Statistics on Major Depressive Disorder Point prevalence of

Document Sample
Statistics on Major Depressive Disorder Point prevalence of Powered By Docstoc
					            Statistics on Major Depressive Disorder



• 	 Point prevalence of about 5% (2.3 - 7.9)


... 	 Lifetime prevalence of about 17.1 %


•   Higher in women (21.30/0) than men (12.7%)


• 	 Approx. 80% will have recurrence
• 	 Average 4 episodes or more in a lifetime
• 	 Average duration of an episode is 20 weeks

• 	 Approx. 70% of those who take the medication will have
    positive results

• A large number of patients either discontinue medications,
    do not take medications as prescribed or are· prescribed
    inadequate doses of antidep·ressant medication
CRITERIA FOR MAJOR DEPRESSIVE EPISODE

PERIODS OF SADNESS ARE INHERENT ASPECTS OF THE HUMAN EXPERIENCE

5 OF THE FOLLOWING 9lN THE SAME TWO WEEK PERIOD
MUST HAVE A LIMBIC SYMPTOM
MUST BE CLINICALY SIGNIFICANT
NOT BETTER ACCOUNTED FOR BY ANOTHER DISORDER' DRUGS'
MEDICAL CONDITION .


LIMBIC
   • DEPRESSED MOOD
   • . LOSS OF lNTEREST , PLEASURE IN ACTMTIES (ANHEDONIA)


CORTICAL
  • DECREASED CONCENTRATION
  • DECREASED SELFWORTH' GUILT
  • SUICIDAL IDEATION·' THOUGHTS OF DEATH



HYPOTHALAMIC·

  •   WEIGHT CHANGE' APPITITE
  •   LOSS OF ENERGY
  •   SLEEP CHANUE
  •   PSYCHOMOTOR CHANGE



lNTHE MEDICALLY ILL, FOCUS ON:
       ./ !NDECISIVENESS
       ./ ANHEDONIA
       ./ SELF WORTH
       ./ SUICIDAL IDATION


DIAGNOSIS OF "DEPRESSIVE DISORDER DUE TO A MEDICAL CONDITION" IS
RESERVED FOR SITUATIONS WHEN A DIRECT PHYSIOLOGIC EFFECT OF THE
CONDITION IS THOUGHT TO BE RESPONSABLE FOR THE MOOD SYMPTOMS
Figure L Texas Medication Algorithm Project (TMAP): 

Maj9r Depressive Disorder Without Psychotic Features' 





'Adap~ from Crismon et aI.' The TMAP a1gorithms are in the public
domain, and this figure may be reproduced without permission, but
with the appropriate citation. Abbreviations: ECT = electroconvulsive
               =                                     =
therapy, MAOI monoarnineoxidase inhibitor, SSRI selective
serotonin reuptalce inhibitor, TeA = tricyclic antidepressant
bSSRIs preferred.                                        _
"Consider TCA or venlafaxine if not tried.
           Any stage(s} can
           be skipped depending
          . on the clinical picture
                                                                                                     Remission·····~




                                               ffi-···P:erti:al Response




                                                                                                                        , 'Con'linuation   I       ,
                                                                                                                       c,            ., -      1




                                                                                                                                                       ············i
                                                                                                                                                                  I
'This material is i~ the p~blic ~o~~in and may be rep:~duced witho.ul permiss!on ?f cos~ Abbreviations: ECT:: electroconvulsive therapy. 

MAOI :: Monoamme oXIdase mhibltor, rTMS :: repeUtIve transcranlal magnettc stImulatIon, SR = sustained release, SSRI '" selective serotonin 

reuplake inhibitor. TCA :: tricyclic antidepressant, VNS = vagus nerve stimulation. XR = extended release. 

bSSRIs include fluoxetine. sertraline. paroxetine, and citalopram.                            .

'Lithium, thyroid. buspirone.        .

1I(:0nsider TCA or venlafaxine if not tried. 

