61.0±3.8
RADS mean and SD                 Post treatment 29.4±22.2                  Post treatment 56.7±14.2
                                 Clinical importance (1-4) [26] benefit of early intervention in the school             Relevance (1-5) [27]
                                 setting
Any other adverse effects [28] none stated

                                                               EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population

Applicability [30] benefits outweigh harms

Comments [31] small sample size and high proportion of female participants

ACWDC= Adolescent Coping with Depression Course; BDI= Beck Depression Inventory (range 0-39 with higher scores indicating greater number of symptoms of
depression); CAS= Child Assessment Schedule; RADS= Reynolds Adolescent Depression Scale;




Depression in adolescents and young adults                                                                                           787
                                                                STUDY DETAILS
Reference [1] (Diamond et al 2002) Diamond, G. S., Reis, B. F. et al (2002). 'Attachment-based family therapy for depressed adolescents: a
treatment development study', J Am Acad Child Adolesc Psychiatry
41 (10), 1190-1196.
Affiliation/source of funds [2] University of Pennsylvania School of Medicine, Philadelphia, Ben-Gurion University of the Negev, Beer-Sheva,
Israel, MCP Hahnemann University , Philadelphia, Funded by the National Alliance of Research on Schizophrenia and Depression, the
American Suicide Foundation and NIMH Grant
Study design [3] RCT             Level of evidence [4] Interventional level II       Location/setting [5] Philadelphia ,US
Intervention [6] ABFT 60-90 mins per week for 12 weeks,                   Comparator(s) [8] waitlist, weekly 15 min phone call to monitor for
doctoral/masters level therapist, learning 5 tasks to repair              potential clinical deterioration with a BDI
attachment and promote autonomy                                           Sample size [9] n=16
Sample size [7] n=16
Selection criteria
Inclusion criteria –DSM-III-R diagnosis of major depression, 13-17 years of age, primary carer willing to participate, had a BDI ≥16
Exclusion criteria – BDI ≤16, receiving antidepressant medication or psychotherapy, had >13 days of substance use in the previous 90 days,
had psychotic features, failure to meet criteria for MDD,
Patient characteristics [10] mean age 14.9 years (±SD 1.5), 78% (n=25) female, 69% (n=22) African American, 31% (n=10) white, 80% from
single parent families, 69% reported annual income ≤$30,000 and 34% ≤ $20,000; 19% had unwanted sexual experiences, had family
members using drugs or alcohol,
Intervention group – not separately specified
Comparator group(s) – not separately specified
Length of follow-up [11] 6 months post treatment           Outcome(s) measured [12] Primary - improved attachment,
                                                           Secondary - reduced suicide ideation and reduction in depressive symptomsusing; K-
                                                           SADS-P, HAM-D, BDI, SIQ, IPPA,
                                                               INTERNAL VALIDITY
Allocation [13]      Comparison of study groups            Blinding         Treatment/                  Follow-up (ITT) [17]
Randomisation        [14]                                  [15]             measurement bias [16]       Of the 16 participants in the waitlist
method not           No significant differences in pre     None stated      Groups likely treated       group, 7 no longer met the criteria for
stated               treatment severity or                                  and measured the same       MDD before receiving treatment and one
                     demographics of groups                                 except for intervention     dropped out leaving 8 who were
                                                                                                        subsequently treated with ABFT
Overall quality assessment (descriptive) [18] small sample size and the waitlist group commenced treatment after only 6 weeks of waiting
while the treatment group received 12 weeks of treatment, low attrition levels and reasonable attendances, average quality study
                                                                    RESULTS
Outcome [19]                     Intervention group [20]        Control group [21]          Measure of                   Benefits (NNT) [23]
                                 ABFT                           Waitlist                    effect/effect size [22]      Combined sample of 24
Depressive symptoms using                Mean SD                       Mean SD              Significant condition-by-    treated with ABFT 83%
BDI                                                                                         time interaction in          no longer met MDD
                                                                                            depressive symptoms          criteria at post treatment,
                                 Pre tx 23.8±7.4                Pre tx 8.0±7.1              (F 1,28 =9.3, p=.005,        paired t-test
                                 6 weeks 11.1±8.8                                           effect size [ES]=1.21)       demonstrated significant
                                 Post tx 10.4±9.8               Post tx 18.5±11.1           also higher levels of        change in 8 of 11
                                                                                            attachment to their          variables (p values
                                                                                            mothers (F 1,24 =3.6,        ≤.0005)
                                                                                            p=.07, ES=0.63), lower
                                                                                            levels of suicide ideation
                                                                                            (F 1,28 =3.15, p=.09,
                                                                                            ES=0.52), significant
Depressive symptoms using        ABFT                           Waitlist                    difference at 6 weeks
HAM-D                                                                                       between BDI ≤9 of
                                 Pre tx 20.1±5.6                Pre tx 17.1±7.0
                                                                                            ABFT (62%) and waitlist
                                 Post tx 10.3±8.7               Post tx 15.3±6.7            (19%) (X2 1 =6.37, p=.01

Family functioning using         ABFT                           Waitlist
IPPA                             Pre tx 80.1±22.0               Pre tx 80.7±19.0
                                 Post tx 90.4±20.2              Post tx 76.8±22.6




788                                                                   Depression in adolescents and young adult
Suicide ideation using SIQ       ABFT                            Waitlist
                                 Pre tx 34.2±21.8                Pre tx 30.0±19.3
                                 Post tx 21.0±16.6               Post tx 28.3±22.0
                                 Clinical importance (1-4) [26]                                Relevance (1-5) [27]
                                 Patients treated with ABFT showed significant reduced         Evidence of an effect on patient-relevant clinical
                                 rates and severity of depression, and almost significant      outcome
                                 reduced suicide ideation and improved attachment,
                                 rates of no MDD at end of treatment are equivalent or
                                 higher than other psychosocial treatments
Any other adverse effects [28] none stated

                                                               EXTERNAL VALIDITY

Generalisability [29] high proportion of low income African American females not sure if generalisable to Australian population

Applicability [30] Evidence of benefit in strengthening adolescent attachment to parents and reducing depressive symptoms

Comments [31]

ABFT=Attachment-based Family Therapy; BDI=Beck Depression Inventory (range 0-39 with higher scores indicating greater number of symptoms of
depression); HAM-D=Hamilton Depression Rating Scale; IPPA= Inventory of Parent and Peer Attachment; K-SADS-P=Schedule for Affective Disorders and
Schizophrenia for School-Age Children-Present Episode version; MDD=Major Depressive Disorder; SIQ= Suicide Ideations Questionnaire,




Depression in adolescents and young adults                                                                                           789
                                                         STUDY DETAILS
Reference [1] Eskin, M., Ertekin, K. & Demir, H. (2008). 'Efficacy of a problem-solving therapy for depression and suicide potential
in adolescents and young adults', Cognitive Therapy and Research, 32 (2), 227-245.

Affiliation/source of funds [2]Department of Psychiatry, School of Medicine, Adnan Menderes University, Turkey; NP Hospital,
Istanbul, Turkey; Middle East Technical University Health Center, Ankara, Turkey
Study design [3] RCT                         Level of evidence [4] Interventional      Location/setting [5]
                                             level II                                  Adnan Menderes University School of
                                                                                       Medicine and Health Center of the
                                                                                       Middle East Technical University,
                                                                                       Turkey.
Intervention [6]                                                   Comparator(s) [8] Waiting list
Individual problem solving therapy sessions provided weekly
for 6 weeks. Sessions were as described below:                     Sample size [9] N=26
      -     Definition of problems
      -     Goal setting
      -     Generating alternative solutions
      -     Decision making
      -     Solution implementation
      -     Assessment and verification
Sample size [7] N=27
Selection criteria
Inclusion criteria – None reported

Exclusion criteria – Students who did not meet the DSM-IV criteria for major depression; students who were currently under
medical treatment, those who were psychotic or had bipolar illness, and those who did not have their parent’s consent.

Patient characteristics [10]
Intervention group – Male (n=7, 26%), secondary school n=13 (48%), university n=14 (52%), background – urban (n=22, 82%) or
rural (n=5, 19%), perceived family income – low (n=1, 4%) medium (n=26, 96%) high (n=0,), mean age = 19.0 ± 3.2 years; mean
number of siblings = 1.7± 1.8; maternal education (mean number of school years) = 10.1 ± 4.3; paternal education (mean number
of school years) = 11.5 ± 4.5

Comparator group(s) – Male (n=7, 37%), secondary school n=11(58%), university n=8 (42%), background – urban (n=13, 68%)
or rural (n=6, 32%), perceived family income – low (n=3, 16%) medium (n=15, 79%) high (n=1, 5%), mean age = 19.3 ± 3.7 years;
mean number of siblings = 2.3± 2.6; maternal education (mean number of school years) = 6.6 ± 5.1; paternal education (mean
number of school years) = 9.3 ± 5.0

Length of follow-up [11] 12 months                                 Outcome(s) measured [12]
                                                                   Primary – remission of depression (BDI and HAM-D);
                                                                   functioning measured by PSI and SIB
                                                                   Secondary – depressive symptoms measured by BDI and
                                                                   HAM-D, SPS, RSES and TAS
INTERNAL VALIDITY
Allocation [13]            Comparison of study        Blinding [15]              Treatment/                 Follow-up (ITT) [17]
Method of                  groups [14]                No blinding was            measurement bias           Per protocol analysis
randomisation not          There were some            reported for               [16]                       Completion of study:
reported                   differences at baseline    participants or            All subjects were          PST group: 27/27
                           between two groups:        outcome assessment.        assessed in the same       (100%)
                           Maternal education                                    way but lack of blinding   Waiting list: 19/26
                           was greater in PST                                    has increased the          (73%)
                           group than control                                    potential for              Follow up of PST
                           (p<0.05); paternal                                    measurement bias.          group: 22/27 (82%)
                           education was greater
                           in university students                                                           No difference in
                           than high school                                                                 demographics and
                           students (p<0.005);                                                              baseline scores were
                           although not reported                                                            found between those
                           as statistically                                                                 who completed the
                           significant there were                                                           study in waiting list
                           also differences in the                                                          group and those who
                           proportion of perceived                                                          dropped out.
                           low and middle income
                           families, and urban
                           and rural backgrounds.



790                                                                  Depression in adolescents and young adult
Overall quality assessment (descriptive) [18]
Average quality study – difficult to assess if the differences in groups at baseline were a result of poor randomisation or due to
chance.
RESULTS

Outcome [19]               Intervention group          Control group [21]          Measure of effect/effect size [22]
                           [20]
                                                                                   95% CI [25]

Recovery - BDI             Recovered (BDI, 0-9):       Recovered (BDI, 0-9):       �������� 2 (recovered + partial v not recovered) = 19.3,
                           14/27 (51.9%)               0/19 (0%)                   d.f. = 2, p<0.0001
                           Partially recovered         Partially recovered
                           (BDI, 10-15): 7/27          (BDI, 10-15): 3/19
                           (25.9%)                     (15.8%)
                           Not recovered               Not recovered
                           (BDI≥16): 6/27              (BDI≥16): 16/19

                                                                                   �������� 2 (recovered + partial v not recovered) = 31.1,
                           (22.2%)                     (84.2%)
Recovery - HAM-D           Recovered (HAM-D, 0-        Recovered (HAM-D, 0-
                           7): 22/27 (81.5%)           7): 1/19 (5.3%)             d.f. = 2, p<0.0001
                           Partially recovered         Partially recovered
                           (HAM-D, 8-12): 4/27         (HAM-D, 8-12): 3/19
                           (14.8%)                     (15.8%)
                           Not recovered (HAM-         Not recovered (HAM-
                           D≥13): 1/27 (3.7%)          D≥13): 15/19 (78.9%)
 Depressive symptoms       Pre-treatment:              Pre-waiting:                Repeated measures ANOVA:
- BDI                      26.7 ± 9.4                  28.0± 9.0                   Condition (PST or WL) v time: F(1,42) = 10.3,
                           Post-treatment:             Post-waiting:               p<0.001
                           10.7 ± 10.4                 22.0 ± 5.5                  Time (pre- and post- therapy): F(1,42) = 43.8,
                                                                                   p<0.0001
                                                                                   Condition (PST or WCL): F(1,42)) = 9.7, p<0.01
                                                                                   Group (High school or University): F(1,42) = 20.3,
                                                                                   p<0.0001

Depressive symptoms        Pre-treatment:              Pre-waiting:                Repeated measures ANOVA:
- HAM-D                    16.1 ± 6.6                  17.8± 5.5                   Condition (PST or WL) v time: F(1,42) = 37.7,
                           Post-treatment:             Post-waiting:               p<0.0001
                           4.3 ± 3.3                   16.6 ± 5.7                  Time (pre- and post- therapy): F(1,42) = 55.7,
                                                                                   p<0.0001
                                                                                   Condition (PST or WCL): F(1,42)) = 39.3,
                                                                                   p<0.0001
                                                                                   Group (High school or University): F(1,42) = 9.3,
                                                                                   p<0.01

Depressive symptoms        Pre-treatment:              Pre-waiting:                Repeated measures ANOVA:
- SPS                      84.1 ± 15.1                 77.9± 16.4                  Condition (PST or WL) v time: F(1,42) = 7.3,
                           Post-treatment:             Post-waiting:               p<0.05
                           71.9 ± 15.5                 75.2 ± 14.9                 Time (pre- and post- therapy): F(1,42) = 16.3,
                                                                                   p<0.0001
                                                                                   Group (High school or University): F(1,42) = 16.7,
                                                                                   p<0.0001

12 month follow-up         BDI: 7.6 ± 7.3              Data not collected          BDI - follow-up v pre-treatment:
                           BDI (university): 9.9 ±                                 Z=4.1, p<0.0001
                           7.0                                                     BDI - follow-up v post-treatment:
                           BDI (high school): 5.6                                  Z=1.6, p>0.05
                           ± 7.4                                                   BDI – university v high school a:
                           HAM-D: 3.7 ± 1.9                                        Z=2.0, p<0.05
                           HAM-D (university):2.6                                  HAM-D - follow-up v pre-treatment:
                           ± 1.5                                                   Z=4.1, p<0.0001
                           HAM-D (high                                             HAM-D - follow-up v post-treatment:
                           school):4.9 ± 1.7                                       Z=0.1, p>0.05
                                                                                   HAM-D – university v high school:
                                                                                   Z=2.6, p<0.05

                                                                                   a Text of article indicated that mean university
                                                                                   follow-up score was less than the mean follow-up
                                                                                   score for high school students



Depression in adolescents and young adults                                                                                           791
12 month follow-up          PSI: 88.6 ±15.6              Data not collected           PSI - follow-up v pre-treatment:
                            PSI (university): 90.4 ±                                  Z=3.7, p<0.0001
                            8.2                                                       PSI - follow-up v post-treatment:
                            PSI (High school): 86.1                                   Z=2.0, p<0.05
                            ± 18.7                                                    PSI – university v high school:
                                                                                      Z=1.1, p>0.05

                                                                                      PSI difference v BDI follow-up: �������� = - 0.41, n=22,
                                                                                      Pearson’s correlation coefficient:


                                                                                      PSI difference v HAM-D follow-up: �������� = - 0.26,
                                                                                      p<0.05 (one-tailed)

                                                                                      n=22, p>0.05 (one-tailed)
                            Clinical importance (1-4) [26]                            Relevance (1-5) [27]

Any other adverse effects [28]
No adverse events were reported
EXTERNAL VALIDITY

Generalisabilty [29]
There may be limited generalisability to patients who have not attended university
Applicability [30]
Potential benefits are likely to outweigh potential harms.
Comments [31]
PST may help improve depressive symptoms and decrease suicide potential, particularly in university students. Effect on
depressive symptoms appears to last at least 12 months.
BDI = Beck Depression Inventory; SPS = suicide probability scale; PSI = problem solving inventory; SIB = scale for interpersonal behaviour; RSES =
Rosenberg self-esteem scale; TAS = therapeutic alliance scale; PST = problem solving therapy; HAM-D = Hamilton Depression Rating Scale; WL = waiting
list




792                                                                       Depression in adolescents and young adult
                                                                STUDY DETAILS
Reference [1] (Feeny et al 2006) Feeny, N. C., Danielson, C. K. et al (2006). 'Cognitive-behavioral therapy for bipolar disorders in adolescents:
a pilot study', Bipolar Disord, 8 (5 Pt 1), 508-515.
Affiliation/source of funds [2] Department of Psychiatry, Case Western Reserve, University School of Medicine, University Hospital of
Cleveland, Department of Psychiatry & Behavioral Sciences, Medical University of South Carolina, Charleston, Children’s Hospital of
Philadelphia, Philadelphia, funding support from a Clinical Research Center Grant from the Stanley Medical Research Institute
Study design [3] Cohort                Level of evidence [4] III-2                Location/setting [5] Adolescent Psychiatry Clinic


Intervention [6] CBT for 12 weekly sessions then an 8 week               Comparator(s) [8] historical control group
follow-up
Sample size [7] N=8                                                    Sample size [9] N=8
Selection criteria Adolescents age 10 – 17 years attending Adolescent Psychiatry Clinic and on stable medication
Inclusion criteria - DSM-IV diagnosis of BP I, BP II or BP NOS or cyclothymia, must have experienced at least one mood episode in previous 6
months and be stable of medication (no changes in previous 3 months)
Exclusion criteria – unwilling or unable to remain on stable medication for duration of treatment, actively suicidal or psychotic, or history of
mental retardation or pervasive developmental disorder
Patient characteristics [10]
Intervention group – N=8 mean age 14±1.4, 50% male,
Comparator group(s) – N=8 mean age 14±2.5, 40% male,
Length of follow-up [11] 8 weeks after completion of treatment           Outcome(s) measured [12] Secondary - depressive symptoms using
                                                                         K-SADS-PL, IDS, GBI, Mania using YMRS, GBI

                                                             INTERNAL VALIDITY
Allocation [13]             Comparison of study          Blinding [15]                 Treatment/                     Follow-up (ITT) [17]
Not randomised,             groups [14]                  no                            measurement bias [16]          no
matched historical          Controls matched for                                       Control information was
controls from population    age and diagnosis                                          accessed from medical
of adolescents attending                                                               charts and had no
the same clinic                                                                        contact with the study
                                                                                       team
Overall quality assessment (descriptive) [18] average quality

                                                                     RESULTS

Outcome [19]                Intervention group [20]           Control group [21]                Measure of effect/effect size [22]
                            CBT N=8                           Control N=8
Symptoms of                 Pretreatment 15.4±9.9             Pretreatment 3.4±8.2              Between group ES
Depression using IDS        Posttreatment 10.7±9.2            Posttreatment 4.0±7.9             Pre-post 0.90
mean and SD                 Follow-up      12.6±5.4           Follow-up      2.9±5.0            Pre-FU 1.6
                                                                                                Post intervention F(1,8)=1.96, p=ns
                                                                                                Follow-up F (1,8) =5.11. p=0.05
Symptoms of Mania           Pretreatment      8.8±9.0         Pretreatment 10.3±11.7            Between group ES
using YMRS                  Posttreatment     4.4±5.3         Posttreatment 14.7±11.2           Pre-post 0.62
                            Follow-up         6.0±4.9         Follow-up      8.1±6.4            Pre-FU 0.00
                                                                                                Post intervention F(1,8)=0.93, p=ns
                                                                                                Follow-up F (1,8) = 0.07, ns
Depressive symptoms         Pretreatment 79.2±27.6                                              Effect size
using GBI mean and SD       Posttreatment 53.0±9.2                                              Decline in depressive symptoms pre-post
                            Follow-up     66.0±18.4                                             [t(4)=2.43,ns, d=1.09]
                                                                                                Decline in depressive symptoms pre-FU [t
                                                                                                (5)=1.26, ns, d=1.13]
Manic symptoms using        Pretreatment 41.0±9.9                                               Effect size
GBI mean and SD             Posttreatment 32.4±5.4                                              Decline in manic symptoms pre-post [t(4)=1.76,
                            Follow-up     39.3±11.3                                             ns, d=0.79]
                                                                                                Decline in manic pre-follow-up          [t
                                                                                                (5)=0.28, ns, d=0.25]




Depression in adolescents and young adults                                                                                        793
                              Clinical importance (1-4) [26]                                       Relevance (1-5) [27]

Any other adverse effects [28] none stated

                                                               EXTERNAL VALIDITY

Generalisability [29] small sample size and primarily Caucasian middle class, however likely generalisable to similar population

Applicability [30] benefits outweigh harms

Comments [31]

BP=Bipolar; CBT=Cognitive Behavioral Therapy; GBI=General Behavior Inventory; IDS=Inventory of Depressive Symptoms; K-SADS-PL=Schedule for
Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version; NOS=Not Otherwise Specified; YMRS=Young Mania Rating
Scale;




794                                                                     Depression in adolescents and young adult
                                                                     STUDY DETAILS
Reference [1] (Fine et al 1991) Fine, S., Forth, A. et al (1991). 'Group therapy for adolescent depressive disorder: a comparison of social skills
and therapeutic support', J Am Acad Child Adolesc Psychiatry 30 (1), 79-85.
Affiliation/source of funds [2] University of British Columbia, Vancouver, Canada, Funded by B.C. Health Care Foundation Grant
Study design [3] Pseudo randomized                Level of evidence [4] III           Location/setting [5] Vancouver General Hospital
Intervention [6] 12 week Therapeutic Support Group                            Comparator(s) [8] 12 week Social Skills Group
Sample size [7] TSG (n=36)                                                    Sample size [9] SSG (n=30)
Selection criteria: adolescents referred to the child and adolescent psychiatry outpatient department of Vancouver General Hosp
Inclusion criteria – 13-17 years of age, with current DSM-III-R major depressive episode or dysthmyia disorder
Exclusion criteria – neurological damage, borderline intelligence or below, younger than 13 or older than 17 years of age,
Patient characteristics [10] 88% (n=58) with depression, 12% )n=8) with dysthmyia, 77% white, 9% North American Indian, 9% Asian, 5%
mixed descent, 83% female, age 13-17 years (X=15.1±1.2), education from grade 7-12 (X=9.7±1.2)
Intervention group – not specified separately
Comparator group(s) – not specified separately
Length of follow-up [11] 9 months                           Outcome(s) measured [12] Secondary - reduction in depressive symptoms using CDI,
                                                            K-SADS-PE,
                                                                   INTERNAL VALIDITY
Allocation [13]                              Comparison of            Blinding [15]        Treatment/                  Follow-up (ITT) [17] 33% (n=19)
Pseudo randomised according to               study groups [14]        Not stated           measurement bias            did not complete treatment, a
time of presentation at hospital,            No differences in                             [16] Groups likely          further 7 did not complete follow up
assigned to whichever group                  baseline variables                            treated and measured        assessments leaving TSG (n=23)
currently about to commence                  or demographics                               the same except for         and SSG (n=17)
                                                                                           intervention
Overall quality assessment (descriptive) [18] small numbers and pseudo randomisation, otherwise good quality study

