Temporal course of change of depression.

Two hundred fifty moderately to severely depressed outpatients were randomly assigned to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, imipramine plus clinical management (IMI-CM), or pill placebo plus clinical management. Two hundred thirty-nine patients actually began treatment. The most rapid change in depressive symptoms occurred in the IMI-CM condition, which achieved significantly better results than the other treatments at 8 and 12 weeks on 1 or more variables. Change over the course of treatment on variables hypothesized to be most specifically affected by the respective treatments was found only in the case of pharmacotherapy, in which imipramine produced significantly greater changes on the endogenous measure at 8 and 12 weeks.

Course of depressive symptoms over follow-up. Findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

We studied the course of depressive symptoms during an 18-month naturalistic follow-up period for outpatients with Major Depressive Disorder treated in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. The treatment phase consisted of 16 weeks of randomly assigned treatment with the following: cognitive behavior therapy, interpersonal therapy, imipramine hydrochloride plus clinical management (CM), or placebo plus CM. Follow-up assessments were conducted at 6, 12, and 18 months after treatment. Of all patients entering treatment and having follow-up data, the percent who recovered (8 weeks of minimal or no symptoms following the end of treatment) and remained well during follow-up (no Major Depressive Disorder relapse) did not differ significantly among the four treatments: 30% (14/46) for those in the cognitive behavior therapy group, 26% (14/53) for those in the interpersonal therapy group, 19% (9/48) for those in the imipramine plus CM group, and 20% (10/51) for those in the placebo plus CM group. Among patients who had recovered, rates of Major Depressive Disorder relapse were 36% (8/22) for those in the cognitive behavior therapy group, 33% (7/21) for those in the interpersonal therapy group, 50% (9/18) for those in the imipramine plus CM group, and 33% (5/15) for those in the placebo plus CM group. The major finding of this study is that 16 weeks of these specific forms of treatment is insufficient for most patients to achieve full recovery and lasting remission. Future research should be directed at improving success rates of initial and maintenance treatments for depression.

Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program.

OBJECTIVE: The authors investigated patient characteristics predictive of treatment response in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program. METHOD: Two hundred thirty-nine outpatients with major depressive disorder according to the Research Diagnostic Criteria entered a 16-week multicenter clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive-behavior therapy, imipramine with clinical management, or placebo with clinical management. Pretreatment sociodemographic features, diagnosis, course of illness, function, personality, and symptoms were studied to identify patient predictors of depression severity (measured with the Hamilton Rating Scale for Depression) and complete response (measured with the Hamilton scale and the Beck Depression Inventory). RESULTS: One hundred sixty-two patients completed the entire 16-week trial. Six patient characteristics, in addition to depression severity previously reported, predicted outcome across all treatments: social dysfunction, cognitive dysfunction, expectation of improvement, endogenous depression, double depression, and duration of current episode. Significant patient predictors of differential treatment outcome were identified. 1) Low social dysfunction predicted superior response to interpersonal psychotherapy. 2) Low cognitive dysfunction predicted superior response to cognitive-behavior therapy and to imipramine. 3) High work dysfunction predicted superior response to imipramine. 4) High depression severity and impairment of function predicted superior response to imipramine and to interpersonal psychotherapy. CONCLUSIONS: The results demonstrate the relevance of patient characteristics, including social, cognitive, and work function, for prediction of the outcome of major depressive disorder. They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities, which may be of value in the selection of patients for alternative treatments.

Mode-specific effects among three treatments for depression.

In the NIMH Treatment of Depression Collaborative Research Program (TDCRP), 250 depressed outpatients were randomly assigned to interpersonal psychotherapy, cognitive-behavioral therapy, imipramine plus clinical management, or pill placebo plus clinical management treatments. Although all treatments demonstrated significant symptom reduction with few differences in general outcomes, an important question concerned possible effects specific to each treatment. The therapies differ in rationale and procedures, suggesting that mode-specific effects may differ among treatments, each of which was precisely specified, applied appropriately, and shown to be discriminable. Outcome measures were selected for presumed sensitivity to the different treatments. Findings provided only scattered and relatively insubstantial support for mode-specific differences. None of the therapies produced consistent effects on measures related to its theoretical origins.

National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments.

We investigated the effectiveness of two brief psychotherapies, interpersonal psychotherapy and cognitive behavior therapy, for the treatment of outpatients with major depression disorder diagnosed by Research Diagnostic Criteria. Two hundred fifty patients were randomly assigned to one of four 16-week treatment conditions: interpersonal psychotherapy, cognitive behavior therapy, imipramine hydrochloride plus clinical management (as a standard reference treatment), and placebo plus clinical management. Patients in all treatments showed significant reduction in depressive symptoms and improvement in functioning over the course of treatment. There was a consistent ordering of treatments at termination, with imipramine plus clinical management generally doing best, placebo plus clinical management worst, and the two psychotherapies in between but generally closer to imipramine plus clinical management. In analyses carried out on the total samples without regard to initial severity of illness (the primary analyses), there was no evidence of greater effectiveness of one of the psychotherapies as compared with the other and no evidence that either of the psychotherapies was significantly less effective than the standard reference treatment, imipramine plus clinical management. Comparing each of the psychotherapies with the placebo plus clinical management condition, there was limited evidence of the specific effectiveness of interpersonal psychotherapy and none for cognitive behavior therapy. Superior recovery rates were found for both interpersonal psychotherapy and imipramine plus clinical management, as compared with placebo plus clinical management. On mean scores, however, there were few significant differences in effectiveness among the four treatments in the primary analyses. Secondary analyses, in which patients were dichotomized on initial level of severity of depressive symptoms and impairment of functioning, helped to explain the relative lack of significant findings in the primary analyses. Significant differences among treatments were present only for the subgroup of patients who were more severely depressed and functionally impaired; here, there was some evidence of the effectiveness of interpersonal psychotherapy with these patients and strong evidence of the effectiveness of imipramine plus clinical management. In contrast, there were no significant differences among treatments, including placebo plus clinical management, for the less severely depressed and functionally impaired patients.