<Most studied combinations, 

                                        Table 2.1 Models of psychotherapy and putative mechanisms of change
     ----~----------------------
       Psychotherapy model 	                             PUtative mechanism of change
       Cognitive-behavioural therapy (CBT) 	            Challenging and changing negative cognitions alters the way that individuals construe their interpersonal
                                                        world and promotes more adaptive patterns.      .
       Interpersonal psychotherapy (1P1) 	               Improving the quality ofrelationships and addressing socially avoidant patterns allows individuals to
                                                         benefit from the stimulation and validation of social interaction.
       Briefdynamic psychotherapy (BDP) 	                Identifying and discussing internal conflicts, often around dependence and intimacy, frees individuals to
                                                          more effectively make choices in how to conduct their lives,                              '
       Supportive psychotherapy (spn 	                    Improving immediate adaptation to the current life situation through the conscious process ofleaming
                                                          problem-solving skills reduces stress and builds self-confidence.
       Cognitive-behavioural analytic system of           Understanding how individuals create'their own difficulties, especially in relationships, allows them to
       psychotherapy (CBASP)                                   .
                                                        . alter the situations that make them unhappy. This model was specifically desilmed fOT MM"nh mit"
                                                                           .
48S 	                       CLINICAL GUIDELINES FOR THE TREATMENT OF DEPRESSIVE DISORDERS                                                Vol 46, Suppl 1




                                                                                                        I     Lcvel I Evidence       I
                                                             I"linc          0
                                                           mcdication
                                                                                                        r..    ___ _



                                                                                                              Level.'! Evid('lll'C


                                                           Response?         a
                                      Partial                                      Full


                                                                  None

                                                             ,..
                           "                                  ..
                                                       r ­ Switch ­ 10
                   .............-..V
                       Augment     A                                                            I   Milintenance          I0
                        Lithium
                           T3                              to another
                                                            first-line
                                                           medication




                            '----------1"'".-t Response? tl<l~t-_-_-_ _ _ _ _ _ _ _ _--,
                                             J
                                                     "'1              . I"
                                      Partial                                        Full


                                                                  None
                                                                                                              ,..
                                                                                                I Maintenance I



                       Augmcllt
                                                        r - ".. ­
                                                             Switch      I
                                                                                            .........
                                                                                            "
                                                                                            i   Comhine
                                                                                                        ~".~~~."    ...
                                                                                                                    l0
                        Lithium                             to a drug                           with a drug
                           T3                                with a                               with a
                       Buspirone                            different                            different
                        Atypical                           mechanism                            mechanism
                      antipsychotic
                        Psycho­
                       stimulant


                                                             .                                      .
 Figure 4.1 	 Evidence-based algorithm for treatment of refractory major depression. Note that treatment may not be sequential-any step of the
              algorithm can be bypassed depending on the clinical stale of the patient.




 The Canadian Journal oCPsychiatty
June 2001                                       , IV. Medications and Other Biological Treatments 	                                            49S




                      Notes to Figure 4.1 Evidence-based algorithm for treatment of refractory major depression

    I. First-line medication is chosen based on clinical factors              • 	 Augmentation strategies using lithium and T3 are the best
    such as previous response, depressive subtype, comorbidity,                   validated treatments.
    side effects, and potential for drug-drug interactions. Doses
                                                                              • 	 Side effects ofaugmentation, especially with lithium, are
    should be increased every 2 to 4 weeks as necessary to                        generally gr~ter than with antidepressant monotherapy.
    achieve optimal response.
                                                                              • 	 Benefits of augmentation include building on a partial re­
    2. At each decision point, when there is partial or no 
                      sponse, rapid onset of effect, allowing a longer time on
    response, the clinician should 
                                              the initial antidepressant, maintaining therapeutic opti.
                                                                                  mism with patients.
    '. 	Reevaluate diagnostic issues (for example, subtype, 