                                                                         RESULTS

Outcome [19]               Intervention group [20]        Control group [21]               Measure of effect/effect size         Benefits (NNT) [23]
                           TSG Mean and SD                SSG Mean and SD                  [22]
Depressive                                                                                                                       More rapid reduction in
symptoms using K-          Pre tx 40.44±5.16                                               K-SADS, F (1,46) =6.73 p <            depressive symptoms in
SAD-PE                     Post tx 24.00±6.97             Pre tx 38.15±7.94                0.01                                  the TSG group
                                                                                                                                 immediately after
                           9 month f/up                   Post tx 28.15±8.92                                                     treatment
                           19.04±6.87                     9 month f/up
                                                          20.65±8.36
Depressive                 TSG Mean and SD                SSG Mean and SD
symptoms using CDI         Pre tx 20.04±7.01              Pre tx 20.30±8.22                CDI F (1,46) = 3.38, p < 0.10
                           Post tx 14.74±6.76             Post tx 18.40±7.31
                           9 month f/up                   9 month f/up
                           11.91±8.66                     10.71±8.19
                           Clinical importance (1-4) [26]                                  Relevance (1-5) [27]
                           Both treatments were effective in the long term
                           however TSG had greater immediate impact after
                           treatment
Any other adverse effects [28] none stated
                                                                  EXTERNAL VALIDITY
Generalisability [29] likely generalisable to target population
Applicability [30] benefits outweigh harms
Comments [31] immediate effect for TSG greater however by 9 month follow up the SSG group had caught up
CBCQ=Cognitive Bias Questionnaire for Children; CDI=Child Depression Inventory (self report - range 0-54 with higher scores indicating greater number of
symptoms; GCQ= Group Climate Questionnaire; K-SADS=Kiddie Schedule for Affective Disorders and Schizophrenia; OSQI=the Offer Self Image
Questionnaire;




Depression in adolescents and young adults                                                                                                  795
                                                                     STUDY DETAILS
Reference [1] (Goodyer et al 2007)
Goodyer, I., Dubicka, B. et al (2007). 'Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive
behaviour therapy in adolescents with major depression: randomised controlled trial', Bmj, 335 (7611), 142.
(refer to (Byford et al 2007))
Affiliation/source of funds [2] Cambridge University, University of Manchester, Sheffield University, Center for Economics of Mental Health,
Cambridgeshire Primary Care, Thorn Road Clinic, Booth Hall Children’s Hospital, and Royal Manchester Children’s Hospital, United Kingdom
Supported by NHS Health Technology Assessment (HTA) Programme, Central Manchester and Manchester Children’s University Hospitals
NHS Trust, and the Cambridge and Peterborough Mental Health Trust.
Study design [3]                    Level of evidence [4]                      Location/setting [5]
Pseudo-RCT                          Interventional level III-1                 6 specialist CAMHS services in Manchester and Cambridge, United
                                                                               Kingdom
                                                                               Autumn 2000 – Autumn 2004
Intervention [6] SSRI:                                                         Comparator(s) [8] SSRI plus CBT:
Fluoxetine 10 mg/day for 1 week, 20 mg/day for 5 weeks, increased in           SSRI treatment as previously described
steps to 60 mg/day by 12 weeks if there was no response.                       CBT: 19 sessions, weekly for 12 weeks, fortnightly for 12 weeks
If fluoxetine was ineffective or caused side effects, other SSRIs were         Provided by psychiatrists or psychologists with previous CBT
considered. Those taking a different SSRI at randomisation continued           experience.
with their prescription, and if ineffective, the dose was increased, or        Focus on depressive symptoms, as well as comorbidities.
changed to fluoxetine.                                                         Engagement and goal setting, emotional recognition, self monitoring,
Offered 9 outpatient sessions of usual care over 28 weeks                      self reinforcement and activity scheduling, challenging negative
(psychoeducation, parental support, problem solving, attention to              thinking and cognitive restructuring, social problem solving and
comorbidity, and liaison with other agencies).                                 communication skills.
Sample size [7] 103                                                            Sample size [9] 105


Selection criteria
Inclusion criteria – Major or probably major depression (four symptoms with psychosocial impairment), aged 11 – 17 years with a score of 7 or
more on the Health of the Nation outcome scale for children and adolescents, indicating moderate to severe difficulties. People with active
suicidal intent, self harm, depressive psychosis, or conduct disorder were included.
Exclusion criteria – Schizophrenia or bipolar disorder, need for immediate admission, pregnancy or unreliable use of contraception, global
learning disability, prior sensitivity or allergy to an SSRI, medication that could interact with SSRI, medical contraindication, and previous
combined treatment with an SSRI and CBT with no effect.
Patient characteristics [10]
Intervention group –Median age = 14 years, 27% male, 56% with CGAS>40, 48% with comorbid social phobia, 36% with obsessive
compulsive disorder, 35% with PTSD, 28% with agoraphobia
Comparator group(s) – Median age = 14 years, 25% male, 47% with CGAS>40, 41% with comorbid social phobia, 40% with obsessive
compulsive disorder, 40% with PTSD, 34% with agoraphobia
Length of follow-up [11] Length of treatment:       Outcome(s) measured [12] Primary –global functioning on global assessment scale
28 weeks                                            (CGAS), clinical global impression improvement scale (CGI-I) and Health of the National
                                                    outcome scale (HoNos)
                                                    Secondary - depressive symptoms on CDRS-R, suicidality from K-SADS-PL depression
                                                    section
                                                                  INTERNAL VALIDITY
Allocation [13]               Comparison of study                Blinding [15]               Treatment/                    Follow-up (ITT) [17]
Stochastic minimisation       groups [14]                        Research assistants blind   measurement bias [16]         No, “ITT subject to the
balancing for severity,       No significant differences         to treatment allocation     Likely controlled for         availability of data”
centre, sex, concurrent       between groups at                  assessed outcomes
comorbid conduct              baseline, although SSRI +
disorder, and age.            CBT group had slightly
Allocation occured using      more comorbidities
independent telephone
centre.
Overall quality assessment (descriptive) [18] Average quality study


                                                                        RESULTS
Mean daily dose (for flexible dose studies): Fluoxetine: 30 mg/day in both groups




796                                                                       Depression in adolescents and young adult
Outcome [19]                Intervention group [20]      Control group [21] SSRI      Measure of effect/effect size [22]
                            SSRI                         + CBT
global functioning on       Pre: 40.3±6.3 (n=103)        Pre: 41.6±6.0 (n=105)        Time x Treatment interaction (random effects model)
global assessment scale     Post: 57.8±14.5 (n=94)       Post: 57.2±16.4 (n=98)       -0.03 [95%CI -0.22, 0.16) p=0.76
(CGAS)
Response on CGI (% 1:       57/94 (60.6%)                52/98 (53.1%)
very much improved or 2:
much improved)
Health of the National      Pre: 25.5±5.6 (n=103)        Pre: 25.1±5.5 (n=105)        Time x Treatment interaction (random effects model)
outcome scale (HoNos)       Post: 14.5±8.3 (n=95)        Post: 15.4±8.6 (n=98)        0.05 [95%CI -0.06, 0.16] p=0.38

Depressive symptoms on      Pre: 75.3±6.7 (n=103)        Pre: 75.1±6.7 (n=105)        Time x Treatment interaction (random effects model)
CDRS-R                      Post: 55.8±12.7 (n=94)       Post: 57.3±13.5 (n=98)       -0.02 [95%CI -0.19, 0.14] p=0.79
Proportion with suicidal    Pre: 44/103 (42.7%)          Pre: 40/105 (38.1%)          Time x Treatment interaction (random effects model)
ideation ( from K-SADS-     Post: 9/94 (9.6%)            Post: 13/98 (13.3%)          1.05 [95%CI 0.99, 1.12], p=0.13
PL depression section)
Proportion having           Pre: 21/103 (20.4%)          Pre: 13/105 (12.4%)          Time x Treatment interaction (random effects model)
attempted suicide (from     Post: 6/94 (6.4%)            Post: 7/98 (7.1%)            1.02 [95%CI 0.95, 1.10], p=0.54
K-SADS-PL depression
section)

                            Clinical importance (1-4) [26]

Any other adverse effects [28] SSRI alone: 61/103 (59%) reported side effects, and 65/105 (62%) in CBT + SSRI group (adjusted odds ratio
1.05, 95%CI 0.58, 1.91, p=0.87)
1 severe adverse events – a fit possibly related to SSRI (in SSRI alone group)
Most common side effects: headaches, nausea, tiredness, dry mouth, reduced appetite, irritability (4%) and disinhibition (1%)
                                                             EXTERNAL VALIDITY

Generalisability [29]

Applicability [30]

Comments [31]




Depression in adolescents and young adults                                                                                 797
                                                                STUDY DETAILS
Reference [1] (Herman et al 2007)
Herman, K. C., Ostrander, R. et al (2007). 'Empirically derived subtypes of adolescent depression: latent profile analysis of co-occurring
symptoms in the Treatment for Adolescents with Depression Study (TADS)', J Consult Clin Psychol, 75 (5), 716-728.
Affiliation/source of funds [2] Johns Hopkins University School of Medicine, Duke University Medical Center, Duke University Medical School,
authors consultants or advicers to Pfizer, Lilly, Wyeth, GlaxoSmithKline, Jazz, MedAvante, held stock in MedAvante, received research support
from Lilly, received study drug from Lilly and Pfizer, and study funded by the National Institute of Mental Health
Study design [3]                                      Level of evidence [4]        Location/setting [5]
Prospective inception cohort                          II prognostic                Part of TADS study
Patient characteristics [10]                                                                                           Sample size [7]
Mean age = 14.6±1.5 years, 45.6% male, 73.9% White, 12.5% African American, 8.9% Hispanic, 4.8% other                  N= 439
Mean CDRS-R at baseline (T score) = 76±6.43                                                                            Length of follow-up [11]
                                                                                                                       12 weeks of treatment
Selection criteria
Inclusion criteria: Patients with a primary DSM-IV-TR diagnosis of MDD aged 12 – 17 years, ability to receive care as an outpatient, a CDRS-R
score >44, full scale IQ or 80 or higher, no antidepressants being taken at time of consent, depressed mood present in at least 2 of 3 contexts
for at least 6 weeks.
Exclusion criteria : Past or current diagnosis of bipolar disorder, severe conduct disorder, current substance abuse or dependence, pervasive
developmental disorder, thought disorder, concurrent treatment with psychotropic medication or psychotherapy outside the study, two failed
SSRI trials, poor response to clinical treatment containing CBT for depression, intolerance to fluoxetine, confounding medical condition, non-
English speaking patient or parent, and/or pregnancy or refusal to use birth control.
Prognostic factor(s):                                        Data collection method
Class indicators (class of depression)                       Conner’s Parent Rating Scale – Revised (CPRS – R) measuring oppositional,
                                                             inattention, hyperactive, anxious-shy, perfectionism, social problems, and
                                                             psychosomatic
                                                             Derived 5 main types of classes: depressed only (20%), anxious (19%), oppositional
                                                             (32%), severely disruptive (19%) and anxious – severely disruptive (10%)

Potential confounders:
                                                              INTERNAL VALIDITY
Outcome measurement method [12]                                                 Comparison of study groups [14]            Blinding [15]
Global functioning on the Clinical Global Impressions Scale –                   Not provided for different classes         Not stated for
Improvements (1 or 2 for treatment responders, and >2 for treatment non-                                                   predictive factors
responders)
Measurement bias [16]                                                           Follow-up (ITT) [17]
Unlikely                                                                        Used ITT analyses
Overall quality assessment (descriptive) [18] Average quality – no indication of blinding of variables other than      Quality assessment: +
treatment, not clear whether certain subtypes may have dropped out more than others, unclear whether
subgroups similar apart from studies characteristics.
                                                                    RESULTS

Outcome [19] CGI-Improvement
Conclusion: No significant condition x class interactions.

                                                             EXTERNAL VALIDITY

Generalisability: Reasonable generalisability

Comments:




                                                                STUDY DETAILS




798                                                                   Depression in adolescents and young adult
Reference [1] (Karlsson et al 2008)
Karlsson, L., Kiviruusu, O. et al (2008). 'One-year course and predictors of outcome of adolescent depression: a case-control study in Finland', J
Clin Psychiatry, 69 (5), 844-853.
Affiliation/source of funds [2] National Public Health Institute, Turku University Central Hospital, The Social Insurance Institution of Finland,
Kellokowki Hospital, Peijas Hospital, University of Kuopio
Supported by the Hospital District of the University of Helsinki, the Peijas Hopsital, the Yrjoe Jahnsson Foundation, the Finnish Medical
Foundation, the Foundation of Jalmari and Rauha Ahokas and the Finnish Academy
Study design [3]                                        Level of evidence [4]       Location/setting [5]
Prospective inception cohort                            II prognostic               Finland
Patient characteristics [10]                                                                                                      Sample size [7]
81% female, Mean age = 16.4±1.6 years                                                                                             N= 174
28.3% of parents working class, 38.7% of parents lower middle class, 26% of parents upper middle class                            Length of follow-up
81.6% full criteria unipolar MDD, 13.2% dysthymic disorder, 6.9% dysthymic disorder + MDD, 9.2% minor depression                  [11]
79.3% with current psychiatric comorbidity, 74.1% with axis I comorbidity, 57.5% anxiety disorder, 16.7% substance                1 year
use disorder
Selection criteria
Inclusion criteria: Adolescents with current depressive mood disorders (unipolar or bipolar depression on K-SADS-PL)
Exclusion criteria : Aged below 13 or over 19, mentally retarded, insufficient knowledge of the Finnish language, or admission including no
individual appointments
Prognostic factor(s):             Data collection method
Axis I disorders                  K-SADS-PL for DSM-IV
Axis II disorders                 Structured Clinical Interview for DSM-IV axis II personality disorders (SCID-II)
Time of onset                     Time when minimum requirements for each DSM-IV diagnosis were present
episode duration, remission
and recovery
Depressive symptoms               Beck Depression Inventory and HAM-D-17
Psychosocial functioning          Global Assessment of Functioning (GAF)
Potential confounders:
                                                               INTERNAL VALIDITY
Outcome measurement method [12]                                                   Comparison of study groups [14]            Blinding [15]
Persistent MDD                                                                    Not stated                                 Not stated
Recurrent depression (new depressive episode emerging after beginning
of recovery)
Measurement bias [16]                                                             Follow-up (ITT) [17]
Unlikely
Overall quality assessment (descriptive) [18] Good quality – clearly defined outcomes and predictive factors,             Quality assessment: ++
provided sufficient statistical details, low attrition. No blinding.
                                                                      RESULTS

Outcome [19]
Univariate outcome                           Measure of effect/effect size + 95% CI [22]
                                             Persistence (vs            Recurrence (vs             Time to recovery           Time to recurrence
                                             Recovered)                 Recovered)
Sex                                          -                          OR=1.41 [3.56, 5.53]       -                          -
Age                                          -                          -                          HR=0.88 [0.77, 1.00]       -
Episode duration by time 1                   -                          OR=0.99 [0.99, 1.00]       HR=0.97 [0.96, 0.98]       HR=0.99 [0.97, 1.00]
Lifetime age at onset (continuous)           -                          OR=1.30 [1.03, 1.63]       HR=1.27 [1.16, 1.40]       HR=1.31 [1.10, 1.57]
General functioning (GAF) (continuous)       OR=0.96 [0.93, 0.996]      -                          HR=1.04 [1.02, 1.06]       -
Lifetime age at onset <12 years              -                          -                          HR=0.30 [0.16, 0.56]       HR=0.13 [0.02, 0.96]
General functioning (GAF) ≤60                OR=2.85 [1.21, 6.69]       -                          HR=0.36 [0.22, 0.59]       -
First MDD (compared to minor                 -                          -                          HR=0.23 [0.12, 0.45]       -
depression)




Depression in adolescents and young adults                                                                                            799
Recurrent MDD (compared to minor            OR=4.95 [1.13, 21.7]       -                          HR=0.22 [0.11, 0.46]       -
depression)
Dysthymic disorder (compared to minor       -                          -                          HR=0.11 [0.04, 0.31]       -
depression)
Double depression (compared to minor        OR=8.00 [1.24, 51.5]       -                          HR=0.02 [0.01, 0.11]       -
depression)
Any comorbid Axis II diagnosis              -                          OR=3.10 [1.14, 8.37]       -                          HR = 2.38 [1.02, 5.56]
Multiple comorbid Axis I diagnoses          OR=1.96 [1.01, 3.79]       -                          HR=0.49 [0.31, 0.77]       -
Multi variate outcome                       Persistence (vs            Recurrence (vs             Time to recovery           Time to recurrence
                                            Recovered)                 Recovered)
Lifetime age at onset for depression        -                          OR=1.34 [1.02, 1.76]       HR=0.42 [0.20, 0.88]
<12 years
GAF total sum score                         -                                                     HR=0.45 [0.26, 0.76]
First MDD (compared to minor                -                                                     HR=0.13 [0.04, 0.47]
depression)
Recurrent MDD (compared to minor            -                                                     HR=0.09 [0.02, 0.36]
depression)
Double depression (compared to minor        -                                                     HR=0.00 [0.00, 0.38]
depression)
Index episode duration by study entry       -                                                     HR=0.88 [0.81, 0.95]       HR=0.99 [0.97, 1.00]
Any comorbid Axis II diagnosis              -                          OR=3.35 [1.16, 9.65]                                  HR=2.90 [1.19, 7.06]


Conclusion: No independent predictors of persistence were identified. Older age at time of depression onset and having a comorbid Axis II
diagnosis were associated with recurrence.
Longer time to recovery was predicted by older age at presentation, longer episode duration, depressive disorder categories, and lower GAF.
Shorter time to recurrence was associated with have any Axis II comorbidity and a shorter total index episode duration by time 1.
                                                              EXTERNAL VALIDITY

Generalisability: Likely only moderate generalisability, although difficult to tell given the lack of demographic information provided on the
sample.
Comments:




800                                                                    Depression in adolescents and young adult
                                                                 STUDY DETAILS
Reference [1] (Jeong et al 2005) Jeong, Y. J., Hong, S. C. et al (2005). 'Dance movement therapy improves emotional responses and
modulates neurohormones in adolescents with mild depression', Int J Neurosci, 115 (12), 1711-1720.
Affiliation/source of funds [2] Department of Physical Education, Center of Integrative Medicine, Institute of Medical Science, and Department
of Neuropsychiatry, School of Medicine, Wonkwang Univeristy, Iksan, Korea, supported by Wonkwang University,
Study design [3] RCT             Level of evidence [4] Interventional level II     Location/setting [5] School setting, Iksan, Korea
Intervention [6] DMT (n=20) – 45 minute sessions 3 time per week for 12            Comparator(s) [8] Control (n=20) – waitlist, participants were
weeks, designed around themes of awareness of the body, movement                   not involved in any treatment but were invited to participate in a
expression, feelings, images and words, differentiation and integration of         DMT group when the study was completed
feelings
Selection criteria: Students showing high BDI scores were invited to participate if they had a
Inclusion criteria – confirmed diagnosis of depression, parental permission,
Exclusion criteria – past or present diagnosis of psychiatric or internal illness, neuroendocrine disorders, history of regular exercise within the
past 6 months, using prescription medication or any other therapeutic treatment for depression, habitual smoking or drinking
Patient characteristics [10] females only
Intervention group – (n=20) mean age 16 years, height (cm) 161.9±5.6, weight (kg) 57.4±9.3, BMI (kg/m2) 21.9±3.3
Comparator group(s) – (n=20) mean age 16 years, height (cm) 160.5±5.4, weight (kg) 52.8±7.3, BMI (kg/m2) 20.5±2.6
Length of follow-up [11] posttreatment only      Outcome(s) measured [12] Secondary – symptoms of depression using SCL-90-R,
                                                               INTERNAL VALIDITY
Allocation [13]       Comparison of study        Blinding [15]                   Treatment/                     Follow-up (ITT) [17]
randomisation         groups [14]                Person randomising              measurement bias [16]          All participants completed the
assigned by           No significant             groups blind to                 Groups treated and             program, no follow-up past
independent           differences between        experimental procedures         measured the same              posttreatment
person                groups except              none other specified            except for intervention
                      intervention
Overall quality assessment (descriptive) [18] average quality study

                                                                     RESULTS

Outcome [19]               Intervention group [20]             Control group [21]                  Measure of effect/effect size [22]
Depressive symptoms        DMT (n=20)                          Control (n=20)                      Group x time
using SCL-90-R, mean       Pre    51.8±11.8                    Pre 43.6±6.2                        F(1,92) = 68.1 p =0.001
(SD),                      Post 46.4±10.2                      Post 46.1±5.7


                           Clinical importance (1-4) [26] all SCL-90-R subscale scores             Relevance (1-5) [27]
                           decreased significantly in the DMT group
Any other adverse effects [28] none stated

