Enhanced adaptive capacities after brief treatment for depression.

Using data from the National Institute of Mental Health-sponsored Treatment of Depression Collaborative Research Program, the authors examined predictors of the intensity of depressive symptoms after the brief treatment of depression. Multilevel modeling was applied to measures of depression and stress assessed at termination and at 6-, 12-, and 18-month follow-ups. The slope of depression on stress was used to index stress reactivity. Patients with high mean levels of stress experienced more intense depressive symptoms, but this effect was moderated by patients' reports of the extent to which they had acquired enhanced adaptive capacities (EACs) in treatment. Patients who reported high EAC early in the follow-up were more resilient in the face of stress than those with low EAC. Greater EACs were found for patients who received psychotherapy than medication or placebo and, across all treatments, for patients with a stronger therapeutic alliance. These findings suggest that treatments should be evaluated in terms of their impact on patients' developing adaptive capacities as well as the reduction of symptomatology.

Relation of therapeutic alliance and perfectionism to outcome in brief outpatient treatment of depression.

Prior analyses of the National Institute of Mental Health Treatment of Depression Collaborative Research Program demonstrated that perfectionism was negatively related to outcome, whereas both the patient's perception of the quality of the therapeutic relationship and the patient contribution to the therapeutic alliance were positively related to outcome across treatment conditions (S. J. Blatt, D. C. Zuroff, D. M. Quinlan, & P. A. Pilkonis, 1996; J. L. Krupnick et al., 1996). New analyses examining the relations among perfectionism, perceived relationship quality, and the therapeutic alliance demonstrated that (a) the patient contribution to the alliance and the perceived quality of the therapeutic relationship were independent predictors of outcome, (b) perfectionistic patients showed smaller increases in the Patient Alliance factor over the course of treatment, and (c) the negative relation between perfectionism and outcome was explained (mediated) by perfectionistic patients' failure to develop stronger therapeutic alliances.

Therapist competence ratings in relation to clinical outcome in cognitive therapy of depression.

This study reports on the relationship of therapist competence to the outcome of cognitive-behavioral treatment in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Outpatients suffering from major depressive disorder were treated by cognitive-behavioral therapists at each of 3 U.S. sites using a format of 20 sessions in 16 weeks. Findings provide some support for the relationship of therapist competence (as measured by the Cognitive Therapy Scale) to reduction of depressive symptomatology when controlling for therapist adherence and facilitative conditions. The results are, however, not as strong or consistent as expected. The component of competence that was most highly related to outcome is a factor that reflects the therapist's ability to structure the treatment.

Pharmacotherapy response and diagnostic validity in atypical depression.

BACKGROUND: The validity of diagnostic criteria and the efficacy of tricyclic antidepressant pharmacotherapy for atypical depression were studied in the NIMH Treatment of Depression Collaborative Research Program. METHODS: Outpatients with major depressive disorder (N = 239) entered a 16-week clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive behavior therapy, and imipramine or placebo with clinical management. Features of atypical depression were rated on the SADS and ISI and clinical outcome was measured on the HRSD and GAS. RESULTS: Atypical features of mood reactivity and at least one reversed vegetative symptom of hypersomnia, hyperphagia or weight gain (25.2% patients) were predictive of pharmacotherapy non-responsiveness with imipramine compared to placebo. The additional features of diurnal mood variation, 'leaden paralysis', and 'rejection sensitivity' did not further distinguish animipramine non-responsive subgroup. Imipramine did show significant effectiveness compared to placebo among non-atypical patients on measures of depressive symptom change. LIMITATIONS: The predictive influence of atypical features was not accounted for on the basis of depression severity. CONCLUSIONS: This study provides evidence for the predictive validity of atypical features of major depressive disorder, including mood reactivity and at least one reversed vegetative symptom of either hypersomnia, hyperphagia, or weight gain, supporting the inclusion of atypical depressive features, with these criteria, in the DSM-IV.

The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

The relationship between therapeutic alliance and treatment outcome was examined for depressed outpatients who received interpersonal psychotherapy, cognitive-behavior therapy, imipramine with clinical management, or placebo with clinical management. Clinical raters scored videotapes of early, middle, and late therapy sessions for 225 cases (619 sessions). Outcome was assessed from patients' and clinical evaluators' perspectives and from depressive symptomatology. Therapeutic alliance was found to have a significant effect on clinical outcome for both psychotherapies and for active and placebo pharmacotherapy. Ratings of patient contribution to the alliance were significantly related to treatment outcome; ratings of therapist contribution to the alliance and outcome were not significantly linked. These results indicate that the therapeutic alliance is a common factor with significant influence on outcome.