        comorbidity, bipolarity, substance abuse) 
                           • 	 Benefits of switching to another monotherapy include:
                                                                                  simpler treatment, fewer side effects, no concerns about
     • 	 Reassess suicide risk                                                    drug-drug interactions, ,better compliance.
     • 	 Consider adding psychotherapy (see Section V)
                                                                              6. Maintenance medications should be continued at the
     • 	 Consider electroconvulsive therapy (ECT) (especially if              same dose for at least 6 months. Longer-term maintenance (at
         high suicide risk, severe or chronic illness, psycl10tic fea­
                                                                              least 2 years) should be used for frequent episodes (2 or more
         tures,physical deterioration, or pregnancy).
                                                                              in 5 years), recurrent episodes (3 or more, lifetime),cbronic
     3. Definitions ofresponse have usually used scores from 
                episodes, severe episodes (for example, with psychotic
     standardized rating scales like the Hamilton Depression 
                symptoms or marked suicidal ideation), difficult-to·treat
     Rating Scale (HDRS). GeneraJly, minimal improvement is 
                 episodes, and in older-age patients,
   . defined as less than 20% reduction in HDRS scores compared
     with baseline; partial remission as 20% to 50% reduction in              7. After an unsuccessful augmentation, consider combining'
     HDRS score, or greater than 50% reduction in HDRS but                    another antidepressant for partial or no resp'onse.
     residual scor~ still outside the normal range; remission as a
                                                                               8. 	 After 2 second-generation antidepressants with different
     score within the normal range. Busy clinicians may be more
                                                                             , neurochemical actions have been tried, consider a TCA
     likely to use global rating scales like the Clinical Global
                                                                               (nortriptyline or desipramine) with therapeutic drug
     Impression Improvement Scale--very much improved
                                                                               monitoring (sefum levels), or a monoamine oxidase inhibitor
     (remission), much improved or minimally improved (partial
                                                                              (MAOI).
     remission), not improved or worse (no response).
    4. Switching to another antidepressant with a different                   9: There is now considerable theoretical rationale to .
    neurochemical action is generally recommended if there is no              combine antidepressants with different neurochemical actions
    response after optimizing the first antidepressant. Switching             for monotherapy nonresponders. However, there is as yet
    from one selective serotonin reuptake inhibitor (SSRI) to                 only limited evidence to support combination antidepressant
    another can be considered, but response rates are higher in               treatment. Only open-label case series (Level 3 evidence) are
    patients who are SSRI-intolerant rather than nonresponsive.               available. This limited evidence suggests that SSRI plus
                                                                              desipramine, SSRI plus mocloberilide, SSRI plus bupropion,
     5. Many experts hold offaugmentation until after the                     bupropion plus venlafaxine, TCA plus venlafaxine,
     second antidepressant; however, there is some opinion that               mirtazapine combinations, and the older TCA plus MAOI
     augmentation can be tried ifthere is a partial response with             combination may be beneficial for refractory depression.
     the first medication. In this situation, only validated                  Limitations ofcombination antidepressants include increased .
     augmentation strategies with Level I evidence (lithium, T3  )            side effects, potential drug-drug interactions, higher cost,
     should be considered. Note that lithium and T3 augmentation              and the possibility ofresponse to monotherapy with the new
     has only been studied with tricyclic antidepressant (TCAs)               antid~ressant.
     and SSRIs.
     Factors to consider in deciding between augmentation and                 10. Adding augmentation to combination antidepressants can
     switching after the first antidepressant:                                be considered for the mosfrefractory patients.




                                                                                                              The Canadian Joumal   of Psychiatry
               Table 4.6 Criteria for levels of evidence and
                  lines oftreatment recommendations
  Level 01 evidence          Criteria
                             Metaanalysis or replicated randomized controlled
                             trial (ReD that includes a placebo condition
  2                          At least I RCT with placebo or active
                             comparison condition
  3                          Uncontrolled trial with JO or more subjects
  4                          Anecdotal case reports
  Line 01 Treatment          Criteria
  first-line                 Level I or Level 2 evidence plus clinical support
  Second-line                Level 3 evidence or higher' plus clinical support
  Third-line                 Level 4 evidence or higher' plus clinical support
  Not recommended            Level I or Level 2 evidence for lack ofeffiCacy
"rreatmenlJ; with higher levels of evidence may be listed as lower lines of IreIItment
due to clinical issues such as side effoct or safety profile.
        Recommendations for Managing Nonresponse
                 to an Antidepressaot
                                                              (s.. Table 4.6)

Once an lllitidepressant is selected, an initial improvement (at least 20%
reduction in depression scores) should be seen within 3 to 4 weeks.
Otherwise, the following interventions are indicated:
First-line trcatments        • Optimize lI)i: antidepressant by increasing
                               the dose as tolerated (Level 2 evidence).
~econd-line treatments       • Switch to an antidepressant with a differ­
                               ent neurochemical action (Level 2 evi­
                               dence).
                             • Augment with lithium or triiodothyronine
                               (TJ)(Levell evidence).
Third-line treatments        • Switch to an antidepressant wIth a similar
                               neurochemical action (Level 2 evidence).
                             • Augment with huspirone or an atypical
                        ..
                               antipsychotic such as olanzapine (Level 2
                               evidence)•
                             • Combine with another antidepresSant
                               (Level 3 evidence).
Not recommended              .. Augment with pindolol (Level 2 evi•
                               . dence).
Figure 6. Symptom and Side Effect Sheet (2-sided)*