                                                               EXTERNAL VALIDITY

Generalisability [29] generalisable to female population with mild depression

Applicability [30] small sample size however benefits outweigh harms, useful in community settings, low cost treatment

Comments [31] the study also reported reduced levels of stress hormones and increased serotonin blood levels after 12 weeks of DMT
treatment
BDI=Beck Depression Inventory (range 0-39 with higher scores indicating greater number of symptoms of depression); DMT=Dance Movement Therapy;
SCL-90-R=Symptom Check List -90-Revision;




Depression in adolescents and young adults                                                                                           801
                                                                 STUDY DETAILS
Reference [1] (Kennard et al 2008) Kennard, B. D., Emslie, G. J. et al (2008). 'Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric
Responders to Pharmacotherapy for Major Depressive Disorder', Journal of the American Academy of Child and Adolescent Psychiatry, 47 (12),
1395-1404.
Affiliation/source of funds [2] University of Texas Southwestern Medical Center, United States, supported by funding from a NIMH R34
Treatment Development Grant
Study design [3] RCT              Level of evidence [4] Interventional level II       Location/setting [5] Child and adolescent psychiatry
                                                                                      outpatient clinic
Intervention [6] Acute phase – 12 weeks of pharmacotherapy using           Comparator(s) [8] MM+CBT, CBT sessions commenced at week 13,
fluoxetine, starting at 10 mg/day for 1 week increased to 20 mg/day        8-11 x 1 hour sessions over a 6 month period, sessions held weekly
then after 6 weeks of treatment increasing to 30 -40 mg if CGI ≥3          for 4 weeks, biweekly for 2 months and monthly booster sessions for 3
After 12 weeks of treatment non responders were excluded from the          months. First 2 sessions were 1.5 hours long and included a family
study and remaining participants were randomised to MM or MM+RP-           component, 3 family sessions included in CBT protocol
CBT (adequate treatment response measured by CGI-I score of 1 or
2, and depressive symptoms on CDRS-R reduced by 50%)                       Sample size [9] N=22
MM group remained on the dose of fluoxetine to which they had
responded for 24 weeks
Sample size [7] N=24
Selection criteria Adolescents 11-18 years of age, with primary diagnosis of MDD for at least 4 weeks with a CDRS-R score ≥40 and a CGI-S
score of ≥4
Inclusion criteria – normal intelligence, good general medical health,
Exclusion criteria – lifetime history of any psychotic disorder (including psychotic depression), bipolar disorder, anorexia nervosa or bulimia,
history of alcohol or substance abuse within 6 months, concurrent medical condition that would interfere with the study or endanger the
participant, pregnant or breastfeeding females, first degree relative with bipolar I disorder, severe suicidal ideation, previous failure with
fluoxetine or currently taking other psychotropic medication other than stable ADHD treatment


Patient characteristics [10] Mean age 14.3±1.9, 52.2% (n=24) male, 47.8% (n=22) female, 73.9% (n=34) white, 26.1% (n=12) nonwhite, age
of onset of current episode 13.4±2.1
Intervention group – MM group mean age 14.4±2.2, 50% (n=12) male, 50% (n=12) female,66.7% (n=16) white, 33.3% (n=8) nonwhite, age of
onset of current episode 13.3±2.2
Comparator group(s) – MM+CBT mean age 14.3±1.7, 54.5% (n=12) male, 45.5% (n=10) female,81.8% (n=18) white, 18.2% (n=4) nonwhite,
age of onset of current episode 13.5±1.9
Length of follow-up [11] 24 weeks after 12 week acute                  Outcome(s) measured [12] Primary – functioning using CGAS,
treatment phase (36 weeks in total)                                    Secondary – depressive symptoms using CDRS-R, satisfaction with
                                                                       treatment using CSQ-8
                                                              INTERNAL VALIDITY
Allocation [13]                Comparison of study          Blinding [15]                Treatment/                    Follow-up (ITT) [17]
Randomisation method           groups [14]                  Interviewers blind to        measurement bias [16]         ITT - yes
not specified but stratified   No significant differences   treatment allocation         All participants treated
randomisation by level of      between groups on any                                     and measured the same
response and age (11-14,       demographic or clinical                                   except for intervention
and 15+)                       variables
Overall quality assessment (descriptive) [18] good quality

                                                                     RESULTS

Outcome [19]                   Intervention group [20]                   Control group [21]                     Measure of effect/effect size
Depressive symptoms            MM (n=24)                                 MM+CBT (n=22)                          [22]
using CDRS-R mean +            Screening                                 Screening
SD                             59.9±8.3                                  55.9±9.6                               t=1.49 p.14
                               Post acute treatment phase (week12 )      Post acute treatment phase
                               26.7±5.1                                  (week 12) 26.5±5.4                     t=0.11 p.91


Risk of relapse using Cox                                                                                       Greater risk for MM group
proportional hazards                                                                                            Hazard ratio 8.80: 95% CI 1.01,
regression                                                                                                      76.89, x2=3.86, p=.049




802                                                                    Depression in adolescents and young adult
Probability of relapse         MM (n=24)                                   MM+CBT (n=22)
                               Week 16 20    24 36                         Week 16 20 24 36
                                      8% 15% 21% 37%                             4% 5% 8% 15%
Functioning at end of          MM (n=24)                                   MM+CBT (n=22)                               T=-0.42 p=.68
treatment using CGAS           63.5±10.1                                   64.8±9.7
mean + SD

Depressive symptoms at         MM (n=24)                                   MM+CBT (n=22)                               T=1.72 p=.09
end of treatment using         33.6±14.1                                   27.4±8.9
CDRS-R mean + SD


Patient satisfaction with      MM (n=24)                                   MM+CBT (n=22)
treatment using CSQ-8          3.58±0.43                                   3.98±0.05
(Patient)


Discontinuation of             29% (n=7)                                   36% (n=8)                                   X2 1 =.27, p=.60
medication after 24
weeks post acute phase

                               Clinical importance (1-4) [26] length of time to relapse significantly                  Relevance (1-5) [27]
                               lengthened by continuation phase CBT
Any other adverse effects [28] none stated

                                                                EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population

Applicability [30] benefits outweigh harms

Comments [31]

CBT=Cognitive Behavioral Therapy; CDRS-R= Children’s Depression Rating Scale-Revised; CGAS=Children’s Global Adjustment Scale; CGI-S= Clinical
Global Impression Severity; CSQ-8=Client Satisfaction Questionnaire-8; K-SADS-PL=Schedule for Affective Disorders and Schizophrenia for School-Age
Children-Present and Lifetime Version; MDD=Major Depressive Disorder; MM=Medication Management; RP-CBT=Relapse Prevention Cognitive Behavior
Therapy:




Depression in adolescents and young adults                                                                                                803
                                                               STUDY DETAILS
Reference [1] Khumar, S. S., Kaur, P. & Kaur, S. (1993). 'Effectiveness of Shavasana on depression among university students', Indian Journal
of Clinical Psychology 20 (2), 82-87.(Khumar et al 1993)
Affiliation/source of funds [2] Department of Psychology, Punjabi University, Patiala, India, no funding source declared
Study design [3] RCT          Level of evidence [4] Interventional level II          Location/setting [5] Punjabi University, India
Intervention [6] Shavasana yoga, (n=25) 30 minutes per day for 30           Comparator(s) [8] Control group, (n=25) no treatment
days
Selection criteria: unmarried postgraduate female students at Punjabi University, with history of 2-3 months of depression not receiving any
other form of treatment for their depression (drugs, counselling or group lectures), and with no other medical conditions
Inclusion criteria – not specified
Exclusion criteria – not specified
Patient characteristics [10] 20-25 years old, unmarried, postgraduate students at Punjabi University, no medical conditions, no other details
specified,
Intervention group –not specified
Comparator group(s) – not specified
Length of follow-up [11] no follow-up after posttreatment     Outcome(s) measured [12] Secondary – depressive symptoms using Zung
observations                                                  Depression Self Rating Scale
                                                             INTERNAL VALIDITY
Allocation [13]        Comparison of study groups           Blinding [15]         Treatment/ measurement bias           Follow-up (ITT) [17]
Randomisation not      [14]                                 None stated           [16]                                  All participants completed
specified              No significant differences                                 Groups treated and measured the       all assessments, none
                       between groups except for                                  same except for intervention          withdrew from study
                       intervention
Overall quality assessment (descriptive) [18] average quality, insufficient detail in several aspects of analysis

                                                                   RESULTS

Outcome [19]           Intervention group [20]                       Control group [21]                             Measure of effect/effect
                       Shavasana (n=25)                              Control (n=25)                                 size [22]
Depressive                                                                                                          Difference between
symptoms using         Pretreatment 80.89±3.06                       Pretreatment 80.02±2.12                        group
Zung Depression        Midtreatment 69.30±8.18                       Midtreatment 78.70±3.47                        Pretreatment t=1.14
Self Rating Scale,     t=6.51 p 0.01                                                                                              p n.s.
(mean difference in                                                  t=1.59 p n.s.
                                                                                                                    Midtreatment t =5.19
depression scores,
SD)                    Mid treatment 69.30±8.15                      Midtreatment 78.70±3.47 Posttreatment                        p 0.01
                       Posttreatment 57.52±13.49                     77.92±6.04                                     Posttreatment t= 6.75
                       t= 8.29 p 0.01                                t= 1.60 p n.s.                                               p 0.01

                       Pretreatment 80.89±3.06                       Pretreatment 80.02±2.12
                       Posttreatment 57.52±13.49                     Posttreatment 77.92±6.04
                       t=3.66 p 0.01                                 t= 0.55 p n.s.




804                                                                  Depression in adolescents and young adult
Reduction in            Shavasana (n=25)                              Control (n=25)
depressive              Number of severely depressive cases           Number of severely depressive cases
symptoms using          Pretreatment 25 (100%)                        Pretreatment 25 (100%)
Zung Depression
Self-Rating Scale       Midtreatment 15 (60%)                         Midtreatment 25 (100%)
over three              Posttreatment 9 (36%)                         Posttreatment 23 (92%)
assessment points
                        Number of moderately depressive cases         Number of moderately depressive cases
                        Pretreatment 0                                Pretreatment 0
                        Midtreatment 7 (28%)                          Midtreatment 0
                        Posttreatment 1 (4%)                          Posttreatment 2 (8%)

                        Number of mild depressive cases               Number of mild depressive cases
                        Pretreatment 0                                Pretreatment 0
                        Midtreatment 2 (8%)                           Midtreatment 0
                        Posttreatment 4 (16 %)                        Posttreatment 0

                        Number of normal cases                        Number of normal cases
                        Pretreatment 0                                Pretreatment 0
                        Midtreatment 1 (4%)                           Midtreatment 0
                        Posttreatment 11 (44%)                        Posttreatment 0
                       Clinical importance (1-4) [26] benefits outweigh harms                                        Relevance (1-5) [27]

Any other adverse effects [28] none stated

                                                              EXTERNAL VALIDITY

Generalisability [29] some culturally specific aspects to the study however likely to transfer to Australian conditions

Applicability [30] benefits outweigh harms

Comments [31]




Depression in adolescents and young adults                                                                                       805
                                                                      STUDY DETAILS
Reference [1] (Kolko et al 2000) Kolko, D. J., Brent, D. A. et al (2000). 'Cognitive and family therapies for adolescent depression: treatment
specificity, mediation, and moderation', J Consult Clin Psychol 68 (4), 603-614. (see also Brent et al 1997;1998 this study reports follow-up of
the Brent studies to 24 months)
Affiliation/source of funds [2] Western Psychiatric Institute and Clinic, Pittsburgh supported by a National Institute of Mental Health (NIMH)
Grant
Study design [3] RCT                 Level of evidence [4] Level II                      Location/setting [5] Pittsburgh, United States
Intervention [6] Two Phases, Active and Booster                                  Comparator(s) [8] SBFT or NST
Active phase = 12-16 sessions CBT over 12-16 weeks,                              Active phase = 12-16 sessions over 12-16 weeks
Booster phase for completers = 2 - 4 sessions over 2 - 4 months                  Booster phase for completers = 2 - 4 sessions over 2 - 4 months
Sample size [7] CBT (n=37)                                                       Sample size [9] SBFT (n=35) or NST (n=35)
Selection criteria Adolescents13-18 years of age, living with at least one parent or guardian,
Inclusion criteria – meeting criteria for DSM-III-R major depressive disorder, BDI≥13,
Exclusion criteria – psychosis, bipolar I or II, obsessive compulsive disorder, eating disorder, substance abuse in past 6 months, recent
physical or sexual abuse, pregnancy or chronic medical illness
Patient characteristics [10] Mean age 15.6 years ±1.4, 85% Caucasian, 75% female, 57% lived with two parents, mean BDI 24.1±8.1, 32%
had comorbid anxiety, 22% dysthmyic, 16% oppositional, 37% suicidal at intake, median duration of depression 7 months (range 0.5-
87months), mean CGAS score 56.5±8.5,
Intervention group – not specified
Comparator group(s) – not specified
Length of follow-up [11] 24 months                      Outcome(s) measured [12] Primary – functioning, Secondary - depressive symptoms
                                                                INTERNAL VALIDITY
Allocation [13]                          Comparison of study            Blinding [15]         Treatment/             Follow-up (ITT) [17]
Randomisation using Begg and             groups [14]                    Interviewers were     measurement bias       107 recruited, 4 participants
Iglewicz’s modification of Efron’s       There were no significant      blind to treatment    [16]                   never commenced treatment
biased coin toss balancing               differences in diagnoses       status                Participants were      leaving n=103
gender, number of parents in the         or demographics                                      treated the same       78 completed treatment, 62
household and clinically                 between groups                                       except for the         completers received booster
significant suicidality                                                                       interventions          treatment,
Overall quality assessment (descriptive) [18] good quality study
                                                                        RESULTS

Outcome [19]       Intervention group [20]                     Control group [21]                                      Measure of effect/effect
Family                                     CBT                                        SBFT       NST                   size [22]
functioning as     Intake (n=35)        2.7±0.5                Intake (n= 32, 35)     2.6±0.5 2.5±0.5                  Treatment x time on FAD
measured on        Midtreatment (n=35) 2.6±0.6                 Midtreatment (n=29,30) 2.5±0.5 2.5±0.5                  x2(2)=13.89, p<.0001
FAD-GF                                                                                                                 CBT vs NST x2(1)=11.60,
(mean and          Posttreatment (n=30) 2.4±0.5                Posttreatment (n=24,23) 2.5±0.5 2.5±0.4
                                                                                                                       p<.0007
SD)                24 mo f/up (n=34)    2.3±0.5                24 month follow-up      2.3±0.6 2.3±0.5
                                                                                                                       SBFT vs NST x2(1)=7.26,
                                                               (n=26,29)                                               p<.007


Pairwise                                                                                                               CBT had greater impact than
comparisons                                                                                                            SBFT x2(1)=4.81, p<.03 and
on reducing                                                                                                            NST x2(1)=3.79, p<.05
cognitive
distortion
Treatment x                                                                                                            Post treatment
Time using                                                                                                             BDI (p<0.8
BDI and DEP-                                                                                                           DEP-13 (p<.41
13
                                                                                                                       24 months follow-up
                                                                                                                       BDI (p<.62)
                                                                                                                       DEP-13 (p<.92)

                   Clinical importance (1-4) [26] extends initial findings of Brent et al 1997 study                   Relevance (1-5) [27]

Any other adverse effects [28] none stated




806                                                                       Depression in adolescents and young adult
                                                               EXTERNAL VALIDITY

Generalisability [29] likely

Applicability [30] therapists in this study were given 6 months intensive training to conduct the groups to ensure consistency, may affect cost
effectiveness of this treatment
Comments [31] most of the effect results in this aspect of the (Brent 1997) study are not related to primary outcomes for this review

ACQ= Areas of Change Questionnaire; BDI= Beck Depression Inventory (range 0-39 with higher scores indicating greater number of symptoms of
depression); BHS= Beck Hopelessness Scale; CBQ= Conflict Behavior Questionnaire; CBT= Cognitive Behavioral Therapy; CGAS= Children’s Global
Assessment Scale; CNCEQ= Children’s Negative Cognitive Errors Questionnaire; DEP-13=Depression Severity Score developed using 13 items from K-
SADS;FAD-GF= Family Assessment Device-General Functioning; K-SADS-P/E= The Schedule for Affective Disorders and Schizophrenia for School-Age
Children – Present and Lifetime Versions; MDD=Major Depression Disorder; NST= Nondirective Supportive Therapy; SBFT= Systemic-Behavioral Family
Therapy;




Depression in adolescents and young adults                                                                                           807
                                                                  STUDY DETAILS
Reference [1] (Kroll et al 1996) Kroll, L., Harrington, R. et al (1996). 'Pilot study of continuation cognitive-behavioral therapy for major depression
in adolescent psychiatric patients', J Am Acad Child Adolesc Psychiatry, 35 (9), 1156-1161.
Affiliation/source of funds [2] University of Manchester Department of Child and Adolescent Psychiatry, Royal Manchester Children’s
Hospital, UK, Supported by the Medical Research Council of Great Britain
Study design [3] Historical Cohort Study           Level of evidence [4] III-2                   Location/setting [5] Manchester, England
Intervention [6] CBT-A for 5-8 sessions followed by CBT-C for six            Comparator(s) [8] CBT-A for 5-8 sessions
months with sessions every 2-4 weeks                                         Sample size [9] N=12
Sample size [7] N=17
Selection criteria
Inclusion criteria – Adolescants 9-17 years of age with DSM-III-R MDD
Exclusion criteria – severe depressive disorder likely to require nonpsychological treatment, psychotic disorder, taking antidepressants,
inability to complete the questionnaires, autism, severe physical illness or neuroepiliptic disorder
Patient characteristics [10]
Intervention group – N=17 mean age 14.7 years, 7 males, 10 females, mean duration of MDD 50.8 weeks,
Comparator group(s) – N=12 mean age 12.7 years, 5 males, 7 females, mean duration of MDD 44.1 weeks,
Length of follow-up [11] six months                                          Outcome(s) measured [12] Primary – functioning using GAS,
                                                                             Secondary – depressive symptoms using K-SADS and MFQ
                                                                INTERNAL VALIDITY
Allocation [13]                Comparison of study groups [14]          Blinding [15]               Treatment/                  Follow-up (ITT) [17]
Historical control group       The average age of the intervention      Interviewers could not      measurement bias            Treatment group
drawn from a previous          group was significantly greater and      be blinded as the           [16]                        followed up for 6
study conducted at the         they were significantly more             studies took place at       Groups treated the          months with only 1
same clinic                    impaired after remission from the        different times             same except for             participant dropping
                               acute episode than the historical                                    intervention                out
                               controls
Overall quality assessment (descriptive) [18] average quality due to small numbers of participants

                                                                      RESULTS

Outcome [19]                   Intervention group [20]                       Control group [21]                              Measure of effect/effect
Functioning using GAS          CBT-C                                         Historical controls                             size [22]
Mean, SD                       During acute episode 41.7±6.0                 During acute episode       45.6±8.2
                               After remission      66.9±5.20                After remission            78.0±14.9
Depressive symptoms            CBT-C                                         Historical controls
using MFQ                      During acute episode 40.7±9.2                 During acute episode       38.7±11.8
                               After remission      16.1±10.7                After remission            15.1±13.9
Relapse at 3 months            CBT-C                                         Historical control group                        Fisher’s Exact Test
                               1/17 relapse                                  6/12 relapse (50%)                              p<.05


Significantly less relapses                                                                                                  Lee-Desu statistic = 4.4,
in CBT-C group at 6                                                                                                          p<.03
months

                               Clinical importance (1-4) [26] less relapses in the intervention group at all time            Relevance (1-5) [27]
                               points
Any other adverse effects [28] none stated

                                                               EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population however very small sample size

Applicability [30] benefits likely to outweigh harms

Comments [31]

CBT-A= Cognitive Behavioral Therapy – Acute; CBT-C= Cognitive Behavioral Therapy – Continuation; K-SADS= Schedule of Affective Disorders and
Schizophrenia for School-Age Children; MDD= Major Depressive Disorder




808                                                                     Depression in adolescents and young adult
                                                          STUDY DETAILS
Reference [1] Kutcher, S. & Robertson, H. A. (1995). 'Electroconvulsive therapy in treatment-resistant bipolar youth', Journal of
Child and Adolescent Psychopharmacology, 5 (3), 167-175.

