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 40 wk
Severity (CGI-S) F(1,419)=73.35, p31
Melancholic features (CDRS-R) F(1,408)=30.76, p1
Hopelessness (BHS) F(1,407)=12.70, p9
Adolescent treatment expectancy F(5,371)=3.17, p$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, p13 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
(p0.05
± 7.4 BDI – university v high school a:
HAM-D: 3.7 ± 1.9 Z=2.0, p0.05
HAM-D – university v high school:
Z=2.6, p0.05
PSI difference v BDI follow-up: �������� = - 0.41, n=22,
Pearson’s correlation coefficient:
PSI difference v HAM-D follow-up: �������� = - 0.26,
p0.05 (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 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 .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; P14 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, p1.96 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