                               (Front)                                                                             (Sack)
     In the last week, the symptoms of my illness were:                                                           Symptoms
      Not Present    Mild     Moderate     Severe Very Severe
          (0)        (1)        (2)          (3)      (4)
     List the 3 most bothersome symptoms in the last week:
     1.
     2.                                                                           Not steeping or       , Restlessness or slowness       Can't make decisions
                                                                                sleeping too much           observable by others         and can't concentrate
     3.
                                                                                                         '~
     Things I did lor me: _ _ _ _ _ _ _ _ _ _ _ __
                                                                                                               1;'11,  I~
                                                                                                             ~~_.II
                                                                                                           "I" ',I      "'... ""
                                                                                                                            ""c..
                                                                                                          /~~       ,/1 .
                                                                                                           / //

     The side effects of my medication were:
                                                                                   Feeling down         Blaming yourself too much      'Fatigue or 'loss of energy
      Not Present    Mild     Moderate     Severe Very Severe                         all day             and feeling worthless             nearly every day
          (0)         (1)       (2)          (3)            (4)
     List the 3 most bothersome side effects in the last week:
     1.
     2.
     3.                                                                        Significant change in       Thinking about death    .     No longer interested
     Things I did lor me: _ _ _ _ _ _ _ _ _ _ _ __                              weight or appetite              frequently                in lavorile actMtes

                                                                                        Medications can cause side eHects in many parts of the body. 

                                                                                         Some may go in time, others can be treated by your doctor. 


                                                                                                                                  Eyes
     List medications that you are currently taking:                                                                              Homnone System
     1. _______~_____ 3. ______~----                                                                                              Skin
                                                                                                                                      Nervous System
     2.                             4. _..,.-_ _ _ _ __

     About how long have you been taking each medication?                                                               -1--""';'- Digestive System
     WeeksiMonthslYears                                                                                                 +--- Urinary System


                                                                                  Ask your doctor about side effects that need to be. reported immediately I

                                                                                              Illegal drugs and alcohol may increaSe the side          tG\
                                                                                             effects of medications or keep them from working.         ~

*This material is in the public domain and may be reproduced without permission.
                                                   Dysthymia
                                                       E~
                                                       .2'1::
                                                        Q.!e
                                                        E!I)
                                                       jj)m
                                                                                lime (y)
                                                       Depressed mood persistent lor most of the time,
                                                       01 at least 2 years' duration


                                                   Chronic Major Depression
                                                        E~
                                                       .2'1::
                                                        Q.II)
                                                       ~~
                                                       mm
                                                                              lime (y)
                                                       Major depression of at least 2 years' duration


                                                   Double Depression




                                                       Major depression superimposed on dysthymia


                                                   MDE Without Complete Interepisode Recovery
                                                      E ~ MOE           MOE
                                                        ~i
                                                        E~
                                                       ($(J)
                                                                                lime(y)
                                                         Recurrent episodes 01 major depression without
                                                       , full recovery between episodes, duration of illness
                                                         ~2 vears
Table 5. Reported Pharmacokinetic Parameters of Newer Antidepressants*
                                                             Volume of                                              Average Steady-State
Drug                    Bioavailability Plasma Protein       Distribution       Clearance      Half-Life (h)        Plasma Concentration
(active metabolite)          (%)         Binding (0/0)         (Ukg)              (LIb)     Mean (h) Range (h)                (n~mL)
Fluoxetine                   80                 95                25             10-36        45      24-144                  90-300
  (Norfluoxetine)                                                                                    200-223                  70-260
Sertraline                 > 44                 98                25               96         26      22-36                   20-200
  (Desmethy Isertraline)                                                                      71      62-104        > parent concentration
Paroxetine                 >64                  93               17            36-167         18       7-{i5               10-600
FJuvoxamine                > 53                 77              >5          80 (33-220)       15       9-28                20-500
Citalopram                   95                 82               14          26 (23-38)       33      23-:45               40-300
Bupropion                    90                 80              27-60         116-362         10       4-23                  5-50
  (Hydroxybupropion)                                                                          21                          200-1500
Venlafaxine                  92                 27               2-23            40-129                 2-11               50-150
  (O-desmethyl)                                 30               9-13                                 6.5-16              200-400
Nefazodone                 >20                  99             0.2-1.0                                  2-8               150-1000
Mirtazapine                  50                 85               4.5                                   13-34                20-40
Reboxetine                 >60                  97               0.5               1.7                 12-16               50-160
*Data from references 12. 17.42. and 47.