Affiliation/source of funds [2] Dalhousie University, Nova Scotia, Canada
Study design [3] Retrospective cohort         Level of evidence [4] Interventional      Location/setting [5] University teaching
                                              level III-2                               hospital with a specialised adolescent
                                                                                        psychiatric unit
Intervention [6] Electroconvulsive therapy (ECT) given              Comparator(s) [8] Usual care
bilaterally using the brief pulse method. One course of
treatment consisted of 6 ECT sessions                               Sample size [9] N=6

Sample size [7] N=16
Selection criteria
Inclusion criteria –
     -    Bipolar disorder using DSM-III-R criteria
     -    Minimal or nonresponse to an adequate 4-6 week trial of combined thymoleptic and neuroleptic treatment.
     -    CBC including differential counts, electrolytes, renal function tests and ECG within normal range
     -    Independent opinion of a psychiatrist not involved in treatment of patients which supports use of ECT
     -    Informed consent signed by both patient and parent

Exclusion criteria –
Patient characteristics [10]
Intervention group – Acute manic state =8/16 (50%), acute depressive state=8/16 (50%), BPRS score at admission=44.1, age at
onset of illness = 15.3 years, number of previous hospitalisations = 3.4, age at current hospitalisation = 19.6

Comparator group(s) – Acute manic state =3/6 (50%), acute depressive state=3/6 (50%), BPRS score at admission=52.1, age at
onset of illness = 15.8 years, number of previous hospitalisations = 4.1, age at current hospitalisation = 18.0

Length of follow-up [11]                                            Outcome(s) measured [12]
Duration of hospitalisation:                                        Secondary: Depressive symptoms – BPRS score, side effects,
Intervention group - mean length of stay = 73.8 days                mean length of stay
Comparator group – mean length of stay = 176 days
INTERNAL VALIDITY
Allocation [13]            Comparison of study         Blinding [15]              Treatment/                 Follow-up (ITT) [17]
Patient preference         groups [14]                 Not relevant –             measurement bias           Yes
                           No apparent                 retrospective chart        [16]                       Intervention group:
                           differences between         review                     Uncertain.                 16/16 (100%)
                           groups                                                 Measurement of             Control group: 6/6
                                                                                  outcomes appears to        (100%)
                                                                                  the same between
                                                                                  groups however, it is
                                                                                  uncertain whether the
                                                                                  groups where treated
                                                                                  similarly apart from the
                                                                                  interventions.
Overall quality assessment (descriptive) [18]
Average quality - Retrospective, chart review diminishes the quality of this cohort study.
RESULTS

Outcome [19]               Intervention group          Control group [21]          Measure of effect/effect size [22]
                           [20]
                                                                                   95% CI [25]

Depressive symptoms        Pre-treatment: 44.1         Pre-treatment: 52.1         Improvement over time:
– BPRS score               Post-treatment: 12.9        Post-treatment: 20.0        Intervention: t=16.19, p<0.0001
                                                                                   Control: t=6.35, p<0.001
                           (S.D. not reported)         (S.D. not reported)
                                                                                   Between groups, post-treatment: t=-2.34, p<0.03
Mean length of stay        73.8 days                   176 days                    No statistical testing




Depression in adolescents and young adults                                                                                      809
                            Clinical importance (1-4) [26]                            Relevance (1-5) [27]

Any other adverse effects [28]
46/166 (28%) ECT treatments were associated with acute side effects:
- Headache (54%)
- Short-term confusion (18%)
- Agitation, hypomanic symptoms , subjective memory loss (9%)
- Vomiting (2%)

EXTERNAL VALIDITY

Generalisabilty [29]
These results are generalisable to a population of young adults who are seriously ill with adolescent onset bipolar disorder and in
whom optimal pharmacologic and psychotherapeutic treatment was refractory.
Applicability [30] Both groups (ECT and usual care) had significant improvements following their respective interventions. The
ECT group showed a statistically significant greater improvement in BPRS scores following treatment, but this treatment was also
associated with some acute side effects. Consideration would have to be given as to whether or not these side effects were
acceptable in a population who were not as seriously ill as the population studied.
Comments [31]
This study is limited in terms of reported outcomes and quality by its retrospective nature.
ECT = electroconvulsive therapy; CBC = complete blood count; BPRS = Brief Psychiatric Rating Scale




810                                                                       Depression in adolescents and young adult
                                                              STUDY DETAILS
Reference [1] (Lewinsohn et al 1990) Lewinsohn, P. M., Clarke, G. N. et al (1990). 'Cognitive-behavioral treatment for depressed adolescents',
Behavior Therapy, 21 (4), 385-401.
Affiliation/source of funds [2] Oregon Research Institute; Oregon Health Sciences University; Oregon Research Institute Eugene Clinic;
supported by a National Institute of Mental Health Research Grant
Study design [3] RCT            Level of evidence [4] Interventional Level II        Location/setting [5] Mental Health Clinic, Oregon, United
                                                                                     States,
Intervention [6] N=21 Adolescent Only; CWD-A course for 14 x 2           Comparator(s) [8] N=19 Waitlist Control, assigned to a group but
hour sessions twice weekly for 7 weeks, or                               waitlisted till the treatment period was completed – 8 weeks,
N=19 Adolescent + Parent; CWD-A course + separate treatment
module for parents for 7 x 2 hour sessions once per week meeting at
same time as adolescents

Selection criteria Adolescents 14-18 years of age
Inclusion criteria – DSM-III diagnosis of major depressive disorder or RDC diagnosis of current episode of minor or intermittent depressive
disorder, currently in grades 9-12 inclusively,
Exclusion criteria – DSM-III or RDC diagnosis of current episode of bipolar disorder with mania, bipolar disorder with hypomania, panic
disorder, generalized anxiety disorder, alcoholism, conduct disorder, or drug-use disorder
Patient characteristics [10]
Intervention group – Adolescent Only – N=21, Mean age 16.15±0.98, 61.9% female, 28.6% living with both parents, 61.9% living with one
parent, 9.5% living with neither parent,
Adolescent + Parent – N=19, Mean age 16.26±1.17, 52.6% females, 36.8% living with both parents, 57.9% living with one parent, 5.3% living
with neither parent,
Comparator group(s) – Waitlist Control – N=19, 57.9% living with both parents, 36.8% living with one parent, 5.3% living with neither parent
Length of follow-up [11] 24 months                    Outcome(s) measured [12] Secondary – depressive symptoms using CES-D, BDI,
                                                      CBCL-D,
                                                            INTERNAL VALIDITY
Allocation [13]        Comparison of study          Blinding [15]     Treatment/ measurement bias         Follow-up (ITT) [17]
Randomisation          groups [14]                  Not stated        [16]                                69 recruited, 10 dropped out before
method not             No significant differences                     Groups appear to be treated         end of treatment, 25% did not
specified              between groups except                          and measured the same except        completed 6 month assessments
                       for intervention                               for intervention                    and 50% did not complete 24 month
                                                                                                          assessments
Overall quality assessment (descriptive) [18] Good quality study
                                                                    RESULTS

Outcome [19]                 Intervention group [20]                  Control group [21]                     Measure of effect/effect size
                             Adol. only                               Waitlist control                       [22]
Depressive symptoms          Pre treatment 13.29±5.21                 Pretreatment 14.89±4.30
using CES-D Mean + SD        Posttreatment 7.19±4.88                  Posttreatment 12.89±4.74

                             Adol + Parent
                             Pretreatment 12.84±6.65
                             Posttreatment 5.68±4.78


Depressive symptoms          Adol. only                               Waitlist control
using BDI Mean + SD          Pretreatment 21.67±11.34                 Pretreatment 23.84±11.43
                             Posttreatment 10.00±11.91                Posttreatment 20.47±10.28

                             Adol. + Parent
                             Pretreatment 21.26±11.35
                             Posttreatment  6.47±8.53




Depression in adolescents and young adults                                                                                    811
Depressive symptoms            Adol. only                                   Waitlist control
using CBCL-D Mean +            Pretreatment      13.67±4.03                 Pretreatment 12.84±5.50
SD                             Posttreatment      8.95±5.42                 Posttreatment 8.31±4.20

                               Adol. + Parent
                               Pretreatment       13.05±4.93
                               Posttreatment       3.52±2.73
Between group measures
for treatment groups,
mean + SD for all
timepoints
                               Adol. Only        Adol. + Parent
CES-D
              1 month          6.76±5.34          5.53±4.03                                                          F(1,38) =4.85, p<.0001
              6 months         6.25±4.54          5.41±3.81
             12 months         6.50±5.72          6.07±3.65
             24 months          7.10±6.79         5.62±3.86
BDI                            Adol. only          Adol. + Parent                                                    F(1, 38)=4.27, p<.0001)
              1 month          9.95±11.18          6.68±7.89
              6 months         8.24±12.53          6.46±11.65
             12 months         6.00±7.06           4.38±4.49
             24 months         8.40±12.48          5.50±6.43
CBCL-D                         Adol. only          Adol. + Parent                                                    F(1,38) =4.08, p<.0001)
              1 month          6.19 ±6.03)          3.32±2.65
             6 months          7.47±6.06            6.54±4.41
             12 months         5.15±3.74            6.23±4.34
             24 months         6.25±7.44            5.88±5.17
Diagnosis of DSM-III           Adol. only                                   Waitlist control                         Decrease in percentage of
Depression using K-            Pretreatment 100%                            Pretreatment 100%                        participants meeting criteria for
SADS-E                         Posttreatment  57.1%                         Posttreatment 94.7%                      depression in the two active
                                                                                                                     groups (Chi square (2, N=59)
                               Adol. + Parent                                                                        =9.41; p<.01)
                               Pretreatment 100%                                                                     Two active treatments combined
                               Posttreatment  52.4%                                                                  vs waitlist control (Fisher’s Exact
                                                                                                                     Test, p<.0003, two tailed)
                                                                                                                     Difference between active
                                                                                                                     treatment groups not significant
                                                                                                                     (Chi square (1, N=40) =0.0001;
                                                                                                                     p>.05)

                               Clinical importance (1-4) [26] significant differences in the Adol.+ Parent           Relevance (1-5) [27]
                               group vs Adol, group were eliminated by the 6 month follow-up
Any other adverse effects [28] nil stated

                                                                  EXTERNAL VALIDITY

Generalisability [29] generalisable to the target population

Applicability [30] benefits outweigh harms

Comments [31]

BDI=Beck Depression Inventory (range 0-39 with higher scores indicating greater number of symptoms of depression); CBCL-D= Child Behavior Checklist-
Depression; CBT=Cognitive Behavioral Therapy; CES-D= Center for Epidemiologic Studies-Depression Scale; CWD-A=Coping with Depression Course for
Adolescents; K-SADS-E= Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiological Version; RDC=Research
Diagnostic Criteria;




812                                                                       Depression in adolescents and young adult
                                                                STUDY DETAILS
Reference [1] Melvin, G. A., Tonge, B. J. et al (2006). 'A comparison of cognitive-behavioral therapy, sertraline, and their combination for
adolescent depression', J Am Acad Child Adolesc Psychiatry, 45 (10), 1151-1161. (Melvin et al 2006)
Affiliation/source of funds [2] Centre for Developmental Psychiatry and Psychology and Faculty of Education, Monash University, Melbourne,
Australia; Developmental and Educational Psychology, Leiden University, The Netherlands; Supported by a grant from Beyond Blue; Australia’s
Depression Initiative; Premier’s Youth Suicide Taskforce, Department of Human Services, Victoria; Australian Rotary Health Research Fund;
and Pfizer Pharmaceuticals,
Study design [3]          Level of evidence [4]        Location/setting [5]
RCT                       Interventional Level II      3 community based clinics (2 suburban 1 regional) in Melbourne, Australia
Intervention [6] CBT alone (n=22) - 12 x 50            Comparator(s) [8] Medication alone (n=26) – sertraline 25 mg/day for 1 week increasing
minute weekly individual sessions and 3 x 50           to 50 mg/day then up to 100 mg /day as determined clinically and depending on
minute monthly booster sessions for adolescents        tolerability, reviewed every 2-3 weeks, (n=26) Or
and companion sessions for parents who wanted          Combination - a combination of both CBT and Medication (n=25) as per protocols for
to participate                                         each individual therapy
Selection criteria;
Inclusion criteria – DSM-IV primary diagnosis of MDD, DD or DDNOS, aged 12-18 years
Exclusion criteria – major physical illness or epilepsy, bipolar disorder, organic brain syndrome, intellectual disability of sufficient severity to
preclude participation in therapy, psychotic disorder, primary diagnosis of substance abuse disorder, active suicidality or other severe psychiatric
disturbance that required acute hospital admission, pregnancy or breastfeeding, or current antidepressant or psychotropic medication treatment,
Patient characteristics [10] Total group N=73, Mean age 15.3years, 25 male / 48 female, 10 parental involvement in program, MDD (n=44),
DD (n=17), DDNOS (n=12)
Intervention group – CBT group (n=22), Mean age 15.0 years, 7 male / 15 female, MDD (n=9), DD (n=4), DDNOS (n=1),
Comparator group(s) – Medication group (n=26), mean age 15.5 years, 7 male / 19 female, MDD (n=10), DD (n=5) DDNOS (n=0),
Combination group (n=25), mean age 15.3 years, 11 male / 14 female, MDD (n=5), DD (n=10), DDNOS (n=0),
Length of follow-up [11] 6 months                 Outcome(s) measured [12] Primary – functioning using FAD-GF, GARFS and GAF;
                                                  Secondary – depressive symptoms using SADS-L, SIQ and RADS,
                                                          INTERNAL VALIDITY
Allocation [13]           Comparison of         Blinding [15]         Treatment/ measurement            Follow-up (ITT) [17]
Randomisation by          study groups          Allocation blinded    bias [16]                         Completed posttreatment, follow-up
independent               [14]                  until after           Groups treated and                CBT (n=22),          21,   19,
statistician using        No significant        pretreatment          measured the same except          Medication (n=26) 21       23,
computer-generated        differences           assessment            for intervention however
assignment to CBT,        between groups        completed             posttreatment and follow-up       Combination (n=25) 20      24
Med or combination        except for                                  assessments not blinded
                          interventions
Overall quality assessment (descriptive) [18] good quality study

                                                                     RESULTS

Outcome [19]           Intervention group       Control group [21]                        Measure of effect/effect size [22]
                       [20]
Proportion of          CBT 86%                  Med 46%              COMB                 Pretreatment - Posttreatment assessments
adolescents with                                                                          CBT vs COMB OR=0.19 CI 0.03, 1.16,
MDD who                                                                                   MED vs COMB, OR=1.31, CI 0.31, 5.48,
responded to each
treatment over time                                                                       MED vs CBT, OR = 6.86, CI 1.12, 41.48
                                                                                          Posttreatment to follow-up assessments,
                                                                                          CBT vs COMB, OR =0.02, CI 0, 3.45,
                                                                                          MED vs COMB, OR = 2.66, CI 0.07, 108.11,
                                                                                          MED vs CBT OR = 84.94, CI 0.83, 8,718.04

Proportion of MDD      Posttreatment            MED                  Posttreatment        OR of full remission
who reached full       CBT                      Not stated           COMB 7%              CBT vs COMB OR=2.7, CI 0.60, 12.14
remission (8 weeks     14%                                           Follow-up            MED vs COMB OR=3.0, CI 0.68, 13-31
asymptomatic)
                                                                     COMB 60%




Depression in adolescents and young adults                                                                                        813
Proportion of                                                                           Posttreatment
participants                                                                            CBT vs COMB, OR=0.71, CI 0.10, 5.12
remitting from DD                                                                       MED vs COMB OR=1.14, CI 0.17, 7.60
or DDNOS over
time                                                                                    MED vs CBT OR=1.6, CI 0.23, 11.27
                                                                                        Odds of depression for DD and DDNOS decreased
                                                                                        significantly between post acute treatment and follow-up
                                                                                        assessment
                                                                                        OR=8.52, CI 2.58, 28.15
Levels of                   CBT                     MED                COMB
depression using        Pretreatment           Pretreatment
RADS (mean and          83.77±13.80             84.92±11.20         83.96±15.01
SD) cutoff score
≥76                     Posttreatment          Posttreatment
                        66.0±15.93             72.92±16.84          71.64±18.28
                        Follow-up              Follow-up
                        60.05±18.10            67.08±20.25          63.32±17.88

Suicidal ideation          CBT                     MED                COMB
using SIQ-J             Pretreatment           Pretreatment
(cutoff score ≥31)      26.05±19.93            29.42±27.24          30.64±24.42
                        Posttreatment          Posttreatment
                        19.41±19.64            24.23±26.90          23.20±20.24
                        Follow-up              Follow-up
                        13.50±9.09             20.96±26.12          19.28±17.72

Functioning using         CBT                     MED                 COMB
FAD-GF                  Pretreatment           Pretreatment
(cutoff score ≥2.17)    2.48±0.45              2.54±0.38             2.45±0.66
                        Posttreatment          Posttreatment
                        2.22±0.52              2.37±0.57             2.28±0.61
                        Follow-up              Follow-up
                        1.99±0.50              2.35±0.51             2.12±0.71

Secondary                                                                                           Pre-F/u      Pre-post       post-F/u
outcome measures                                                                        GAF         1.04*         3.27*           0.15
change in                                                                               GARFS       0.49*         0.79*           0.15
units/month for all                                                                     RADS      -2.12*         -4.62*          -1.12*
participants                                                                            SIQ-J      -1.10*        -2.13*         -0.69*
*significant at p>.05                                                                   FADGF
                                                                                        (adolescent) -0.03*      -0.05*          -0.02
                                                                                        FADGF
                                                                                        (mother) -0.003          -0.02*          -0.06
MDD participants        CBT (71.4%)            MED (33.3%)          COMB (46.6%)
who achieved
partial remission by
post acute
assessment
                        Clinical importance (1-4) [26] all treatment groups             Relevance (1-5) [27]
                        demonstrated statistically significant improvements on
                        outcome measures which were maintained for 6 months
Any other adverse effects [28] adverse effects were reported by 2% of those participants in the medication group, commonly fatigue,
concentration problems and insomnia, 3 participants (6%) discontinued treatment due to adverse events
                                                             EXTERNAL VALIDITY

Generalisability [29] exclusion criteria eliminated an extensive range of severely depressed adolescents that constitute the target population
however ‘the participants were recruited from clinical referrals who have been found to be less responsive to treatment than participants
recruited through advertisement etc (Brent et al 1998)’ (Melvin et al 2006) likely generalisable to community
Applicability [30]
Comments [31] apparently no significant benefit of combined treatment over CBT alone,

CBT=Cognitive Behavioral Therapy; DD=Dysthymic Disorder; DDNOS=Depressive Disorder Not Otherwise Specified; FAD-GF=Family Assessment Device
General Functioning Scale; GAF=Global Assessment of Functioning Scale; GARFS=Global Assessment of Relational Functioning Scale; MDD=Major




814                                                                  Depression in adolescents and young adult
Depressive Disorder; RADS=Reynolds Adolescent Depression Scale; SADS-L=Schedule for Affective Disorders and Schizophrenia for School Age
Children-Lifetime; SIQ-J=Suicide Ideation Questionnaire-Junior;




Depression in adolescents and young adults                                                                                          815
                                                                STUDY DETAILS
Reference [1] (Miklowitz et al 2008) Miklowitz, D. J., Axelson, D. A. et al (2008). 'Family-focused treatment for adolescents with bipolar disorder:
results of a 2-year randomized trial', Arch Gen Psychiatry, 65 (9), 1053-1061.
Affiliation/source of funds [2] Department of Psychology, University of Colorado; Western Psychiatric Institute and Clinic; University of
Pittsburgh School of Medicine; University of Colorado Health Sciences Center, Denver, Supported by NIMH research grants, a Distinguished
Investigator Award from the National Alliance for Research on Schizophrenia and Depression and a Faculty Fellowship from the University of
Colorado Council on Research and Creative Work
Study design [3] RCT                  Level of evidence [4] Interventional level II       Location/setting [5] University and Hospital Clinics,
                                                                                          United States
Intervention [6] FFT-A and protocol pharmacotherapy consisting of          Comparator(s) [8] EC and protocol pharmacotherapy consisting of 3
21 x 50 minute sessions (12 x weekly, 6 x biweekly and 3 x monthly)        x 50 minute weekly family sessions focused on relapse prevention
over 9 months of psychoedcuation, communication enhancement                psychoeducation
training and problem-solving skills training                               Sample size [9] N=28
Sample size [7] N=30
Selection criteria Adolescents 12-17 years 11 months, Mean age 14.5 years (±1.6)
Inclusion criteria - Adolescents with a current DSM-IV diagnosis of bipolar I (n=38), bipolar II (n=6) or NOS (n=6) with history of a at least a
one week episode of manic, mixed or hypomanic symptom or a 2 week episode of depressive symptoms in the previous 3 months. Willingness
to proceed with pharmacotherapy from a study psychiatrist and at least one biological or step-parent willing to participate in family treatment.
Exclusion criteria - no severe psychosis lasting 3 or more months, no evidence of mental retardation, neurological illness or pervasive
developmental disorder, no substance or alcohol disorders in the prior 3 months, no eating disorder or medical disorder requiring immediate
hospitalization,


Patient characteristics [10] N=58, mean age 14.5 years±1.6, 56.9% female (n=33), 43.1% male (n=25), bipolar I 65.5% (n=38), bipolar II
10.3% (n=6), NOS 24.1% (n=14)
Intervention group – not stated
Comparator group(s) – not stated
Length of follow-up [11] 2 years                                     Outcome(s) measured [12] Primary –functioning using the CGAS,
                                                                     Secondary – resolution or remittance of depressive symptoms using
                                                                     PSR, DRS and K-SADS-PL and Mania using MRS
                                                         INTERNAL VALIDITY
Allocation [13]               Comparison of study           Blinding [15]                 Treatment/                     Follow-up (ITT) [17]
Randomisation using           groups [14]                   Independent assessors         measurement bias [16]          All randomised
Efron biased coin             No significant differences    blind to participant          Groups treated and             participants included in at
procedure                     between demographic           allocation.                   measured the same              risk sample, 82.8%
Randomizations stratified     and clinical variables of                                   except for intervention        completed year 1
by study site.                groups or across sites                                                                     treatment and
                                                                                                                         assessments and 62.1%
                                                                                                                         completed year 2
                                                                                                                         treatment and
                                                                                                                         assessments
Overall quality assessment (descriptive) [18] Average quality study


                                                                    RESULTS

Outcome [19]                  Intervention group [20]       Control group [21]             Measure of effect/effect size [22]
                                                                                           91.4% (n=53) experienced full recovery during 2 years
Time to recovery (from                                                                     of study, mean time 19.8±3.28 weeks,
randomisation till PSR                                                                     No difference between groups (x2 1 =0.95; p=.33;
score ≤2 for ≥4 weeks for                                                                  hazard ratio [HR], 1.33, mean [SD] FFT-A duration
depressive symptoms)                                                                       17.4 [±3.74] weeks, mean [SE] EC duration, 22.3
                                                                                           [±5.40] weeks)


Rate of recovery from         FFT-A                         EC                             FFT-A more rapid recovery (x2 1 =4.36; p=.04; HR, 1.85;
index episode depression      100% 30/30                    89.3% 25/28                    95% CI 1.04, 3.29)
symptoms                      Mean time to recovery         Mean time to recovery          No effect of site P=.81 and no interaction between
                              10.2±2.1 weeks, (25th         14.1±3.34 weeks, (25th         treatment and site P=.55
                              percentile of median, 2       percentile of median, 4
                              weeks 95% CI 1, 4)            weeks; 95% CI, 3, 4)




