Stress Generation and Recurrent Depression: The Role of Differential Treatment Response
Condition: Depression; Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 1

Summary: 
      Depression affects over one million people in Canada, resulting in $14.4 billion per year in
      costs to Canadian society. In order to prevent this often lifelong disorder, it is critically
      important to identify risk factors for the recurrence of depression. A crucial force in
      maintaining depression is the generation of stressful life events. That is, individuals who
      have a history of depression are likely to generate the very events that precipitate future
      depressive episodes (e.g., relationship break-up, fired from job, conflicts with the law) due
      to negative personality characteristics and disrupted social support networks resulting from
      previous episodes. This project is the first to test a model that examines the role of
      negative personality, low social support, and childhood abuse and neglect as risk factors for
      the generation of stressful life events that predict future depression. We will test this
      model in a group of patients meeting formal criteria for depression who will be treated and
      then followed up for 12 months or until depression recurrence. With this long-term design we
      will be in a unique position to understand how depression is maintained over time, thus
      suggesting important treatment strategies to prevent depression recurrence.
    

Detailed description: 
      The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research
      Programme (TDCRP) (Elkin et al., 1989; Sotsky et al., 1991) compared three forms of treatment
      for depression -- imipramine plus clinical management (IMI-CM), cognitive behaviour therapy
      alone (CBT), interpersonal therapy alone (IPT) -- against a placebo control plus clinical
      management (PLA-CM) condition. These three treatments were found equally effective in the
      treatment of the index episode of depression when compared to the placebo control (Elkin et
      al., 1989). The results from the TDCRP study also indicated that patient characteristics,
      irrespective of treatment modality, were predictive of treatment effects. Six patient
      dimensions -- social dysfunction, cognitive dysfunction, expectation for improvement,
      endogenous features, double depression and duration of current episode -- were all found to
      be significant predictors of outcome (Sotsky et al., 1991). Patient characteristics were also
      found to be associated with differential outcome depending on treatment modality. Elevated
      social dysfunction, for example, interfered with successful outcome in IPT, whereas cognitive
      dysfunction hindered successful outcome with CBT. Cognitive dysfunction also predicted poor
      treatment response in the IMI-CM condition. Cognitive vulnerability would be expected to
      mediate response to treatment in CBT, as the presumed mechanism of change is dysfunctional
      depressogenic cognitions (e.g., Beck et al., 1979; Whisman, 1993). The finding that cognitive
      vulnerability was also implicated in treatment response to a pharmacological intervention is
      without theoretical explanation or specific causal agency.

      The purpose of the proposed research is to further examine the relationship between treatment
      outcome and patient characteristics associated depression. In particular, the relationship
      between treatment outcome and two personality/cognitive characteristics implicated as
      vulnerability factors for depression - self-criticism and dependency - will be explored.

      The first aim of the proposed investigation is to examine the relationship between change in
      self-criticism and dependency and the relationship of this change to treatment response and
      reduction in severity of depression. Mode-specific outcome measures will be administered to
      outpatients with major depression randomly assigned and treated with CBT, IPT or PHT.

      The second aim of this study is to examine the issue of whether successful targeting of
      either cognitive dysfunction in CBT or interpersonal functioning in IPT will result in a
      reduced risk for relapse and/or recurrence of a major depressive episode.

      We believe that the dependent type, who centres their definition of self entirely around
      issues of affiliation with others, would be more likely to show changes related to such
      themes in a therapeutic intervention specifically designed to address interpersonal problems.
      In contrast, the self-critic who defines self primarily around issues related to achievement
      and engages in excessively harsh and unrealistic self-appraisal would respond best to an
      intervention that targeted these punitive cognitions.

      HYPOTHESES/RESEARCH QUESTIONS

      Prediction of Treatment Outcome (Objective 1):

      Two sets of hypotheses are proposed. In all analyses the DEQ will be used to assess
      self-criticism and dependency. The first set of hypotheses involves mode specific treatment
      outcomes and the second set of hypotheses address differences in the mechanisms of change
      across the treatments.

      The first set of hypotheses are: (a) all treatments will be equally effective in the
      treatment of the index episode, (b) baseline self-criticism and dependency scores will
      predict outcome in all treatments, with higher self-criticism and dependency scores related
      to poor outcome, (c) CBT will demonstrate greater specificity for targeting self-criticism
      than will either PHT or IPT, (d) IPT will demonstrate greater specificity for treating
      interpersonal functioning than will either PHT or CBT, (e) PHT will demonstrate greater
      specificity for treating endogenous symptoms than will either CBT or IPT.

      The second set of hypotheses are: (a) change in self-criticism scores and dysfunctional
      cognitions will mediate a positive treatment response in CBT but not in IPT or PHT, (b)
      change in dependency scores and interpersonal deficits will mediate positive treatment
      response in IPT but not in CBT or PHT, (c) change in endogeneity will mediate positive
      treatment response in PHT but not in CBT or IPT.

      Prediction of Relapse and Recurrence (Objective 2):

      It is hypothesized that: (a) CBT and IPT will produce a lower rate of relapse and recurrence
      than PHT because of the greater reduction in stable dysfunctional cognitions related to
      either self-critical and/or interpersonal vulnerabilities; (b) in cases where interpersonal
      vulnerabilities are predominant, IPT will produce lower rates of relapse and recurrence than
      either CBT and PHT, in cases where self-critical vulnerabilities are predominant, CBT will
      produce lower rates of relapse and recurrence than either IPT or PHT.
    

Intervention name(s): Cognitive Behavioral Therapy; Interpersonal Therapy; Antidepressant medication
Intervention type(s): Behavioral; Behavioral; Drug
Intervention description(s): All patients randomized to this condition will receive 16 consecutive weeks of manualized cognitive-behaviour therapy provided by either M.S.W or Ph.D. psychotherapists trained and certified in CBT. Treatment will be conducted according to the manualized CBT treatment for depression outlined by Beck and colleagues (Beck et al., 1979), and consistent with the protocol administered in the NIMH study.; All patients randomized to this condition will receive 16 consecutive weeks of manualized interpersonal psychotherapy conducted by M.S.W., Ph.D., or M.Ed. psychotherapists trained and certified in IPT.; Patients patients randomized to this condition will be treated for 16 weeks with different classes of anti-depressant medications, using standardized protocols. Patients will receive 16 weeks of treatment with either a SSRI (sertraline or paroxetine) or a SNRI (venlafaxine). The dose range is as follows: sertraline 50-200 mg/day, paroxetine 20-40 mg/day, venlafaxine 75-375 mg/day. Patients unable to continue with the prescribed medication due to side effects and/or lack of response will be prescribed an alternate medication during the first two weeks of the protocol.
Intervention MeSH terms: Antidepressive Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent depression; major depressive disorder; interpersonal therapy; cognitive behavioral therapy; antidepressant therapies; outome predictors; personality dimensions