         Table 3; Neurotransmitter Reuptake and Neuroreceptors Involved in the Actions of Antldepressants*
                        ·5-HT         NE          DA
         Drug         Reuptake Reuptake Reuptake 5-HT;A                5-HT2C 5-HT)            (X,               Histamine,
         SSRr
         Bupropion                     V           V
         Venlafaxine       V           V
         Nefazodone        V.                                 V                                V
         Mirtazapine                                          V          V            V
         Reboxetine                    V
                                                  =
         *Abbreviations: 5-HT .. serotonin; NE norepinephrine; DA dopamine. =
         '''SSRJ'' comprises f1lloxetine, sertraline, paroxetine. f1uvoxarnine, or citalopram.
Table 4. Antidepressant Effects on Sleep Parameters*
Drug             Continuity        SWS          REM        Sedation
SSRI'           No change       No change     Decrease No significant
                  or decrease     or decrease              effect
Bupropion      Decrease         No change     Increase No significant
                                                           effect'
Venlafaxine NO                  ND            Decrease ,Moderate
                                                           effect
Nefazodone Increase             No change     Increase No significant
                                                           effect
Mirtazapine Increase           Increase       Decrease Moderate
                                                           effect
Reboxetine No change           ND             NO         No significant
                  or decrease                              effect
*Adapted from references 38-40. Abbreviations: SSRI = serotonin
selective reuptake inhibitors; SWS = slow wave sleep; REM =rapid
eye movement; ND no data available.
'Complete data are unavailable for all SSRIs but are presumed to show
minor differences.




                                                   Figure 2. Reported Ranges of Elimination Half-Lives for
                                                   Newer Antidepressants*
                                                               Auoxetine             j-               •        {-I
                                                               Sertraline           ~
                                                                                    i
                                                                                          (-I
                                                              Paroxetine        4         •
                                                      ..
                                                      "E Fluvoxamine
                                                       t il
                                                      II> 

                                                      Q)      Citalopram
                                                                                .....;.
                                                                                     I


                                                                                    70­
                                                      is.
                                                      Q)       Bupropion        ~-)
                                                      -0                             I
                                                      E Venlafaxine         ~
                                                      «                      I·
                                                              Nefazodone ~,
                                                              Mirtazapfne ~

                                                              Reboxetine
                                                                            o   -'   I
                                                                                    24 48, 72 96 120 144 168 192 216 240
                                                                                              Hail-life (h)
                                                    "The double arrow for each drug refers to parent drug half-life, and
                                                    arrows in parentheses show metabolite half-life. The broken line
                                                   ,denotes the value of 24 hours.



                                                 Table 2. SSRI Discontinuation Characteristics*
                                                 • Discontinuation occurs with all" selective serotonin
                                                   . reuptake inhibitors (SSAls)
                                                 • Symptoms have been reported after therapy as brief as 3
                                                    weeks                   '             '           '
                                                 • Average time to onset after discontinuation:
                                                         fluvoxamine 2 days
                                                         sertraline      3.6 days
                                                         paroxetine      3.5 days
                                                         fluoxetine      6.4 days
                                                 • Typical symptoms include dizziness, fatigue, nausea,
                                                    myalgias, paresthesias, agitation
                                                 • Treatment is usually unnecessary; tapering the agent
                                                    slowly over 1 to 2 weeks is recommended for all patients
                                                   "Data from Therrien and Markowitz 1997.                       .
"




    June 2001                                                    IV. Medications and Other Biological Treatments 	                                                                         458



                                      Table4.2b Frequency of side effects to selective serotonin reuptake inhibitors (SSRIs)
                                                      and novel,antidepressants at therapeutic dosages'
     Reaction                                                 SSRIs

                           Citaloprarn      FJuoxctine      Fluvoxamine       Paroxetine      Sertraline     Neliozodone     Trazodone      Bupropion         Venlafaxine      Mirtazapine
       CNS effects
       Drowsiness,
       sedation
                                0                0                0                0              0              0               '1<
                                                                                                                                                 •                 0                '1<'


       Insomnia                 0               Of                0                0              0               •              •               0                Of
                                                                                                                                                                                    •
       Excitement,              •                •                0                •              0               •             _k              Ok                Ok
                                                                                                                                                                                    •
       hypomania'
       Disorientation!
       confusion
       Headache                 0
                                                 0

                                                 0
                                                                 '.
                                                                  0
                                                                                   •
                                                                                   0              0            '0
                                                                                                                 0

                                                                                                                                 •
                                                                                                                                                 •
                                                                                                                                                 0
                                                                                                                                                                   •
                                                                                                                                                                   0
                                                                                                                                                                                    •
                                                                                                                                                                                    •
       Astheoia,
       fatigue
                                0                0                0                0              •             0                0
                                                                                                                                                 •                 0                0