816                                                                   Depression in adolescents and young adult
Time to recovery for          15.3±4.47 weeks               22.5±8.01 weeks                (HR, 4.87; 95% CI, 1.67, 14.18)
subsample of 18 patients
with a major depressive
episode prior to
randomisation

Time spent in acute state     3.3 weeks; 95% CI, 2.7,       5.0 weeks, 95% CI, 4.2,        x2 1 =13.03; P<.0001
of depression over 2          4.0)                          5.9;
years
Time spent without            70.3% of total weeks          66.3% of total weeks           X2 1 =5.93; P=.02
symptoms of depression        (estimate 52.6 weeks,         (estimate, 48.3 weeks;
over 2 years                  95% CI, 50.0, 55.4)           95% CI, 45.7, 51.0)


Reduction in mood                                                                          FFT-A vs EC (F 1,5017 =7.49, P=.006)
severity scores over 2
years

Trajectory of mood                                                                         Treatment x time x interaction, linear effect
symptom PSR                                                                                F 1,5014 =4.70, P=.03; difference in -2 log-
depression scores                                                                          likelihood 2 =14.0, P<.0001)
PSR depression scores                                                                      Psychosocial group x time interaction (linear trend,
for 2 years                                                                                F 1,5014 =9.08, P=.003; quadratic trend, F 1,5014 =4.62,
                                                                                           P=.03; difference in -2-log-likelihood ratio test for
                                                                                           treatment effects, 13.8; P<.01)

Rate of recovery from         1 year follow-up 96.7%        1 year follow-up 100%          Group differences in time to recover
mania or hypomania            (29/30)                       (28/28)                        FFT-A (mean [SE], 7.6 [1.37] weeks)
                              2 year follow-up              2 year follow-up
                                                                                           EC (mean 13.79 [3.54] weeks
                                                                                           (x2 1 =2.53; P=1.1 HR, 1.58; 95% CI, 0.9, 2.8)
                              Clinical importance (1-4) [26] shorter recovery time         Relevance (1-5) [27]
                              and less time and less severe depressive symptoms
                              with FFT-A
Any other adverse effects [28] none stated

                                                              EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population

Applicability [30] benefits outweigh harms

Comments [31] unable to specify which aspect of FFT-A produced the benefit – more contact hours, access to therapists or content of sessions

CGAS=Children’s Global Assessment Scale; DRS=Depression Rating Scale; EC=Enhanced Care; FFT-A=Family-Focused Treatment for Adolescents; K-
SADS-PL=Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Episode version; MDD=Major Depressive
Disorder; MRS=Mania Rating Scale; NOS=Not Otherwise Specified; PSR= Adolescent Longitudinal Interval Follow-up Evaluation Psychiatric Rating
Scales;




Depression in adolescents and young adults                                                                                           817
                                                               STUDY DETAILS
Reference [1] Mufson, L., Weissman, M. M. et al (1999). 'Efficacy of interpersonal psychotherapy for depressed adolescents', Arch Gen
Psychiatry 56 (6), 573-579. (Mufson et al 1999)
Affiliation/source of funds [2] Division of Clinical-Genetic Epidemiology and Department of Child Psychiatry, New York State psychiatric
Institute and College of Physicians and Surgeons, Columbia University, New York, Supported by a NIMH First Award and by Center to Study
Youth Depression, anxiety and Suicide Grant from the National Institute of Mental Health, Bethesda
Study design [3]              Level of evidence [4]             Location/setting [5] Child Anxiety and Depression Clinic at Babies Hospital
RCT                           Interventional Level II           Columbia Presbyterian Medical Center, New York and Clinical Research
                                                                Center, New York State Psychiatric Institute, New York
Intervention [6] weekly IPT sessions for 12 weeks with a        Comparator(s) [8] Clinical monitoring with a therapist for 30 minute session
once weekly additional phone contact with the therapist         monthly with the option for a second session within the month, to discuss
during the first 4 weeks                                        depressive symptoms but not give advice or skills training only listen
Sample size [7]                                                 supportively
(n=24)                                                          Sample size [9] (n=24)
Selection criteria
Inclusion criteria – Adolescents, English speaking with normal intelligence, aged between 12-18 years, with a legal guardian who could give
informed consent, and who met the criteria for a DSM-III-R major depressive disorder and a HAM-D score of ≥15
Exclusion criteria – Patients who were actively suicidal, were in another treatment for the same condition, had a chronic medical illness, or met
criteria for psychosis, bipolar 1 or 11, conduct disorder, substance abuse disorder, current eating disorder, and/or obsessive-compulsive
disorder
Patient characteristics [10] no significant difference between groups on sex, mean age, ethnicity, socioeconomic status, history of suicide
ideation or baseline diagnoses
Intervention group – N=24; Mean age 15.7±1.4, 75% female, 79.2% Hispanic, 66.7% living in single parent home, comorbid diagnoses – 29%
dysthymic disorder, 88% any anxiety disorder, 30% history of suicide attempt,
Comparator group(s) – N=24 Mean age 15.9±1.7, 70.8% female, 62.5% Hispanic, 70.8% living in single parent home, comorbid diagnoses –
dysthymic disorder 13%, any anxiety disorder 88%, history of suicide attempt 25%.
Length of follow-up [11] 12 weeks of              Outcome(s) measured [12] Primary - global and social functioning and problem-solving skills
treatment then no further observations            using CGAS and SAS-SR, Secondary - diagnoses using DISC 2.3, depressive symptoms
                                                  using HAM-D, BDI, and K-SAD-E
                                                             INTERNAL VALIDITY
Allocation [13]                    Comparison of study        Blinding [15]           Treatment/                   Follow-up (ITT) [17]
Randomization schedule using       groups [14]                All independent         measurement bias [16]        Completion in IPT group
the Statistical Analysis System    No significant             therapists or           unlikely given the           88%, in control group 46%,
to draw numbers, the lowest        differences between        evaluators were         similarity between           (due to suicidality, psychotic
numbers in each 1-10 block         demographics or            blind to the            groups, measurements         features and non-compliance)
were assigned IPT and the          baseline                   treatment group of      the same only the
highest 5 numbers assigned to      measurements of each       the patient             intervention differed
control                            group
Overall quality assessment (descriptive) [18] Good quality study although high attrition rate
                                                                   RESULTS

Outcome [19]                  Intervention group              Control group                Measure of                 Benefits (NNT) [23]
Intention to treat (n=48)                                                                  effect/effect size         At week 12 an ANCOVA
Depressive symptoms           IPT-A n=24                      n=24                          F      df       P         showed IPT patients were
using HAM-D:                  Week 0 19.2±7.5                 Week 0 18.7±8.6              ....   ....     ....       significantly less
                                                                                           6.0 1,45 .02               depressed (mean =2.4,
                              Week 12 6.3±7.7                 Week 12 11.8±8.9                                        ±1.6) than control (mean
Intention to treat (n=48)     Week 0 18.8±8.5                 Week 0 22.8±10.6             F        df       P        4.2 ±1.1) (F 1,37 =18.8.
Depressive symptoms           Week 12 5.9±8.1                 Week 12 12.9±12.6            ....    .....    ....      P<.0001)
using BDI:                                                                                 4.2    1,44     .05        Significantly more IPT
                                                                                                                      patients reported as
Completers n=32               n=21                            n=11                         F      df    P             improved than controls
Depressive symptoms           Week 0 18.6±7.6                 Week 0 15.9±8.0              .... .... . ...            (x2 1 =16.7, P<.0001,
using HAM-D                    Week 12 4.9±5.7                Week 12 11.5±9.4             7.2 1,28 .01               Fisher exact test, 2 tailed
Completers n=32               n=21                            n=11                         F       df    P
Depressive symptoms           Week 0 17.9±8.2                 Week 0 17.2±11.4             ....    .... ....
using BDI                     Week 12 4.4±5.9                 Week 12 9.4±12.4             2.4    1,29 .14




818                                                                  Depression in adolescents and young adult
Social functioning using        School 2.2±1.3                   School 1.9±0.97                F 1.7    df 1,40   P.20
SAS-SR, Intention to treat      Friends 1.9±0.87                 Friends 2.4±0.96               F5.8    df 1,44    P.02
(n=48) Week 12                  Family 1.8±0.83                  Family 1.9±0.86                F1.4    df 1,44    P.24
                                Dating 2.5±1.0                   Dating 3.6±1.2                 F5.9    df 1,43    P.02
                                Total overall functioning        Total overall functioning
                                         1.9±0.63                          2.2±0.70             F 7.1 df 1,44 P.01


                                Clinical importance (1-4) [26]                                  Relevance (1-5) [27]
                                Significant benefits for reducing symptoms of                   Evidence of effect in relevant outcomes
                                depression
Any other adverse effects [28] none stated

                                                                EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population although exclusion criteria quite extensive and rigorous training for clinicians

Applicability [30] benefits outweigh harms although no long term follow up

Comments [31]

BDI= Beck Depression Inventory (range 0-39 with higher scores indicating greater number of symptoms of depression); CGAS= Children’s Global
Assessment Scale; DISC 2.3=Diagnostic Interview Schedule for Children Version 2.3; HAM-D= Hamilton Rating Scale for Depression; IPT-A= Interpersonal
Psychotherapy for Depressed Adolescents; K-SADS-E= Schedule for Affective Disorders and Schizophrenia for School-Aged Children; SAS-SR= Social
Adjustments Scale-Self Report Version (range 1-5 with higher scores indicating worse functioning);




Depression in adolescents and young adults                                                                                              819
                                                                 STUDY DETAILS
Reference [1] (Mufson et al 2004) (Young et al 2006b) Mufson, L., Dorta, K. P. et al (2004). 'A randomized effectiveness trial of interpersonal
psychotherapy for depressed adolescents', Arch Gen Psychiatry 61 (6), 577-584.
Young, J. F., Mufson, L. & Davies, M. (2006). 'Impact of comorbid anxiety in an effectiveness study of interpersonal psychotherapy for
depressed adolescents', J Am Acad Child Adolesc Psychiatry, 45 (8), 904-912.

Affiliation/source of funds [2] Department of Clinical and Genetic Epidemiology, New York State Psychiatric Institute and Department of
Psychiatry, Columbia University, New York, Funded by a grant from the Substance Abuse and Mental Health Administration and a grant from
the Psychotherapy Core of the National Institute of Mental Health Child Psychiatry Intervention Research Center, Rockville,
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, funded by the Substance Abuse and Mental
Health Administration grant and the Psychotherapy Core of the NIMH Child Psychiatry Intervention Research Center grant
Study design [3]              Level of evidence [4]                         Location/setting [5] Five school-based mental health clinics in New
RCT                           Interventional level II                       York City, New York
Intervention [6] IPT from school-based health clinic clinicians, 12         Comparator(s) [8] TAU whatever treatment the participant would
sessions over 12-16 weeks, mean number of sessions attended 10.5            have received if the study had not been in place, mean number of
Sample size [7] n=34                                                        sessions attended 7.9 Sample size [9] n=29
Selection criteria adolescents 12-18 years of age, referred to mental health clinicians in 5 school-based health clinics
Inclusion criteria – HAM-D of ≥10 and a CGAS score of ≤ 65, DSM-IV diagnosis of major depression or depressive disorder not otherwise
specified, must have parental consent to participate
Exclusion criteria – not eligible if actively suicidal, mentally retarded, had a life-threatening medical illness or current diagnosis of substance
abuse disorder, psychosis or schizophrenia, were currently in treatment for depression or taking antidepressant medication
Patient characteristics [10] 15.9±1.9 years , 84% female, 71% Latino, 68% (n=43) positive for at least one anxiety disorder, 32% positive for
social phobia, 38% positive for panic, and 41% positive for GAD,
Intervention group – n=34, mean age 15.3±2.1 years, 91.2% (n=31) female, 76.5% (n=26) Hispanic, 79.3% (n=23) living in single parent home
(some participants not living with parents hence higher percentage), current suicide ideation 39.4% (n=13), history of suicide attempt 14.71%
)n=5), diagnoses = major depression 52.9% (n=18), dysthymic disorder 14.7% (n=5), double depression 5.9% (n=2), depressive disorder NOS
11.8% (n=4), and adjustment disorder 14.8% (n=5),
Comparator group(s) – n=29, mean age 14.9±1.7 years, 75.9% (n=22) female, 65.5% (n=19) Hispanic, 75% (n=21) living in single parent
home, current suicide ideation 27.59% (n=8), history of suicide attempt 7.14% (n=2), diagnoses = major depression 48.3% (n=14), dysthymic
disorder 20.7% (n=6), double depression 6.9% (n=2), depressive disorder NOS 10.3% (n=3), Adjustment disorder 13.8% (n=4).
Length of follow-up [11] 12 weeks of treatment then a phone            Outcome(s) measured [12] Primary: Global and Social functioning using
call at 16 weeks for assessment using HAM-D and CGAS                   CGAS, and SAS-SR, Secondary - Recovery and/or reduction in depressive
                                                                       symptoms using HAM-D, BDI,
                                                               INTERNAL VALIDITY
Allocation [13]                 Comparison of           Blinding [15]            Treatment/               Follow-up (ITT) [17]
Randomisation occurred at       study groups [14]       Assessors and            measurement bias         7 failed to complete the treatment, 4 from
clinician and student level     The treatment           independent              [16]                     the IPT group (2 discontinued treatment,
with the use of a table of      groups did not differ   evaluators who           Unlikely due to          1 changed schools and the other couldn’t
random numbers. Mental          significantly on        conducted the            similarities between     maintain contact with their guardian, and
health clinicians were          demographics or         assessment               groups and all           2 were withdrawn due to non compliance)
randomised to provide IPT       baseline                interviews were          participants were        and 3 withdrew from the TAU group (1
or TAU. Adolescents were        measurements            blind to the             measured and             needed medication and 2 changed
randomised to either IPT                                participant’s            treated the same         schools).
or TAU within schools                                   treatment groups         except for the
                                                                                 intervention
Overall quality assessment (descriptive) [18] good quality study
                                                                     RESULTS

Outcome [19]                      Intervention group [20]              Control group [21]                      Measure of effect/effect size [22]



Intent to treat sample            N=34                                 N=29                                    F 4.62, df2,60 P.04, ES 0.50
Depression symptoms using         Baseline 18.9±5.9                    Baseline 18.3±5.0
HAM-D, mean (SD)                  Week 12 8.7±8.0                      Week 12 12.8±8.4




820                                                                     Depression in adolescents and young adult
Adolescents with probable       IPT-A (n=22)              TAU (n=21)                Total participants (n=43),
anxiety disorder HAM-D,         Baseline 20.4±5.3         Baseline    19.5±5.0      Baseline 19.9±5.1
mean (SD)                       Posttreatment 9.5±8.7     Posttreatment 15.8±8.1    Posttreatment 12.6±8.9
                                                                                    t(41) = 2.42, p<.05
Adolescents without             IPT-A (n=12)              TAU (n=8)                 Total participants (n=20),
comorbid anxiety, HAM-D         Baseline 16.2±6.3         Baseline 15.3±3.9         Baseline 15.8±5.4
mean (SD)                       Posttreatment 7.1±6.5     Posttreatment 5.5±4.3     Posttreatment 7.1±6.5
                                                                                    t(61)=-2.96, p<.01
                                                                                    Comorbidity and treatment condition
                                                                                    F 1,58 =3.44, p=.07
Social functioning using        IPT-A group (n=34)        TAU group (n=29)          F 5.03 df2,60 P.04 ES 0.54
CGAS, mean (SD)                 Baseline 52.6±5.3         Baseline 52.7±6.3
                                Week 12 66.7±13.0         Week 12 59.5±13.5
Adolescents with comorbid       IPT-A group (n=22)        TAU group (n=21)
anxiety, CGAS mean (SD)         Baseline 52.2±5.1         Baseline 52.1±6.2
                                Posttreatment 67.4±14.3   Posttreatment 56.9±14.4
Adolescents without             IPT-A group (n=12)        TAU group (n=8)
comorbid anxiety, CGAS          Baseline 53.2±5.7         Baseline 54.4±6.8
mean (SD)                       Posttreatment 65.4±10.5   Posttreament 66.4±7.6
Global functioning using CGI    N=34                      N=29
(IE)                            Baseline 3.9±0.8          Baseline 3.8±0.7          F 4.89 df2,60 P.03 ES 0.48
Severity of illness             Week 12 2.4±1.3           Week 12 3.0±1.4
Global functioning using CGI    N=34                      N=29
(IE)                            Baseline 5.0±0            Baseline 5.0±0            F 5.28 df1,61 P .03 ES 0.59
Improvement                     Week 12 2.3±1.3           Week 12 3.1±1.6


Depressive symptoms using       N=34                      N=29
BDI                             Baseline 20.8±8.7         Baseline 21.8±8.5         F 2.21 df2,60 P .14 ES 0.37
                                Week 12 8.4±11.0          Week 12 12.3±9.7
Social functioning using        N=34 School               N=29 School
SAS-SR                          Baseline 2.40±0.60        Baseline 2.34±0.80
                                Week 12 2.07±0.84         Week 12 2.33±1.21         F 1.48 df2,60 P .23 ES 0.26
                                Friends                   Friends
                                Baseline 2.78±0.62        Baseline 2.80±0.61
                                Week 12 2.21±0.73         Week 12 2.46±0.82         F 1.70 df2,60 P .20 ES 0.33
                                Family                    Family
                                Baseline 2.65±0.83        Baseline 2.48±0.74
                                Week 12 1.86±0.79         Week 12 2.10±0.72         F 2.81 df2,60 P .10 ES 0.32
                                Dating                    Dating
                                Baseline 3.66±1.06        Baseline 3.47±1.25
                                Week 12 2.87±1.25         Week 12 3.40±1.22         F 4.68 df2,60 P .03 ES 0.43
                                Overall                   Overall
                                Baseline 2.87±0.49        Baseline 2.77±0.52
                                Week 12 2.23±0.66         Week 12 2.59±0.67         F 7.04 df2,60 P .01 ES 0.55
Significant correlation                                                             CGI (r=0.33; P=.008)
between age and severity of
illness on CGI between 12-
14 vs 15-18 years and age
and global functioning on the
CGAS                                                                                CGAS (r=0.36; P=.004)




Depression in adolescents and young adults                                                               821
Adolescents with probable          IPT-A group (n=13)                      TAU group (n=13)                         OR =3.98, 95% CI 0.89, 17.79,
GAD (n=13) were 4 times            84.6% (n=11) improvement rate           53.8% (n=7) improvement rate             p=.07
more likely to show                                                                                                 Recovery rates in two groups
improvement in their anxiety                                                                                        differed significantly X2 1 =4.07, p<.05
if they received IPT-A as
compared to TAU

                                   Clinical importance (1-4) [26]                                                   Relevance (1-5) [27]
                                   Significant benefit in the older adolescent age group (15-18) with more          Demonstrates effectiveness of
                                   severe symptoms, Reduced symptoms of depression and higher                       treatment in school based clinics
                                   functioning in IPT group especially for adolescents with comorbid
                                   anxiety
Any other adverse effects [28] none stated

                                                                  EXTERNAL VALIDITY

Generalisability [29] likely generalisable to the target population as effective when provided in ‘real world’ setting by community clinicians
however majority of population in this study were Hispanic females
Applicability [30] benefits appear to outweigh the harms

Comments [31] proven effectiveness of treatment in community school setting rather than mental health clinic or university controlled
environment
BDI= Beck Depression Inventory (range 0-39 with higher scores indicating greater number of symptoms of depression); CGAS= Children’s Global
Assessment Scale; CGI (IE)= Clinical Global Impression Scale (Independent Evaluator); DISC 2.3=Diagnostic Interview Schedule for Children Version 2.3;
GAD=Generalized Anxiety Disorder; HAM-D= Hamilton Rating Scale for Depression; IPT-A= Interpersonal Psychotherapy for Depressed Adolescents; K-
SADS-E= Schedule for Affective Disorders and Schizophrenia for School-Aged Children; NOS= Not Otherwise Specified; SAS-SR= Social Adjustments
Scale-Self Report Version (range 1-5 with higher scores indicating worse functioning); TAU= Treatment As Usual;




822                                                                        Depression in adolescents and young adult
                                                              STUDY DETAILS
Reference [1] (Rohde et al 2001)Rohde, P., Clarke, G. N. et al (2001). 'Impact of comorbidity on a cognitive-behavioral group treatment for
adolescent depression', J Am Acad Child Adolesc Psychiatry, 40 (7), 795-802.
Affiliation/source of funds [2] Oregon Research Center, Center for Health Research, Kaiser Permanente Research Institute
Supported in part by NIHM grants
Study design [3]                                    Level of evidence [4]       Location/setting [5]
Prospective inception cohort (for the purposes of   II prognostic               Recruited from 2 sites (Eugene and Portland, Oregon) by
prognosis)                                                                      announcements to health and school professionals, media and
                                                                                advertisements
Patient characteristics [10]                                                                                            Sample size [7]
Adolescents aged 14 – 18, mean age = 16.2±1.2 years, 67.5% female, 43.7% from two-parent families, 34.4% had            N= 151
one or more parents with a bachelors-level education or higher, 96.0% White
                                                                                                                        Length of follow-up
58.9% had MDD, 23.8% had dysthymia or intermittent depression (but not MDD), 17.2% had MDD superimposed on a            [11]
more chronic depression (double depression)
                                                                                                                        24 months
39.7% had one or more lifetime comorbid diagnosis at intake, 21.2% anxiety disorders (specific phobia – 7.9%, social
phobia – 6.6%, overanxious disorder – 6.0%), 19.9% attention-deficit disorder and disruptive behaviour disorders,
11.3% substance use disorders (8.6% hard drug use, 5.3% alcohol use disorder)
48/60 with lifetime comorbidity had diagnosis in only one category, 9 had diagnoses in 2 categories, 5 had diagnoses
in 3 categories
Selection criteria
Inclusion criteria: adolescents meeting DSM-III or DSM-III-R criteria for major depression disorder (MDD) or dysthymia
Exclusion criteria : 1) exhibited current mania/hypomania, panic disorder, generalised anxiety disorder, conduct disorder, psychoactive
substance abuse/dependence, 2) lifetime organic brain syndrome, mental retardation, or schizophrenia, 3) were currently receiving other
treatment for depression and were unwilling to discontinue, or 4) needed immediate acute treatment
Prognostic factor(s):                                     Data collection method
Presence of a lifetime comorbidity                        Interviewed with the Schedule for Affective Disorders and Schizophrenia for School-
                                                          Aged Children – Epidemiological Version (K-SADS), and the Longitudinal Interval
                                                          Follow-up Evaluation (LIFE)
Treatment condition                                       16 sessions CBT group for adolescent only (A)
                                                          16 sessions CBT group for adolescents with 9 sessions for parents (A + P)
                                                          or waitlist control (WL)
Potential confounders: -
                                                            INTERNAL VALIDITY
Outcome measurement method [12]                                              Comparison of study groups [14]           Blinding [15]
Level of functioning on the Global Assessment of Functioning (GAF) scale     Lifetime comorbidity was unrelated to     Not stated
Depressive symptoms on the BDI                                               treatment condition assignment and
Recovery on K-SADS and LIFE                                                  demographic variables
Recurrence on K-SADS and LIFE
Attendance of group sessions and homework
Measurement bias [16]                                                        Follow-up (ITT) [17]
Likely controlled for                                                        Completer data only. High attrition at 12 and 24 months
Overall quality assessment (descriptive) [18] Average quality study – high dropout and completer analyses       Quality assessment: +
only, unclear on characteristics of those who dropped out and those followed up, and outcomes not clearly
defined,
                                                                  RESULTS

Outcome [19]                            Lifetime               No lifetime             Measure of effect/effect size + 95% CI [22]
                                        comorbidity            comorbidity
Mean change in depressive               13.7±10.9              10.4±10.2               All subjects:
symptoms on BDI (pre – post)                                                           F(1,44)=3.97, p=0.048, Cohen’s d=0.30
                                                                                       As a function of treatment condition:
                                                                                       F(2,142) = 0.13, p=0.89




Depression in adolescents and young adults                                                                                    823
Recovered at posttreatment               51.7%                    50.5%                   Wald(1)=0.002, p=0.96,
                                                                                          OR=0.98 [0.49, 1.96]
                                                                                          As a function of treatment condition:
                                                                                          Wald(2)=2.06, p=0.36
Recovered during followup                83.3%                    93.2%                   χ2=(N=95) =2.32, p=0.13, OR=2.75 [0.72, 10.51]
Participation at various follow-ups      Post: 83.3%              Post: 80.5%             χ2=(N=185)=0.23, p=0.63, OR=1.21 [0.56, 2.62]
                                         12 months: 62.5%         12 months: 54.0%        χ2=(N=185)=1.42, p=0.26, OR=1.42 [0.78, 2.60]
                                         24 months: 52.6%         24 months: 53.1%        χ2=(N=185)=0.01, p=0.97, OR=0.99 [0.55, 1.78]
Depression recurrence                    25.0%                    12.5%                   χ2=(N=65)=1.65, p=0.20, OR=2.33 [0.63, 8.70]
Global functioning                       Pre: 54.4±7.4            Pre: 60.0±7.4           t(97)=3.66, p<0.01, Cohen’s d=0.76
                                         Post: 67.7±12/8          Post: 69.6±13.3         t(93)=0.72, p=0.48, Cohen’s d=0.14
                                         12 months:               12 months:              t(68)=0.70, p=0.48, Cohen’s d=0.16
                                         75.5±9.5                 77.2±10.9
                                         24 months:               24 months:              t(66)=2.56, p=0.01, Cohen’s d=0.55
                                         74.7±11.4                80.9±8.6
Conclusion: No significant effects for treatment condition x lifetime comorbidity on depressive symptoms or recovery rate.
Having a lifetime comorbidity influenced functioning levels prior to treatment, and functioning at 24 months, but did not affect depression levels
or participation in follow-up.
                                                              EXTERNAL VALIDITY

Generalisability: Unclear how generalisable would be given the method of recruitment (referrals from a range of sources and advertisements),
and the exclusion criteria (excluding those currently treated or not wanting to change). From the United States, with moderate applicability.
Comments:




824                                                                    Depression in adolescents and young adult
                                                                STUDY DETAILS
Reference [1] (Rohde et al 2004) Rohde, P., Clarke, G. N. et al (2004). 'An efficacy/effectiveness study of cognitive-behavioral treatment for
adolescents with comorbid major depression and conduct disorder', J Am Acad Child Adolesc Psychiatry, 43 (6), 660-668.
Affiliation/source of funds [2] Oregon Research Institute, Eugene Oregon, Center for Health Studies, Kaiser Permanente, Portland Oregon,
California Youth Authority Stockton, funded by a grant from the NIMH, Bethesda,
Study design [3]       Level of evidence [4]         Location/setting [5] Department of Youth Services, Juvenile Justice Department, Lane
RCT                    Interventional level II       County, Oregon
Intervention [6] CWD-A (n=45) – a group cognitive-behavioral        Comparator(s) [8] LS (n=48) – 16 x 2 hour sessions over 8 weeks with 6-
intervention for depressed adolescents with comorbid conduct        12 (mean 9.8) adolescents teaching basic life skills such as filling job
disorder, run as 16 x 2 hour sessions over 8 weeks, with groups     applications, how to rent an apartment as well as academic tutoring
of ≈10 individuals (7-16 mean 10.4), includes mood monitoring,      As well as usual care e.g. pharmacotherapy, residential treatment for drug
conflict resolution and relapse prevention,                         and alcohol or incarceration and non-research outpatient mental health
As well as usual care e.g. pharmacotherapy, residential             treatment
treatment for drug and alcohol or incarceration and non-research
outpatient mental health treatment
Selection criteria:
Inclusion criteria – 13-17 years of age, current MDD, current CD, Expected residence in Lane County for the next 12 months and speak
English
Exclusion criteria – charges of first-degree assault, robbery, homicide or rape, and psychotic symptoms
Patient characteristics [10] (N=93) Mean age 15.1±1.4, 48.4% (n=45) female, 80.6% (n=75) white, 15.1% (n=14) residing with both biological
parents, duration of current MDD 81.3 weeks (±119.5), duration of current CD 185.3±115.5 weeks, Number of current diagnoses 4.5±1.7,
number past suicide attempt 39.8% (n=37), 26% met criteria for concurrent ADHD, 72% had one or more diagnoses of substance abuse or
dependence,
Intervention group – (N=45) Mean age 15.1±1.5 years, 60% (n=27) female, 80% (n=36) white, 11.1% (n=5) living with both biological parents,
Duration of current MDD 99.4±142.9 weeks, duration of current CD 177.9±106.3 weeks, number of current diagnoses 4.4±1.6, number past
suicide attempt 44.4% (n=20),
Comparator group(s) – (N=48) Mean age 15.1±1.3 years, 37.5% (n=18) female, 81.3% (n=39) white, 18.8% (n=9) living with both biological
parents, duration of current MDD 64.2±90.6 weeks, duration of current CD 192.2±124.3 weeks, number of current diagnoses 4.5±1.7, number
past suicide attempt 35.4% (n=17),
Length of follow-up [11] 12 months       Outcome(s) measured [12] Primary – functioning using CGAS and SAS-SR Secondary –
                                         depressive symptoms using K-SADS, BDI-11, LIFE and HAM-D,
                                                            INTERNAL VALIDITY
Allocation [13]            Comparison of study groups           Blinding [15]    Treatment/              Follow-up (ITT) [17]
Participants assembled     [14]                                 Interviewers     measurement bias        Intent to treat with attrition of 6%,
into 9 cohorts and         Groups not significantly different   were blind to    [16]                    Followed up at 6 and 12 months, only
randomisation to           except higher number of females      the              All participants        4 treatment and 2 controls not
intervention occurred      in the treatment group (treated as   participants’    treated and             included in 12 month follow up
within cohort using a      a covariate in analyses where        conditions       measured the same
random numbers table       interaction with gender was non-                      except for
                           significant)                                          intervention
Overall quality assessment (descriptive) [18] good quality study
                                                                   RESULTS

Outcome [19]         Intervention group [20]             Control group [21]                   Measure of effect/effect size
Recovery rates       CWD-A                               LS                                   Posttreatment
for MDD               Posttreatment                      Posttreatment                        OR=2.66, 95% CI 1.03, 6.85, likelihood ratio x2
                      (n=17/44) 44.39%                   (n=9/47) 19%                         [1, N=91]=4.27, p=.039
                     6 month follow-up 54%               6 month follow-up 60%
                     12 month follow-up 63%              12 month follow-up 63%
Recovery rates       CWD-A                               LS                                   Posttreatment
for CD               Posttreatment (n=4/44) 9%           Posttreatment (n=8/47) 17%           OR 0.49 95% CI = 0.14, 1.75, x2[1,N=91]=1.27,
                     6 month follow-up 39%               6 month follow-up 33%                p=.259
                     12 month follow-up 41%              12 month follow-up 39%




Depression in adolescents and young adults                                                                                     825
Diagnostic         CWD-A (n=45)                         LS (n=48)
outcomes for       Baseline (n=45)        100%          Baseline (n=48)        100%
MDD                Posttreatment (n=27/44) 61.4%        Posttreatment (n=38/47) 80.9%
                   6 months (n=19/41)      46.3%        6 months (n=18/45)      40%
                   12 months (n=15/41)     36.6%        12 months (n=17/46)     37%
Diagnostic         CWD-A (n=45)                         LS (n=48)
outcome for CD     Baseline (n=45)        100%          Baseline (n=48)        100%
                   Posttreatment (n=40/44) 90.9%        Posttreatment (n=39/47) 83%
                   6 months (n=28/41)      68.3%        6 months (n=30/45)      66.7%
                   12 months (n=24/41)     58.5%        12 months (n=28/46)     60.9%
Depressive         CWD-A                                LS                                Random effects regression outcomes
symptoms using     Baseline (n=45)    16.6±12.8         Baseline (n=48)     15.4±10.6     Time (bold significant at p<.05)
BDI=11, mean       Posttreatment (n=44) 9.6±10.7        Posttreatment (n=47)11.5±11.1     Baseline-post t -4.89 p.001 r2 0.228
(SD)
                   6 months (n=41)    10.6±11.7         6 months (n=45)     10.2±9.9      Baseline-6mo t -2.96 p .004 r2 0.102
                   12 months (n=41)     9.9±10.4        12 months (n=46)     7.5±8.0      Baseline-12mo t -4.83 p .001 r2 0.230
                                                                                          Group x time (bold significant at p<.05)
                                                                                          Baseline-post t 2.17 p .033 r2 0.055
                                                                                          Baseline-6 mo t 0.34 p .731 r2 0.002
                                                                                          Baseline-12 mo t 0.23 p .821 r2 0.001
Depressive         CWD-S                                LS                                Random effects regression outcomes
symptoms using     Baseline (n=45)        14.2±5.2      Baseline (n=48)        13.8±5.2   Time (bold significant at p<.05)
HAM-D, mean        Posttreatment (n=44)    6.0±6.3      Posttreatment (n=47)    8.3±5.4   Baseline-post t -8.91 p .001 r2 0.472
(SD)
                   6 months (n=41)         5.5±6.3      6 months (n=45)         5.7±6.5   Baseline-6 mo t-7.48 p .001 r2 0 .403
                   12 months (n=41)        5.6±6.4      12 months (n=46)        4.1±5.1   Baseline-12 mo t -8.05 p .001 r2 0.436
                                                                                          Group x Time(bold significant at p<.05)
                                                                                          Baseline-post t 2.09 p .039 r2 0.047
                                                                                          Baseline-6 mo t 0.38 p .701 r2 0.002
                                                                                          Baseline-12 mo t -0.53 p .594 r2 0.003
Functioning        CWD-A                                LS                                Random effects regression outcomes
using CGAS,        Baseline (n=45)       51.6±7.0       Baseline (n=48)     53.0±7.6      Time (bold significant at p<.05)
Mean (SD)          Posttr (n=44)        56.3±10.2       Posttreatment (n=47) 55.1±8.8     Baseline-post t 3.89 p .001 r2 0.145
                   6 months (n=41)      59.1±12.5       6 months (n=45)    58.2±10.0      Baseline-6 mo t 4.53 p .001 r2 0.196
                   12 months (n=41)     60.2±11.8       12 months (n=46) 60.1±11.5        Baseline-12 mo t 4.83 p .001 r2 0.215
                                                                                          Group x Time (bold significant at p<.05)
                                                                                          Baseline-post t -1.51 p .134 r 2 0.025
                                                                                          Baseline-6 mo t -0.93 p .355 r2 0.010
                                                                                          Baseline-12 mo t -0.81 p .421 r2 0.008
Functioning        CWD-A                                LS                                Random effects regression outcomes
using SAS-R,       Baseline (n=45)   35.6±16.9          Baseline (n=48)     32.0±13.9     Time (bold significant at p<.05)
mean (SD)          Posttr (n=44)    26.4±15.6           Posttr (n=47)       30.6±11.9     Baseline-post t -4.04 p .001 r2 0.163
                   6 months (n=41) 28.7±17.4            6 months (n=45)     29.8±15.9     Baseline-6 mo t-2.13 p .036 r2 0.054
                   12 months (n=41) 28.6±15.2           12 months (n=46)    29.5±15.1     Baseline-12 mo t-2.40 p .019 r2 0.067
                                                                                          Group x Time (bold significant at p<.05)
                                                                                          Baseline-post t 2.39 p .019 r2 0.064
                                                                                          Baseline-6 mo t 0.97 p .336 r2 0.012
                                                                                          Baseline-12 mo t 1.39 p .168 r2 0.023
Recurrence rate    CWD-A (n=16)                         LS (n=9)                          (X2 [1, N=25]=0.69, p=.405)
of MDD in 25       25% (n=4)                            11% (n=1)
participants
recovered at
posttreatment
                   Clinical importance (1-4) [26] useful in treating adolescents with     Relevance (1-5) [27]
                   comorbid conditions
Any other adverse effects [28] none stated




826                                                                 Depression in adolescents and young adult
                                                                 EXTERNAL VALIDITY

Generalisability [29] generalisable to highly disordered adolescents with comorbid conditions

Applicability [30]

Comments [31] participants were able to access usual care in conjunction with CWD-A and LS and the two groups did not differ at any
assessment point on external health treatment utilization
ADHD=Attention Deficit Hyperactivity Disorder; CD=Conduct Disorder; CGAS=Children’s Global Adjustment Scale; CWD-A=Adolescent Coping With
Depression Course; HAM-D=Hamilton Depression Rating Scale; K-SADS-E-5=the Schedule for Affective Disorder and Schizophrenia for School Age
Children-Epidemiologic Version 5; LIFE=Longitudinal Interval Follow-up Evaluation; LS=Life skills/tutoring; MDD=Major Depressive Disorder; SAS-
SR=Social Adjustment Scale-Self-Report Version (range 1-5 with higher scores indicating worse functioning);




Depression in adolescents and young adults                                                                                               827
                                                              STUDY DETAILS
Reference [1] (Rohde et al 2006)
Rohde, P., Seeley, J. R. et al (2006). 'Predicting time to recovery among depressed adolescents treated in two psychosocial group
interventions', Journal of consulting and clinical psychology, 74 (1), 80-88.
Affiliation/source of funds [2] Oregon Research Institute, Mesilla Valley Hospital, Kaiser Permanente Center for Health Studies
Supported by a grant from the National Institute of Mental Health
Study design [3]                                     Level of evidence [4]       Location/setting [5]
Prospective inception cohort (for the purposes of    II prognostic               referred from Department of Youth Services of Lane County,
prognosis. Based on an RCT)                                                      Oregon, United States
Patient characteristics [10]                                                                                               Sample size [7]
Mean age15.2±1.4 years, 48% Female, 52% Male, 71% White, 1% African American, 1% Hispanic, 1% Asian                        N= 114 randomised
American, 1% Native American, 25% Other or mixed, 15% living with both biological parents, 21% lived with biological       Length of follow-up
parent and stepparent, 23% lived with biological mother only
                                                                                                                           [11]
                                                                                                                           12 months
Selection criteria
Inclusion criteria: 13 – 17 years of age, current MDD, expected residence in Lane County for next 12 months, minimum English fluency
Exclusion criteria :-charges of first degree assault, robbery, homicide or rape or psychotic symptoms
Prognostic factor(s):                      Data collection method
Demographic variables                      Sex, age, race/ethnicity (White vs non-White)
Depression specific measures               age of first MDD onset and number of prior MDD episodes from K-SADS interview, depression
                                           severity on BDI-II, and suicidal ideation during the past week on a 4 point item.
Broader psychopathology factors            current ADHD, current substance use disorder, or current anxiety disorder on K-SADS
                                            functional impairment assessed by interviewer ratings of current functioning using the CGAS
                                           parent report of problem behaviour on the CBCL
CBT-specific psychosocial factors          negative thoughts on the Automatic Thoughts Questionnaire (ATQ)
                                           dysfunctional attitudes on the Dysfunctional Attitudes Scale
                                           hopelessness during past week on the Beck Hopelessness Scale
Resiliency Psychosocial factors            social adjustment on the Social Adjustment Scale Self-Report for Youth
                                           family cohesion on the Family Environment Scale
                                           coping skills on 17 items (Rohde, Lewinsohn, Tilson & Seeley, 1990)
Treatment interventions                    randomised to either a Coping With Depression (Adolescent) course (CBT) or a Life Skills Training
                                           course to match the nonspecific therapeutic factors associated with CWD-A but without CBT
                                           elements
Potential confounders:
                                                            INTERNAL VALIDITY
Outcome measurement method [12]                                          Comparison of study           Blinding [15]
Time to MDD recovery (8 or more weeks in asymptomatic clinical           groups [14]                   Not stated (participants and
range, defined in the K-SADS/LIFE as having 0 – 2 mild symptoms)         Not stated                    interviewers blinded to treatment
Moderators of treatment effects                                                                        condition, but not stated whether
                                                                                                       outcome measurement was blinded to
                                                                                                       prognostic factors)
Measurement bias [16]                                                    Follow-up (ITT) [17] 94% follow-up at 12 months
Unlikely – controlled for                                                ITT analytic approach
Overall quality assessment (descriptive) [18] Good quality study – low dropout, used ITT analyses, explicit         Quality assessment: ++
reasons for choosing prognostic factors. Did not state whether outcome measurement was blinded to prognostic
factors, but likely to have been given blinding of condition.
                                                                  RESULTS

Significant univariate outcomes for time to MDD        Measure of effect/effect size + 95% CI [22]
recovery
Age of MDD onset                                       HR [1.01, 1.21]
Suicidal ideation                                      HR = 1.47 [1.11, 1.92]
ADHD                                                   HR = 1.89 [1.09, 3.23]
Functional impairment                                  HR = 1.04 [1.01, 1.07]




828                                                                 Depression in adolescents and young adult
CBCL total problem score                              HR = 1.03 [1.01, 1.04]
Negative thoughts                                     HR = 1.01 [1.00, 1.07]
Hopelessness                                          HR = 1.16 [1.04, 1.28]
Family cohesion                                       HR = 0.92 [0.85, 0.99]
Coping skills                                         HR = 0.93 [0.88, 0.98]
Multi variate outcome                                 Measure of effect/effect size + 95% CI [22]
Parent report of total problem behaviours on CBCL     likelihood χ2(1,N=114) = 16.52, p<0.001
Suicidal ideation                                     likelihood χ2(1,N=114) = 6.52, p=0.011
Univariate Moderators of treatment effects            Measure of effect/effect size + 95% CI [22]
Treatment condition x race/ethnicity                  likelihood χ2(1,N=114) =3.91, p=0.048
                                                      Whites: Significant benefit of CWD-A compared to LS (median time to recovery=11
                                                      weeks [6.4, 15.6] vs 27 weeks [14.6, 39.4])
                                                      non –Whites: whereas no benefit (median time 14 weeks [10.0, 30.4] vs 12 weeks [9.9,
                                                      14.1]
Treatment condition x number of previous MDD          likelihood χ2(1,N=114) =3.95, p=0.047
episodes                                              Median time for CWD-A group with recurrent MDD = 6 weeks [3.3, 8.8] vs 38 weeks
                                                      [25.9, 50.1] for LS condition
                                                      First MDD intake: CWD-A median = 13 weeks [5.8, 20.2] vs LS median = 17 weeks
                                                      [13.2, 20.8]
Treatment condition x coping skills                   likelihood χ2(1,N=114) =7.99, p=0.005
                                                      High levels coping skills:
                                                      CWD-A group: median 6 weeks [0.7, 11.3] vs LS group: median 16 weeks [7.2, 24.8]
                                                      Poor coping skills:
                                                      CWD-A group: median 23 weeks [7.8, 38.2] vs LS group: median 27 weeks [18.2, 35.8]
Multivariate Moderators of treatment effects          Measure of effect/effect size + 95% CI [22]
Treatment condition x number of previous MDD          likelihood χ2(1,N=114)=4.33, p=0.038
episodes
Treatment condition x coping skills                   likelihood χ2(1,N=114)=4.54, p=0.033
Conclusion: Suicidal ideation and problem behaviour are the strongest independent pre-treatment variables that predict recovery from MDD.
No. of previous MDD episodes and levels of coping skills moderate the treatment effect.
                                                           EXTERNAL VALIDITY

Generalisability: Unclear how generalisable the population referred compared to consecutive cases with MDD. Setting was in the US, likely to
have reasonable applicability.
Comments: includes the same population as Clarke et al (1992)