    ,' Anticllolinergic
       effec1s
                                0                0                0                0              0              0               0               0                 0
       Dry mouth
       Blurred vision           •                •                •                •               •             0               .1              0                 •
                                                                                                                                                                                    ~

                                                                                                                                                                                    0
       Coostipation             •                •                0                r:i             •             0               •               0                 0                0
       Sweating                 0                •                0                0               •              •                              0                 0                •
       Delayed
       mict\lritionb
                                •                •                •                 •              •                              •              •                                  •
       Extr!Ipyramidal
       effec1s
       Unspecified
       Tremor
        CardioVll!lcular
        effec1s
                                0                .'
                                                 0
                                                                  •
                                                                  0                0
                                                                                    •              •
                                                                                                   0
                                                                                                                                 .a
                                                                                                                                 •
                                                                                                                                                 •
                                                                                                                                                 0
                                                                                                                                                                   •
                                                                                                                                                                   •                •
        Orthostatic              •               0                •                0               0              0             0'"              .0               O·                •
        hypotension!
        dizziness
        Tachycardia.
        palpitations
        ECG changes'
                                .'               .'               .'               .' .'                          .'             •
                                                                                                                                 •
                                                                                                                                                 •                 •                •
        Cardiac
        arrhythmia
                                                 .h
                                                                                    •                                            ••              •
        Gl distress              0               0                 ~               0               lri            0              0               0                 ~
                                                                                                                                                                                    •
        Dermatitis,
        rasb
                                                  •                •                •              •                                             •                 •
        Weigbtgaln
        (over 6 kg)
                                 ol               .i                               .1              .1
                                                                                                                                 •              .•i                .1                ~



        Sexual
        dillturbances
                                 •               ~;                I<               aJ             aJ                            oJ              *PJ               ~j


        Seizuresd                                 •                                 •                                             •              +'I
                                                                                                                                                                                     •
     *< 2%, •   ~ 2%, 0 ~ 10%, !l! ~ 30%, - None reported in literature perused. 

     'More likely in patients with bipolar illness; b Primarily in the elderly; "ECG abnonnalities usuany without cardiac injury; dIn patients without epilepsy; risk increased with 

     elevated plasm. levels; 'Decreased heart rate reported; 'Especially ifgiven in the evening; 'Tardive dyskinesia reported (rarely); "slowing of sinus node and atrial dysrhythmia; 

     Weigbt loss reported initially; JPriapism reported; 'Less likely to precipitate maoia; 'Found to lower iutrsocular pressure; "'Less frequent if drugs given after meals; "Patients with 

     preeXisting cardiac disease have a 10",1, incidence ofprematore ventricular contractions; "Hypertension reported; 'Improved sexual functioning; "Higher incidence ifdoses used 

     above 450 mg daily ofbupropion or in' patients with bulimia; 'Sedation decreased at higher doses (above 15 mg); 'Adapted from Bezchlibnyk-Butler and Jeffiies (77). 



    the index antidepressant, potential side effects ofnew treat-	                                       clinicians would generally switch patients who have not re­
    ments, and previous medication history.                   "	                                         sponded to an optimized and tolerated dose ofthe first dtug to
                                                                                                         a medication in a different class-for example, from an SSRI
                                                                                                         to a serotonin norepinephrine reuptake inhibitor (8NRI), a se~
    9. Howeffective are switching strategies?                                                            rotonin antagonist and reuptake inhibitor (8ARI), a nora­
     Antidepressants can be switched either within the same medi­                                        drenaline and dopamine modulator (NDM) or a
     cation class (or neurochemical action) or to a different class                                      noradrenaline reuptake inhibitor (NRl).
     (or neurochemical action). Switching within the class is a"                                         When considering a switch to another antidepressant,
     poor choice with the TCAs, but can be an effective strategy                                         drug-drug interactions must be considered in choosing a
     for 8SRls. The response rate when switching to another SSRI                                         starting dosage. For example, a switch from fluoxetine, a long
     is generally better when the first SSRI is poorly tolerated                                         half-life SSRI that significantly inhibits C¥P2D6, to a TCA
     (66%) than when the patient is refractory{48%)(ll I). Expert                                        that requires this iso"enzyme for metabolism (for example,

                                                                                                                                                  The Canadian Journal of Psychiatry
46S                                  CLINICAL GUIDELINES FOR THE TREATMENT OF DEPRESSIVE DISORDERS                                                             Vol 46, Suppl1



 Table 4.2c. Frequency of side effects to monamine oxidase inhibitors and reversible inhibitor of because most ofthe studies in­
       .               MAO-A antidepressants at therapeutic dosages k                             . volve small sample sizes and
 ~--------------------------------                                                                                                          report augmentation of TCAs
 Reaction  Isocarboxazid j Phenelzine Tranylcypromine Moclobemide
                                                                                                                                            more often· than SSRIs or other
 CNS effects                                                                                                                                agents. There. are also few


                                                   .'
                                                   •                                                                        •
       Drowsiness. sedation                                                 0                       0                                       placebo-controlled trials of
      . Insomnia                                                           o·                      o·                      o·               augmentation strategies, and
       Excitement, hypomania'                      •                        0                       0                       0               there are even fewer direct
       Disorientation/confusion                    •                        •                       •                       •               comparisons of different aug­
                                                                                                                                            mentation strategies.
       :a;"'dache                                  0                        •                                               0
       Asthenia. fatigue                           •                                                                                        Lithium augmentation has the
                                                                                                                                            most evidence supporting its
 Anticholinergic effects
       Dry mouth                                   0                                                o                       o               use. Two metaanalyses have
                                                                                                                                            shown that lithium augmenta­
       Blurred vision                              •                        o                       •                       o               tion is effective in about 60%
       Constipation                                •                        o                       •                       •               of .fefractory patients
       Sweating                                     •                       •                                               •               (112,113). Lithium should be
       DeJayed micturitionb                        •                        •                       •                                       given at dosages of greater
  Extrapyramidal effects                                                                                                                    than 750 mg daily, or at a dos­
       Unspecified                                  •                       o                                                               age that achieves serum levels
                                                                                                                                            of at least 0.5 meqIL. A sug­
       Tremor                                      0                        o                       •                       •               gested dosage schedule is 600
  Cardiovascular effect.
                                                                                                                                            mg daily for 1 week, increas­
       Orthostatic hypotension!                    0                        o                       o                       o               ing to 900 mg daily for 1 week,
       dizziness
                                                                                                                                            and then titrating to adequate
       Tachycardia, palpitations                                                                                            •               serum levels for another week.
       EeG changes·                                 •                       ••                                              •               Ifthere is no response after 3 to
       Cardiac anhythmia                            •                                                •                      •               4 weeks, then alternate strate­
  Gldistres.                                       0                        o                       •                       o               gies can be used. Lithium aug­
  Dermatitis, rash                                  •                                                                       •               mentation. is associated with
  Weight gain (over 6 kg)                           •                       o                                                               the usual side effects oflithium
  Sexual disturbances
                                                    •                       <J}                                                             use.
                                                                                                                               Triiodothyronine (T3, liothy­
• < 2%•• :t 2%, 0 :t 100/., !I<:t 30%, ~ None reported in literature perused.                                                  ronine) has also been shown to
'More likely in patienlS with bipolar !I1ness;!>Primarily in the elderly; 'BeG abnonnallties usually without cardiac injury; "In patienlS
                                                                                                                               be effective in placebo­
without epilepsy; 'Especially ifgiven in the evemng; fDecreased beart rate reported; 'Shortened QTc interval; "l'riapism reported;
                                                                                                                               controlled RCTs. One RCT
'May have anticonvulsalJt activity; ~ot currently available in Canada; 'Adapted from aezcbliboyk-Butler and Jeffiies 07}.
                                                                                                                               found comparable efficacy be­
                                                                                                                               .tween T3 and lithium, both of
desipramine) indicates that lower-than-usual starting dosages
                                                                                                 which were superior to placebo (114). T3 also appears to be
of the TCA should be used. This is also a situation Where
                                                                                                 more effective than thyroxine (T4) (115). A metaanalysis,
plasma TCA monitoring would be appropriate.
                                                                                                 however, showeq equivocal results, due to the inlluence of a
Generally. there is no need to stop one antidepressant for a                                     singlelarger negative study (116). T 3 is usually started at a
time before starting another. With most drugs, the first antide­                                 dose of25 mcg daily and increased to 50 mcg after I week, if
pressant can be tapered while starting another, but patients                                     necessary. With no response at the higher dose for 2 weeks,
may experience .additive side effects in the overlap period.                                     another strategy should be used. T3is generally well tolerated.
For a patient who has not tolerated the first antidepressant, it
may be wise to provide a washout period, allowing the side
effects to dissipate before starting a second antidepressant.                                    Both lithium and T3 studies have primarily involved patients
Classic MAOls require a 2-weekmedication washout prior to                                        who were refractory to monotherapy with TeAs or MAOls.
starting another antidepressant, while a 3-day washout for                                       Only 2 studies examined lithium augmentation in SSRI non­
moclobemide is recommended (see Table 4.5).                                                      responders (with citalopram [117] and fluoxetine [118]).
                                                                                                 There is only limi ted evidence to date to support lithium or T3
                                                                                                 augmentation ofthe novel-action antidepressants.
10. How effective are augmentation strategies?                                                   Other strategies have focused on SSRI nonresponders. Buspi­
Augmentation strategies are among the best validated phar­                                       rone, a partial postsynaptic 5-HT 1A agonist with catechola­
macologic treatments for refractory depressive disorders.                                        mine effects, was beneficial in a number of open-label
There are, however, significant limitations to our knowledge,                                    studies, but a placebo-controlled RCT was negative, likely