Depression in adolescents and young adults                                                                                   829
                                                               STUDY DETAILS
Reference [1] Rossello, J. & Bernal, G. (1999). 'The efficacy of cognitive-behavioral and interpersonal treatments for depression in Puerto
Rican adolescents', J Consult Clin Psychol 67 (5), 734-745. (Rossello & Bernal 1999)
Affiliation/source of funds [2] University Center for Psychological Services and Research, Department of Psychology, University of Puerto
Rico, funded by a national Institute of Mental Health Grant and Support from the University of Puerto Rico, Rio Piedras Campus, Institutional
Funds for Research
Study design [3]         Level of evidence [4]           Location/setting [5] University Center for Psychological Services and Research ,
RCT                      Interventional level II         University of Puerto Rico
Intervention [6] CBT(n=25) – 12 one hour individual sessions over 12            Comparator(s) [8] Wait-list (n=23)
weeks or IPT(n=23) – 12 one hour individual sessions over 12 weeks
Selection criteria
Inclusion criteria – current DSM-III diagnosis of MDD and/or dysthymia, adolescent 13-18 years
Exclusion criteria –serious imminent suicidal risk, psychotic features, bipolar disorders, alcoholism, conduct disorder, drug use disorder,
organic brain syndrome, marked hyperaggression, need for immediate treatment or hospitalization, currently receiving psychotropic medication
of psychotherapy and legal involvement
Patient characteristics [10] (n=71), 13-17 years mean 14.70±1.40, 54% female,
Intervention group – not specified
Comparator group(s) – not specified
Length of follow-up [11]            Outcome(s) measured [12] Primary – functioning using FEICS and SASCA Secondary – depressive
3 months                            symptoms using CDI,
                                                             INTERNAL VALIDITY
Allocation [13]    Comparison of study             Blinding [15]       Treatment/ measurement        Follow-up (ITT) [17]
Randomisation      groups [14]                     Not stated          bias [16]                     To 3 months however wait-list group
not specified      No significant differences                          Groups treated and            commenced treatment after 12 weeks so
                   between groups in any                               measured the same             no follow=up data
                   variables or demographics                           except for intervention
Overall quality assessment (descriptive) [18] average quality study
                                                                   RESULTS

Outcome [19]       Intervention group [20]                 Control group [21]                    Measure of effect/effect size [22]
                                         CBT                                    Wait-list        Pretreatment/posttreatment
Depressive         Pretreatment (n=25) 20.12±6.95          Pretreatment (n=23) 20.13±5.99        F 6.69 (p<.01)
symptoms           Posttreatment (n=21) 13.28±7.61         Posttreatment (n=18) 15.83±6.83       Posttreatment/follow-up
using CDI,         Follow-up (n=11)      8.90±6.84                                               F 0.02
mean and SD
                                         IPT                                                     Pre-post comparison
                   Pretreatment (n=23) 21.21±7.53                                                IPT vs CBT F 2.61
                   Posttreatment (n=19) 10.79±6.51                                               IPT vs control F11.62 (p<.01)
                   Follow-up (n=12) 13.75±9.52                                                   CBT vs control F 2.58 (p<.05)


                                        CBT                                     Wait-list        Pretreatment/posttreatment
Functioning        Pretreatment (n=23) 28.47±7.91          Pretreatment (n=20) 32.30±6.83        F 4.22 (p<.05)
using SASCA        Posttreatment (n=22)31.18±7.07          Posttreatment (n=18) 32.66±3.98       Posttreatment/follow-up
Mean and SD        Follow-up (n=11)     38.36±9.51                                               F 3.58
                                         IPT                                                     Pre-post comparison
                   Pretreatment (n=22) 31.27±6.99                                                IPT vs CBT F 2.02
                   Posttreatment (n=19) 37.00±7.27                                               IPT vs control F 10.62 (p<.01)
                   Follow-up (n=12) 34.16±9.36                                                   CBT vs control F2.12




830                                                                  Depression in adolescents and young adult
                                          CBT                                     Wait-list
Family              Pretreatment (n=23) 18.00±6.45            Pretreatment (n=17) 17.17±6.15            Pretreatment/posttreatment
Functioning         Posttreatment (n=20) 16.85±6.32           Posttreatment (n=18) 18.00±4.48           F 3.01
using FEICS -       Follow-up (n=10)     15.00±5.16                                                     Posttreatment/follow-up
Perceived                                 IPT                                                           F 0.01
criticism
                    Pretreatment (n=22) 18.81±6.87
Mean and SD
                    Posttreatment (n=19) 15.36±4.36
                    Follow-up (n=11)    18.00±6.13
                                        CBT                                       Wait-list             Pretreatment/posttreatment
Family              Pretreatment (n=23) 15.65±4.75            Pretreatment (n=17) 18.00±4.12            F 0.91
functioning         Posttreatment (n=20) 15.85±5.19           Posttreatment (n=18) 17.44±5.62           Posttreatment/follow-up
using FEICS –       Follow-up (n=10) 17.60±4.16                                                         F 0.01
Intensity of
emotional                                IPT
involvement         Pretreatment (n=22) 16.13±4.99
Mean and SD         Posttreatment (n=19) 19.15±6.03
                    Follow-up (n=11)     17.54±4.86




                    Clinical importance (1-4) [26] benefits outweigh risks in treatment groups          Relevance (1-5) [27]

Any other adverse effects [28] none stated
                                                                EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population although cultural specific changes were made to both instruments and
interventions
Applicability [30] significant benefits of both interventions over wait-list

Comments [31] high drop-out rate between posttreatment and follow-up, with no follow-up for wait-list

CBT=Cognitive Behavioral Therapy; CDI=Children’s Depression Inventory (self report - range 0-54 with higher scores indicating greater number of
symptoms); FEICS=Family Emotional Involvement and Criticism Scale; IPT=Interpersonal psychotherapy; MDD=Major Depressive Disorder; SASCA=
Social Adjustment Scale for Children and Adolescents (22 items scoring 0-2 with higher scores indicating better social adjustment);




Depression in adolescents and young adults                                                                                              831
                                                                     STUDY DETAILS
Reference [1] Sanford, M., Boyle, M. et al (2006). 'A pilot study of adjunctive family psychoeducation in adolescent major depression: feasibility
and treatment effect', J Am Acad Child Adolesc Psychiatry, 45 (4), 386-495. (Sanford et al 2006)
Affiliation/source of funds [2] University of Toronto, Ontario, McMaster University, Hamilton, Ontario, Brock University, St. Catherine, Ontario,
University of Western Ontario, London, Hamilton Health Sciences, Hamilton, Canada, supported by a grant from The Hospital for Sick Children
Foundation, Toronto, Ontario, Canada,
Study design [3] RCT             Level of evidence [4] Interventional level II             Location/setting [5] outpatient clinics in Hamilton and
                                                                                           London, Ontario, Canada
Intervention [6] Usual treatment plus Family Psychoeducation 12                Comparator(s) [8] Usual treatment including individual or group
sessions of 90 minutes during the first 6 months after enrolment in the        counselling, and/or drug therapy with supportive case management
study then one booster session after 3 months                                  Sample size [9] (n=15)
Sample size [7] (n=16)
Selection criteria all adolescents attending clinics for depressed adolescents in Hamilton and London, Ontario
Inclusion criteria – meets DSM-IV criteria in the past 6 months according to referring clinician and K-SADS-P, lives with birth, adoptive or
stepparent, baseline assessment completed within 3 months of admission to clinic,
Exclusion criteria – history of mental retardation, pervasive developmental disorder, conduct disorder, anorexia nervosa, nonaffective
psychosis or mania by K=SADS-P interview,
Patient characteristics [10] (N=31) 64.5% (n=20) female, mean age 15.9±1.4 years, 38.7% (n=12) single parent family, mean duration of MDE
58.9±66.7 weeks, mean CGAS score 51.7±9.5,
Intervention group – (n=16), 56.2% (n=9) female, mean age 15.6±1.1 years, 43.7% (n=7) single parent family, mean duration of MDE
58.9±37 weeks, mean CGAS score 48.9±10.4,
Comparator group(s) – (n=15), 73.3% (n=11) female, mean age 16.1±1.6, 33.3 (n=5) single parent family, mean duration of MDE 59.0±88.6
weeks, mean CGAS score 54.7±7.7,
Length of follow-up [11] 9 months after                 Outcome(s) measured [12] Primary – global, social and family functioning using CGAS,
completion of treatment                                 SSAI, and FAD, Secondary – depressive symptoms using RADS and K-SADS-P,
                                                                    INTERNAL VALIDITY
Allocation [13]                     Comparison of study               Blinding [15]             Treatment/ measurement bias          Follow-up (ITT) [17]
Randomisation using random          groups [14]                       Study team                [16]                                 2 experimental and 1
numbers table to determine          The two groups were               members were              No statistical control of testing    control did not
group assignment in blocks          similar in all aspects except     blind to blocking         of multiple outcomes,                complete a
of four, opaque sealed,             the experimental group had        procedure for             Clinicians self rated adherence      posttreatment
numbered envelopes were             a higher number of                randomisation             and fidelity of FPE rather than      assessment however
opened in order after               obsessive-compulsive                                        independent assessor and             all 31 completed a 3
participant completed               disorders and lower but not                                 CGAS was rated by the primary        month follow-up
baseline assessment,                significant mean CGAS                                       clinician rather than                assessment
statistician used had no other      scores.                                                     independent assessor
part in the study
Overall quality assessment (descriptive) [18] average quality study
                                                                         RESULTS

Outcome [19]                     Intervention group [20]                   Control group [21]                           Measure of effect/effect size
Estimated mean outcome           Baseline    79.9                          Baseline 78.2                                [22]
scores                           3 months 70.0                             3 months 73.6
RADS total score                 6 months 65.9                             6 months 71.7                                ES 6mo 0.52 9mo 0.64
Baseline SD 14.4                 9 months 62.8                             9 months 70.3
FAD GF Adolescent                Baseline     2.4                          Baseline       2.6                           ES 6mo 0.1     9m0 0.25
Baseline SD 0.7                  3 months     2.2                          3 months       2.5
                                 6 months     2.1                          6 months       2.4
                                 9 months     2.1                          9 months       2.4
FAD GF Parent                    Baseline     2.2                          Baseline       2.3                           ES 6mo -0.19 9mo -0.19
Baseline SD 0.4                  3 months     2.2                          3 months       2.2
                                 6 months     2.1                          6 months       2.2
                                 9 months     2.1                          9 months       2.1




832                                                                        Depression in adolescents and young adult
SSAI GF adolescent             Baseline     88.7                         Baseline    98.6                           ES 6m0 0.93 9mo 1.14
Baseline SD 12.7               3 months     99.3                         3 months   100.7
                               6 months    103.7                         6 months   101.6
                               9 months    107.1                         9 months   102.3
SSAI GF parent                 Baseline 82.5                             Baseline 97.3                              ES 6mo 0.96 9mo 1.17
Baseline SD 14.3               3 months 94.8                             3 months 99.8
                               6 months 99.9                             6 months 100.9
                               9 months 103.8                            9 months 101.7
                               Clinical importance (1-4) [26]                                                       Relevance (1-5) [27]

Any other adverse effects [28] none stated
                                                                EXTERNAL VALIDITY

Generalisability [29] unsure - one arm of the study was abandoned due to the different approaches of the clinical staff and unfamiliarity with
FPE
Applicability [30] more benefit in the area of functioning than reducing depressive symptoms

Comments [31]

CGAS=Children’s Global Assessment Scale; CSQ=Client Satisfaction Questionnaire; FAD=Family Assessment Device; FAD-GF=Family Assessment
Device General Functioning Subscale Score; K-SADS-P=Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present Episode;
MDD= Major Depressive Disorder; MDE=Major Depressive Disorder; RADS=Reynolds Adolescent Depression Scale; SSAI=Structured Social Adjustment
Interview; SSAI-GF=Structured Social Adjustment Interview Global Functioning Score;




Depression in adolescents and young adults                                                                                             833
                                                               STUDY DETAILS
Reference [1] (Shirk et al 2008)
Shirk, S. R., Gudmundsen, G. et al (2008). 'Alliance and outcome in cognitive-behavioral therapy for adolescent depression', Journal Of Clinical
Child And Adolescent Psychology, 37 (3), 631-639.
Affiliation/source of funds [2] University of Denver, University of Washington Medical School, and UCLA Semel Institute for Neuroscience
and Human Behavior. Supported by a National Institute of Mental Health grant
Study design [3]                                      Level of evidence [4]       Location/setting [5]
Prospective inception cohort                          II prognostic               referred from 4 high schools in Rocky Mountain west, United
                                                                                  States
Patient characteristics [10]                                                                                                 Sample size [7]
36 girls, 18 boys between 14 – 18 years. Mean age = 15.8±1.2 years. 57% European Americans, 43% ethnic minority              N= 50/54
youth, primarily Hispanic (22%), and African American (17%)                                                                  Length of follow-up
63% had cormorbid disorder: generalised anxiety disorder (39%), conduct disorder (33%), social phobia (22%) and              [11]
attention deficit hyperactivity disorder (11%), with another 20% showing elevated conduct symptoms in subclinical
                                                                                                                             Treatment period =
range.
                                                                                                                             12 weeks of CBT
Selection criteria
Inclusion criteria: Adolescents meeting diagnostic criteria for major depressive disorder, dysthymic disorder, depressive disorder not otherwise
specified or adjustment disorder with depressed mood.
Exclusion criteria : Bipolar or psychotic disorder, currently taking medication for depression, were in psychotherapy, or were expelled prior to
beginning treatment.
Prognostic factor(s):                                       Data collection method
Mood, anxiety, disruptive behavior                          Computerised diagnostic interview scale for children (C –DISC)
Depressive symptoms                                         Beck Depression Inventory
Therapeutic alliance                                        Therapeutic alliance scale for adolescents (TASA)

Potential confounders: Not stated
                                                              INTERNAL VALIDITY
Outcome measurement method [12]                         Comparison of study groups [14]                                   Blinding [15]
Depressive symptoms on BDI and C-DISC                   Not stated                                                        Not stated
Measurement bias [16]                                   Follow-up (ITT) [17]
Unlikely                                                Partially completer data only (needed at least one follow-up, but did not need to
                                                        complete study). Imputed data for 7 participants who were missing posttreatment data.
Overall quality assessment (descriptive) [18] Average quality – good description and reliable predictor              Quality assessment: +
variables and outcome measures. However, they did not control for potential confounders such as age/gender
into account, did not report CIs, and there was no mention of blinding of the predictive factors.
                                                                   RESULTS

Multi variate outcome*                                  Measure of effect/effect size + 95% CI [22]
                                                        BDI                                           C-DISC
Pre-symptoms                                            β=0.36, p=0.01                                β=0.27, p=0.06
Sessions                                                β=-0.16, p=0.23                               β=-0.20, p=0.15
Adolescent scored alliance                              β=-0.27, p=0.05                               β=-0.32, p=0.03


Pre-symptoms                                            β=0.38, p=0.01                                β=0.29, p=0.06
Sessions                                                β=-0.13, p=0.38                               β=-0.18, p=0.25
Therapist scored alliance                               β=-0.15, p=0.33                               β=-0.18, p=0.25
Conclusion: More positive early alliance as reported by adolescent was associated with greater change in depressive symptoms at outcome.

                                                              EXTERNAL VALIDITY

Generalisability: Only moderate generalisability given the high proportion of Hispanic and African Americans included in the sample.
Comments:




834                                                                  Depression in adolescents and young adult
                                                               STUDY DETAILS
Reference [1] (Spezzano 2006)Spezzano, M. A. (2006) In Department of Psychology, Vol. Doctor of Philosophy Northcentral University,
Prescott, Arizona, pp. 146.
Affiliation/source of funds [2] Northcentral University, Prescott, Arizona, no funding support identified,

Study design [3] RCT       Level of evidence [4] Interventional level II    Location/setting [5] Monroe Community College, New York
Intervention [6] BLT 30 mins per day for 3 weeks using             Comparator(s) [8] deactivated negative ion generator for 30 mins per day
10,000 lux BLT device                                              for 3 weeks
Sample size [7] N=20                                               Sample size [9] N=20
Selection criteria
Inclusion criteria – DSM-IV-R diagnosis of SAD, BDI-II score of >14 and SPAQ score of >9
Exclusion criteria – using antidepressant medications or herbal products such as St Johns’ Wort within 8 weeks of the study, using illicit drugs,
active alcoholics (self-reported > 14 drinks per week), suicidal tendencies, eye problems or past history of eye surgery,
Patient characteristics [10] N=40, 16 males (40%), 24 females (60%), mean age 19.7±1.3 years, white non-Hispanic 22 (55%), African
American 10 (25%), Hispanic 8 (20%),
Intervention group – N=20, 9 males (45%), females 11 (55%), mean age 19.75±1.4 years, white non-Hispanic 10 (50%), African American 5
(25%), Hispanic 5 (25%),
Comparator group(s) – N=20, 7 males (35%), 13 females (65%), mean age 19.7±1.2 years, white non-Hispanic 12 (60%), African American 5
(25%), Hispanic 3 (15%),
Length of follow-up [11] duration of treatment only       Outcome(s) measured [12] Secondary – depressive symptoms using BDI-II and
                                                          SIGH-SAD
                                                             INTERNAL VALIDITY
Allocation [13]        Comparison of study       Blinding [15]                   Treatment/                 Follow-up (ITT) [17]
Randomisation          groups [14]               Double blind – participants     measurement bias           2 control participants failed to
using a computer       No significant            and research assistant who      [16]                       complete treatment, all participants
after participants     differences between       completed assessments all       Groups treated and         included in analysis
completed              groups on any             blind to treatment              measured the same
assessments            variable                  allocation                      except for intervention
Overall quality assessment (descriptive) [18] average quality

                                                                   RESULTS

Outcome [19]              Intervention group [20]         Control group [21]             Measure of effect/effect size [22]
Depressive symptoms                 BLT (N=20)                     Control (N=20)
using SIGH-SAD mean       Baseline 39.2±6.1               Baseline 38.9±4.9              Between group differences at
and SD                    Week 1 20.7±11.1                Week1      36.7±5.6            week 1 (SE (diff) =2.9, p<.0001)
                          Week 2 13.6±12.9                Week 2     36.1±6.0            Week 2 (SE (diff) =3.3, p<.0001
                          Week 3 12.6±12.4                Week 3     35.7±6.9            Final testing (SE (diff) =3.3, p<.0001)
                                                                                         Differences in Control group means-
                                                                                         Baseline to week 1, SE (diff) =1.9 n.s.
                                                                                         Week 1 and week 2, SE (diff) =1.6 n.s.
                                                                                         Week 2 and final, SE (diff) =1.4 n.s.
                                                                                         Differences between means in BLT group
                                                                                         Baseline to week 1, SE (diff) =1.8 p<.0001
                                                                                         Week 1 and week 2, SE (diff) =1.5 p<.0001
                                                                                         Week 2 and final, SE (diff) =1.3 n.s.
                                                                                         Paired sample t-test for control group between
                                                                                         baseline and final testing (t (17) =2.62, p<.01)
                                                                                         Paired sample t-test for BLT group between baseline
                                                                                         and final testing (t (19) =8.86, p<.0001)




Depression in adolescents and young adults                                                                                      835
Depressive symptoms          Baseline 27.0±6.6                  Baseline      25.6±5.6           Control group mean scores between baseline and final
using BDI-II, mean and       Final    9.1±10.0                  Final         24.4±6.9           testing (SE (diff) =1.7, n.s.)
SD                                                                                               BLT group mean scores between baseline and final
                                                                                                 testing (SE (diff)= 1.6, p<.0001)
                                                                                                 BLT vs control groups mean scores –
                                                                                                 Baseline (SE (diff) =2.0, n.s.)
                                                                                                 Final (SE (diff)= 2.8, p<.0001)
                                                                                                 BLT within group baseline to final p<.0001
                                                                                                 BLT vs control final scores p<.0001
                                                                                                 Paired sample t-test for control group between
                                                                                                 baseline and final testing (t (17) =1.94, p<.05 both 1-
                                                                                                 tailed)
                                                                                                 Paired sample t-test for BLT group between baseline
                                                                                                 and final testing (t (19) =8.49, p<.0001, both 1- tailed)
Remission criterion          80% remission at final             0% remission in final            Chi square X2 (1,N-38) =24.9, p<.0001
50% reduction in             testing                            testing                          Ordinal regression X2 (1,N=38) =31.7, p<.0001
SIGH-SAD symptoms


                             Clinical importance (1-4) [26] fast response easy                   Relevance (1-5) [27]
                             inexpensive intervention with minimal medical supervision
Any other adverse effects [28] none stated

                                                                  EXTERNAL VALIDITY

Generalisability [29] likely generalisable to target population

Applicability [30] benefits outweigh harms

Comments [31]

BDI-II= Beck Depression Inventory 2nd Edition (range 0-39 with higher scores indicating greater number of symptoms of depression); BLT= Bright Light
Treatment; GSS= Global Seasonality Score; SAD= Seasonal Affective Disorder; SIGH-SAD= Structured Interview Guide for the Hamilton Depression
Rating – Seasonal Affective Disorder; SPAQ= Seasonal Pattern Assessment Questionnaire;




836                                                                         Depression in adolescents and young adult
                                                                 STUDY DETAILS
Reference [1] (Treatment for Adolescents with Depression Study Team 2004; Domino et al 2008; Emslie et al 2006a; Kennard et al 2006)
(Vitiello et al 2006)

Treatment for Adolescents With Depression Study Team (2004). 'Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for
Adolescents With Depression: Treatment for Adolescents With Depression Study (TADS) Randomized Controlled Trial', JAMA: Journal of the
American Medical Association, 292 (7), 807.

Domino, M. E., Burns, B. J. et al (2008). 'Cost-effectiveness of treatments for adolescent depression: results from TADS', Am J Psychiatry, 165
(5), 588-596.

Emslie, G., Kratochvil, C. et al (2006). 'Treatment for Adolescents with Depression Study (TADS): safety results', Journal of the American
Academy of Child and Adolescent Psychiatry, 45 (12), 1440-1455.

Kennard, B., Silva, S. et al (2006). 'Remission and residual symptoms after short-term treatment in the Treatment of Adolescents with
Depression Study (TADS)', Journal of the American Academy of Child and Adolescent Psychiatry, 45 (12), 1404-1411.

Vitiello, B., Rohde, P. et al (2006). 'Functioning and quality of life in the Treatment for Adolescents with Depression Study (TADS)', Journal of
the American Academy of Child and Adolescent Psychiatry, 45 (12), 1419-1426.

Affiliation/source of funds [2] Duke Clinical Research Institute, Duke University Medical Center and National Institute of Mental Health
Supported by the National Institute of Mental Health. Lilly Inc provided fluoxetine and matching placebo under an independent educational grant
to Duke University.
Study design [3]                    Level of evidence [4]                  Location/setting [5]
RCT                                 Interventional level II                Clinics, advertisements in media, primary care physicians, other
                                                                           mental health clinicians, schools and juvenile justice facilities at 13
                                                                           academic and community clinics
Intervention [6] Fluoxetine (SSRI):                                        Intervention [6] Fluoxetine and CBT:
10 mg/day for 1 week, 20 mg/day after 1 week, increased to                 All the components from the medication alone and CBT alone groups.
maximum of 40 mg/day by week 8.                                            Sample size [7] 107
Sample size [7] 109
Intervention [6] CBT skills-oriented treatment: psychoeducation            Comparator(s) [8] Placebo: pill matching appearance of fluoxetine
about depression, goal-setting, mood monitoring, increasing pleasant
activities, social problem-solving, cognitive restructuring                Sample size [9] 112
15 x 50 – 60 minute sessions over 12 weeks
2 parent-only sessions
1 – 3 joint parent and adolescent sessions
Sample size [7] 111
Selection criteria
Inclusion criteria –Primary DSM-IV diagnosis of MDD, aged between 12 and 17, ability to receive care as outpatient, CDRS-R total of ≥45; IQ
of ≥80; not taking antidepressants, depressed mood present in at least 2 of 3 context (home, school, among peers). Concurrent stable
medication for ADHD permitted.
Exclusion criteria –Current or past diagnosis of bipolar disorder, severe conduct disorder, current substance abuse or dependence, pervasive
developmental disorder(s), thought disorder, concurrent treatment with psychotropic medication or psychotherapy outside of study; 2 failed SSRI
trials, a poor response to clinical treatment containing CBT for depression, intolerance to fluoxetine, confounding medical condition, non English
speaking patient or parent, and/or pregnancy or refusal to use birth control. Patients were excluded if deemed high risk of suicide (previous
attempt, suicidal ideation, intent or plan).
Patient characteristics [10] Mean age = 14.6±1.5 years, 45.6% male, 73.8% white, 12.5% black, 8.9% Hispanic, 52.1% cormorbid for at least
1 other psychiatric disorder, 13.6% with cormorbid ADHD, median family income between US$50 000 and US$74 000, 41% in single-parent
household, 27% suspended or expelled from school
Fluoxetine group – 43.1% with psychiatric comorbidity, 5.5% with dysthymia, current MDD episode duration, median: 38 wks
Fluoxetine + CBT group –55.7% with psychiatric comorbidity, 10.3% with dysthymia, current MDD episode duration, median: 48 wks
CBT group – 58.2% with psychiatric comorbidity, 15.5% with dysthymia, current MDD episode duration, median: 52 wks
Placebo group - 51.4% with psychiatric comorbidity, 10.7% with dysthymia, current MDD episode duration, median: 36 wks
Length of follow-up [11] Treatment length:         Outcome(s) measured [12] Primary –remission (no longer meeting MDD diagnosis on DSM-
12 weeks                                           IV criteria using K-SADS-P/L) functioning on the CGI, CGAS and PQ-LES-Q,
                                                   Secondary – depressive symptoms on RADS, suicidal ideation on the Suicidal Ideation
                                                   Questionnaire- Junior High School version (SIQ-Jr), adverse events (as reported by therapist
                                                   or pharmacotherapists),
                                                   Cost effectiveness - cost per quality adjusted life year




Depression in adolescents and young adults                                                                                          837
                                                             INTERNAL VALIDITY
Allocation [13]             Comparison of study            Blinding [15] Patients        Treatment/ measurement bias           Follow-up (ITT)
Computerised stratified     groups [14]                    and clinicians in             [16] Treatment bias unlikely.         [17]
randomisation, permuted     No statistically significant   fluoxetine and placebo        There is the possibility of bias in   Yes, ITT
blocking.                   differences on                 groups blinded except in      the measurement of adverse
                            demographics or baseline       emergencies.                  events, as CBT therapists did
                            variables                      Independent evaluators        not report as many as
                                                           blinded for all conditions.   pharmacotherapists, including
                                                                                         far fewer than placebo.
Overall quality assessment (descriptive) [18] High quality study
                                                                   RESULTS
Mean daily dose (for flexible dose studies):
Outcome [19]     Fluoxetine               Fluoxetine + CBT         CBT                     Placebo                Measure of effect/effect size
                                                                                                                  [22] [95%CI]

Resolution of    78.6%                    85.3%                    61.1%                   60.4%                  Wald χ2 =22.6, df = 3, p<0.001
depression (no                                                                                                    Fluoxetine vs placebo: OR = 2.4
longer meeting                                                                                                    [1.27, 4.67], p=0.007
criteria for                                                                                                      Fluoxetine + CBT vs placebo:
MDD on K-                                                                                                         OR = 4.1 [2.00, 8.44], p = 0.001
SADS-P/L)
                                                                                                                  CBT vs placebo: OR = 1.0
                                                                                                                  [0.52, 1.77], p=0.89
                                                                                                                  Fluoxetine + CBT vs CBT: OR =
                                                                                                                  4.3 [2.06, 8.94], p=0.0004
                                                                                                                  Fluoxetine + CBT vs fluoxetine:
                                                                                                                  OR = 1.7 [0.79, 3.61], p=0.18
                                                                                                                  Fluoxetine vs CBT: OR = 2.5
                                                                                                                  [1.31, 4.93], p=0.006
Depressive       Pre: 58.94±4.00          Pre: 60.79±4.89          Pre: 59.64±4.52         Pre: 61.18±4.27        Fluoxetine + CBT vs placebo:
symptoms on      Post: 36.30±8.18         Post: 33.79±8.24         Post:                   Post:                  p=0.001 Effect size = 0.98
CDRS – R                                                           42.06±9.18              41.77±7.99             Fluoxetine vs placebo: p=0.003,
(scale: 17 –                                                                                                      Effect size = 0.68
113)                                                                                                              CBT vs placebo: p=0.94, Effect
                                                                                                                  size = -0.03
                                                                                                                  Fluoxetine + CBT vs CBT:
                                                                                                                  p=0.001
                                                                                                                  Fluoxetine + CBT vs fluoxetine:
                                                                                                                  p=0.11
                                                                                                                  Fluoxetine vs CBT: p=0.003
Depressive       Pre: 76.96±9.57          Pre: 80.12±9.23          Pre: 78.69±10.59        Pre: 81.26±9.22        Time x Treatment interaction:
symptoms on      Post:                    Post: 56.95±12.24        Post: 67.96±14.18       Post:                  F(3,380) = 10.32, p=0.001
RADS (scale:     60.58±13.07                                                               66.68±11.41            Fluoxetine vs placebo: p=0.34
30 – 120)                                                                                                         Fluoxetine + CBT vs placebo:
                                                                                                                  p=0.001
                                                                                                                  CBT vs placebo: 0=0.21
                                                                                                                  Fluoxetine + CBT vs fluoxetine:
                                                                                                                  p=0.002
                                                                                                                  Fluoxetine + CBT vs CBT:
                                                                                                                  p=0.001
                                                                                                                  Fluoxetine vs CBT: p=0.03




838                                                                   Depression in adolescents and young adult
Response (1:     60.6% [95%CI 51,   71.0% [95%CI 62,   43.2% [95%CI 34,   34.8% [95%CI 26,   Treatment group:
very much        70]                80]                52]                44]                Wald χ2=0.14, p=0.001
improved or 2:                                                                               Fluoxetine vs placebo: p=0.001,
much                                                                                         Effect size = 0.58, NNT = 4 [3,
improved on                                                                                  8]
CGI)
                                                                                             Fluoxetine + CBT vs placebo:
                                                                                             p=0.001, Effect size = 0.84,
                                                                                             NNT = 3 [2, 4]
                                                                                             CBT vs placebo: p=0.20, Effect
                                                                                             size = 0.20, NNT = 12 [5, 23]
                                                                                             Fluoxetine vs fluoxetine + CBT:
                                                                                             p=0.11
                                                                                             Fluoxetine vs CBT: p=0.001
                                                                                             Fluoxetine + CBT vs CBT:
                                                                                             p=0.01
Functioning      Baseline (n=109)   Baseline (n=107)   Baseline (n=111)   Baseline (n=112)   Treatment x time p<.0001 for
using CGAS       49.5±7.26          50.0±7.52          50.0±7.58          49.1±7.59          CGAS
total score      Week 6 (n=99)      Week 6 (n=98)      Week 6 (n=97)      Week 6 (n=95)      COMB superior to placebo on
mean + SD                                                                                    CGAS p<.0001
                 59.9±10.58         62.4±11.2          56.7±9.66          57.0±9.22
                 Week 12 (n=98)     Week 12 (n=95)     Week 12 (n=90)     Week 12 (n=96)     Fluoxetine superior to placebo
                                                                                             on CGAS p=.0381
                 62.1±11.91         66.6±11.91         60.0±11.47         59.3±12.72
                                                                                             COMB better than fluoxetine on
                                                                                             CGAS p<.0450
                                                                                             Fluoxetine superior to CBT on
                                                                                             CGAS p=.0032
                                                                                             (F=8.83, df=3,422 p<.0001)
Contrast                                                                                     Slope contrast
between                                                                                      Active vs Placebo
treatment                                                                                    Active vs PBO df 1,1045    F
groups on the                                                                                16.66 p<.0001
random-effects
regression                                                                                   FLX vs PBO df 1,1051
Model Slope                                                                                  F 4.31 p .0381
on CGAS                                                                                      CBT vs PBO df 1,1042
                                                                                             F 0.77 p.3805
                                                                                             Active treatments
                                                                                             COMB vs CBT df 1,1037
                                                                                             F 24.59 p<.0001
                                                                                             COMB vs FLX df 1,1046
                                                                                             F 4.03 p .0450
                                                                                             FLX vs CBT df 1,1043
                                                                                             F 8.73 p .0032
Functioning      Baseline (n=104)   Baseline (n=102)   Baseline (n=102)   Baseline (n=106)   Treatment x time p<.0001 for
using PQ-LES-    44.9±7.77          42.5±9.16          42.9±9.40          42.5±9.18          PQ-LES-Q
Q                Week 12 (n=96)     Week 12 (n=86)     Week 12 (n=88)     Week 12 (n=94)     COMB superior to placebo on
                 51.2±10.43         54.7±11.21         47.4±10.84         48.2±9.91          PQ-LES-Q p<.0001
                                                                                             COMB better than fluoxetine on
                                                                                             PQ-LES-Q p=.0004
                                                                                             (F=6.81, df=3,422, p<.0001)




Depression in adolescents and young adults                                                                  839
Contrast                                                                                                        Slope contrasts
between                                                                                                         Active vs Placebo
treatment                                                                                                       COMB vs PBO df 1,374
groups on the
random-effects                                                                                                  F 15.34 p.0001
Regression                                                                                                      FLX vs PBO df 1,371
Model Slope                                                                                                     F 0.13 p.7215
on PQ-LES-Q                                                                                                     CBT vs PBO df 1,375
                                                                                                                F 0.54 p.4630
                                                                                                                Active treatments
                                                                                                                COMB vs CBT df 1,376
                                                                                                                F 21.09 p<.0001
                                                                                                                COMB vs FLX df 1,372
                                                                                                                F 12.80 p.0004
                                                                                                                FLX vs CBT df 1,373
                                                                                                                F 1.19 p.2766
Suicidal          Pre: 21.81±15.68        Pre: 27.33±18.51         Pre: 21.91±16.28        Pre: 24.20±16.46     Random regression analysis:
ideation on       Post:                   Post: 11.79±11.69        Post: 11.40±10.44       Post:                Time x Treatment interaction:
SIQ-Jr (scale:    14.44±11.13                                                              15.01±11.05          F(3,409) = 3.59, p=0.01
0 – 90)
                                                                                                                Fluoxetine vs placebo: p=0.36
                                                                                                                Fluoxetine + CBT vs placebo:
                  Adjusted means:         Adjusted means:          Adjusted means:                              p=0.02
                  Post: 0.05              Post: 0.28               Post: 0.33                                   CBT vs placebo: p=0.76
                                                                                                                Fluoxetine + CBT vs fluoxetine:
                                                                                                                p=0.002
                                                                                                                Fluoxetine + CBT vs CBT:
                                                                                                                p=0.05
                                                                                                                Fluoxetine vs CBT: p=0.22
                                                                                                                Adjusted means show a
                                                                                                                discrete but small protective
                                                                                                                effect of CBT on suicidal
                                                                                                                ideation
Suicide related   9/109 (8.26%)           6/107 (5.61%)            5/111 (4.50%)           4/112 (3.57%)        Fluoxetine vs placebo: OR =
adverse                                                                                                         2.43 [0.73, 8.14]
events                                                                                                          Fluoxetine + CBT vs placebo:
(worsening                                                                                                      OR = 1.60 [0.44, 5.85]
suicidal                                                                                                        CBT vs placebo: OR = 1.27
ideation,                                                                                                       [0.33, 4.87]
suicide
attempt or                                                                                                      SSRI vs no SSRI: OR = 1.77
both)                                                                                                           [0.76, 4.15]
                                                                                                                CBT vs no CBT: OR = 0.85
                                                                                                                [0.37, 1.94]
Costsa (2003      $1,714±$2,743           $3,322±$1,983            $2,678±$1,933           $1,433±$2,643
US$)              (range: $426 –          (range: $390 -           (range: $396 -          (range: $109 -
                  $23,924                 $15,292                  $17,190)                $23,838)
Cost per          $23,737                 $123,143                 $9,210,622                                   Cost per QALY for fluoxetine +
QALY              (range: $15,825 -       (range: $82,096 -        (range: $2,140,347 -                         CBT vs fluoxetine = $458,818
compared to       $23,989)                $246,287)                $18,421,435)                                 Range: $305,829 - $917,637
placebo
Clinical importance (1-4) [26] Clinically important differences for full range of          Relevance (1-5) [27] Evidence of a benefit on patient
estimates for fluoxetine and fluoxetine + CBT compared to placebo. No clinically           relevant outcomes.
important differences between CBT and placebo.
Any other adverse effects [28]

Psychiatric-related adverse events
                  Fluoxetine              Fluoxetine + CBT         CBT                    Placebo               Fluoxetine vs placebo:
mania/hypoma      4                       1                        0                      2                     OR = 2.57 [1.11, 5.94]
nia




840                                                                    Depression in adolescents and young adult
irritable/           5                      2                        0                      1                       Fluoxetine + CBT vs placebo:
depressed                                                                                                           OR = 1.45 [0.58, 3.58]
mood
agitation/           2                      1                        0                      3                       CBT vs placebo:
restlessness                                                                                                        OR = 0.1 [0.01, 0.84]
anxiety/panic        2                      0                        1                      0
sleep                4                      7                        0                      2                       Fluoxetine alone had the
                                                                                                                    highest levels of psychiatric
fatigue/             4                      3                        0                      2                       adverse events, followed by
sedation                                                                                                            fluoxetine + CBT, then CBT
Other                2                      2                        0                      1                       alone.
                                                                                                                    All patients with reported
Total                23 events,             16 events                1 event                11 events
                                                                                                                    adverse events responded to
                     20/109 patients        12/107 patients          1/111 patients         9/112 patients          treatment modification or
                                                                                                                    discontinuation.
Non-                 3 cases sedation       2 cases diarrhoea        1 case vomiting        2 cases upper           Those treated with fluoxetine
psychiatric          6 cases upper          5 cases insomnia                                abdominal pain          had adverse events at least
adverse              abdominal pain         4 cases vomiting                                1 case diarrhoea        twice as often as those in the
events               2 cases diarrhoea                                                      1 case influenza        placebo group.
                     2 cases influenza                                                      1 case insomnia         None of the patients receiving
                                                                                                                    CBT alone reported non-
                     3 cases insomnia                                                       2 cases sinusitis       psychiatric adverse events.
                     4 cases sinusitis                                                      1 case vomiting
                     2 cases vomiting
Spontan-             81 events              61 events                9 events               60 events               Far fewer AEs reported by CBT
eously               35/109 patients        37/107 patients                                 34/112 patients         therapists than
reported AEs                                                                                                        pharmacotherapists
                                                                EXTERNAL VALIDITY

Generalisability [29] Limited generalisability due to the recruitment strategy (advertising), and exclusion criteria, excluding those highly suicidal,
with conduct disorder, and active substance misuse.
Applicability [30]

Comments [31] Fluoxetine + CBT more effective than fluoxetine alone, which is more effective than CBT alone, which is equal to placebo.




Depression in adolescents and young adults                                                                                          841
                                                                STUDY DETAILS
Reference [1] Wood, A., Harrington, R. & Moore, A. (1996). 'Controlled trial of a brief cognitive-behavioural intervention in adolescent patients
with depressive disorders', J Child Psychol Psychiatry 37 (6), 737-746 (Wood et al 1996)
Affiliation/source of funds [2] Royal Manchester Children’s Hospital, UK, supported by a grant from the Mental Health Foundation,


Study design [3]                           Level of evidence [4]                Location/setting [5]
RCT                                        Interventional level II              Royal Manchester Children’s Hospital, UK
Intervention [6] 5-8 Individual sessions of DTP involving cognitive        Comparator(s) [8] 5-8 individual sessions of RT (methods used are
therapy, social problem solving and dealing with issues such as lack       described in ‘Progressive relaxation training’ Bernstein & Borkovec
of sleep and activity                                                      1973 – not specified in this article)
Sample size [7] n=26                                                       Sample size [9] n=27
Selection criteria-,
Inclusion criteria – children and adolescents 9-17 years of age with DSM-III-R MDD or RDC minor depression and a MFQ ≥15
Exclusion criteria – psychotic disorder, inpatients taking or likely to require antidepressants, unable to complete the questionnaires, autism,
attending a special school because of learning problems, major physical illness or epilepsy
Patient characteristics [10]
Intervention group – N=24, 67% (n=16) female, mean age 13.8±1.7 years, median duration of present episode 42 (3-156) weeks, total SAICA
score mean 2.4±0.6,
Comparator group(s) – N=24, 71% (n=17) female, mean age 14.6 ±1.6, median duration of present episode 34 (4-250) weeks, total SAICA
score mean 2.5 ±0.7,
Length of follow-up [11] 6 months                 Outcome(s) measured [12] Primary – functioning Secondary - depressive symptoms,


                                                              INTERNAL VALIDITY
Allocation [13]          Comparison of study groups         Blinding [15]            Treatment/ measurement             Follow-up (ITT) [17]
Randomisation            [14]                               Assessor blinded to      bias [16]                          53 entered study, 48
method not               No significant differences         treatment group          Groups treated and measured        completed, (2 DPT and 3
specified                between group except for           allocation               the same except for                RT withdrew), 53
                         intervention                                                intervention                       assessments completed
                                                                                                                        at follow-up
Overall quality assessment (descriptive) [18] good quality study
                                                                     RESULTS

Outcome [19]                     Intervention group [20]                     Control group [21]                          Measure of effect/effect
Clinical outcome measures                                                                                                size [22]
for completers                                              DTP                                        RT                (t=3.0, df=46, p<.01)
CGI (mean and SD)                Posttreatment            2.2±0.9            Posttreatment           3.1±1.1


Clinically remitted              Post treatment (n=13/24)    54%             Post treatment (n=5/24)    21%
                                 3 month follow-up (n=10/22) 45%             3 month follow-up (n=5/22) 25%
                                 6 month follow-up (n=12/22) 54%             6 month follow-up (n=8/21) 38%


MFQ-C score reaches              Post treatment (n=18/24)    75%             Post treatment (n=8/24) 33%                 F =8.0, p<.01 df 1,
clinical significance            3 month follow-up (n=15/22) 68%             3 month follow-up (n=7/21) 33%
                                 6 month follow-up (n=14/21) 67%             6 month follow-up (n=16/22) 73%

Reliable Change Index score      Post treatment (n=12/24)    50%             Post treatment (n=5/24) 21%
(MFQ-C) >1.96                    3 month follow-up (n=14/22) 64%             3 month follow-up(n=7/21) 33%
                                 6 month follow-up (n=11/21) 52%             6 month follow-up (n=11/22) 50%
Intent to treat sample                                                                                                   N=53, df 1, F=6.2, p=.02
Posttreatment MCQ-C score                                                                                                Paired t-test, t=3.6,
and 6 month follow-up                                                                                                    df=21, p<.01
                                 Clinical importance (1-4) [26] the DTP group had a greater reduction in                 Relevance (1-5) [27]
                                 depressive symptoms than the control




842                                                                    Depression in adolescents and young adult
Any other adverse effects [28] none stated

                                                               EXTERNAL VALIDITY

Generalisability [29] likely generalisable to the target population

Applicability [30] significant short term benefits of treatment

Comments [31]

CGI=Clinical Global Improvement; DTP=Depression Treatment Programme; GAS=Global Assessment Scale; MDD=Major Depressive Disorder;
MFQ=Mood and Feelings Questionnaire; RDC=Research Diagnostic Criteria; RT=Relaxation Training; SAICA= Social Adjustment Inventory for Children
and Adolescents




Depression in adolescents and young adults                                                                                           843

				
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