  The Canadian Jouma1 of Psychiatty
44S                                 CUNlCA'L GUIDELINES FOR THE TREATMENT OF DEPRESSIVE DISORDERS                                                                Vo146, Suppll




                                 Table 4.2a Frequency of side effects to cyclic antidepressants at therapeutic dosagesl 


 Reaction              Amitriptyline" Clomipramine       Desipramine "Dollepin       Imipramine     Nortriptyline    Protriptyline   Trimipramine                    Maprotiline 


 CNSelJects
 Drowsiness,
 sedation
                                              •               •                           o               •               •                                o              o
 Insomnia                   •                o                •              •            o                               o                                o
 Excitement,
 hypomania' 

                                                              •                           o               •               o                                •              •

 Disorienlntion!
 confusion 

                            o                 •                              •            •               o                                o               •              •

  Headacbe                   •                •                                           o                                                •               •              •
  Asthenia, tatigoe         o                 •               •              •            o               o               o                •               •              •
  Anticholinergic 

  effects 

  Drymo\Jtb                                                   o                                           o               o                o
  Blurred vision             o               o                 •             o            o               •               o                •               •              o
  Constipation               o               o                 •             o            o               o               o                o                              o

  Sweating                   o               o                 •             •            o                               o                •               •              •

  Delayed
  micturitionb
                             •                •                                           o                                                                o
             •
  Extrapyramidal 




                             .'
  effects 

  Unspecified
  Tremor                     o
                                              .'
                                              o                •
                                                                             .'
                                                                             •            o               o               •                o
                                                                                                                                                           Ii'
                                                                                                                                                           •
                                                                                                                                                                          •
                                                                                                                                                                          o
  Cardiovascular 

  effects 

  Orthostatic
  hypotension! 

                             o                o                •             o                            •               o                o               o
             •
  dizziness 

  Tachycardia,
  palpitations 

                             o              '0                 o             •            o               •                •               •               o              •

  BCG cbanges<                                                                                                                                                            .r

  Cardiae 

  arrhythmia 

                             •                •                •             •             •              •                •               •
  GI distress                •                                 •                          o                                                                •              •
  Dennatitis. rasb           •                •                •                           •                                                               o              o
  WeigIIt gain
  (over 6 kg) 

                                              o                •             o             o               •                               o                              o


   Sexual 
                   •                                •              •                                                                            •
   disturbances 


                                              ••                                                                                                           .              .'
 • <: 2%•• ~ 2%,    0 ~ 10%, $ ~ 300/., -None reported in literature perused.                                                                                                    "
 'MOre likely in patients with bipolar illness; "Primiuily in the elderly; 'BCG abnormalities usually without cardiac injury; "In plllients without epilepsy; "Tardive dyslcinesia
 reported (rarely); fConduction delays: increased PR, QRS or QT, interval; 'Higher incidence if dose above 250 mg dally clomipramine, 225 roB daily maprotillne or 300 mg daily
 amoxapine; ~o effect on REM sleep; 'Adapted from B.ozchlibnyk·Butler and Jeffries (J7).


 abuse) and treatment issues (for example, adherence, and side                                 that by itself is not an antidepressant, while combination
 effects), including suicide reassessment. Psychotherapy                                       strategies involve adding a second antidepressant. Given the
 strategies can be considered at this time (see Section V).                                    paucity ofcomparative data to inform the clinician whether to
 For phannacologic strategies, the clinician has the choice of                                 swi tch or augment/combine, the psychiatrist and patient must
 switching, augmenting; or combining antidepressant medica­                                    consider several factors, including the side-effect burden ofa
 tions. Augmentation strategies involve adding a medication                                    particular medication, whether there is a partial response to


  The Canadian Journal of Psychiatry

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:7
posted:7/5/2011
language:English
pages:14