Initial severity and differential treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

Random regression models (RRMs) were used to investigate the role of initial severity in the outcome of 4 treatments (cognitive-behavior therapy [CBT], interpersonal psychotherapy [IPT], imipramine plus clinical management [IMI-CM], and placebo plus clinical management [PLA-CM]) for outpatients with major depressive disorder seen in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Initial severity of depression and impairment of functioning significantly predicted differential treatment effects. A larger number of differences than previously reported were found among the active treatments for the more severely ill patients; this was due, in large part, to the greater power of the present statistical analyses.

Managed care and the role and training of psychiatrists.

While each sector of medical practice and academic medicine confronts the reality of a changing economic environment driven by managed care, psychiatry faces some of the most difficult challenges in defining the future roles and training of psychiatrists. In this paper we describe the challenges and opportunities for psychiatry in this new era, as well as some of the unique problems facing academic psychiatry departments as they seek to fund their academic mission.

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.

Some conceptual and statistical issues in analysis of longitudinal psychiatric data. Application to the NIMH treatment of Depression Collaborative Research Program dataset.

Longitudinal studies have a prominent role in psychiatric research; however, statistical methods for analyzing these data are rarely commensurate with the effort involved in their acquisition. Frequently the majority of data are discarded and a simple end-point analysis is performed. In other cases, so called repeated-measures analysis of variance procedures are used with little regard to their restrictive and often unrealistic assumptions and the effect of missing data on the statistical properties of their estimates. We explored the unique features of longitudinal psychiatric data from both statistical and conceptual perspectives. We used a family of statistical models termed random regression models that provide a more realistic approach to analysis of longitudinal psychiatric data. Random regression models provide solutions to commonly observed problems of missing data, serial correlation, time-varying covariates, and irregular measurement occasions, and they accommodate systematic person-specific deviations from the average time trend. Properties of these models were compared with traditional approaches at a conceptual level. The approach was then illustrated in a new analysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program dataset, which investigated two forms of psychotherapy, pharmacotherapy with clinical management, and a placebo with clinical management control. Results indicated that both person-specific effects and serial correlation play major roles in the longitudinal psychiatric response process. Ignoring either of these effects produces misleading estimates of uncertainty that form the basis of statistical tests of hypotheses.

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.

Personality disorders and treatment outcome in the NIMH Treatment of Depression Collaborative Research Program.

The authors investigated the relationship between personality disorders and treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program, which involved 239 outpatients with major depressive disorder randomly assigned to one of four 16-week treatment conditions. Patients with personality disorders (74% of the sample) had a significantly worse outcome in social functioning than patients without personality disorders and were significantly more likely to have residual symptoms of depression. There were no significant differences in work functioning or in mean depression scores at treatment termination. Outcome was similar for patients in the different clusters of personality disorders.

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.

Conceptual and methodological issues in comparative studies of psychotherapy and pharmacotherapy, II: Nature and timing of treatment effects.

This is the second of two articles on the conceptual and methodological problems involved in comparing the effectiveness of drugs and psychotherapy in the treatment of mental disorders. Part II focuses on differences between psychotherapy and pharmacotherapy in the nature of treatment effects and related goals for treatment, differences in the time course of treatment effects, and potential sources of bias in the research setting. In designing comparative studies of psychotherapy and pharmacotherapy, investigators should address methodological choices explicitly and consider the implications for interpretation of findings.

Conceptual and methodological issues in comparative studies of psychotherapy and pharmacotherapy, I: Active ingredients and mechanisms of change.

There has recently been an increased focus on comparing the effectiveness of drugs and psychotherapy in the treatment of mental disorders. The marked differences between these two treatment forms raise many conceptual and methodological problems for the investigator. In a two-part series, the authors discuss a number of these conceptual issues and their implications for research design, implementation, and interpretation of findings. Part I focuses on differences in the active ingredients and hypothesized mechanisms of change of psychotherapy and pharmacotherapy. Issues addressed include the need for standardization of treatments, adequate delivery of treatments, and controlling for factors other than the active ingredients of each treatment.

Adrenocortical function and plasma norepinephrine in normal human subjects.

Abnormal adrenocortical regulation has been reported in patients with endogenous depression, including excessive cortisol production with loss of circadian periodicity and decreased suppression by dexamethasone. The inhibitory effect of the neurotransmitter norepinephrine (NE) on the hypothalamic-pituitary adrenal (HPA) axis through the regulation of corticotropin-releasing factor has been suggested by animal in vitro studies. In this study of six normal human subjects we have examined the relationship of basal cortisol activity and its sensitivity to dexamethasone suppression, measured by 24-hr urinary free cortisol, with basal noradrenergic activity, diurnal variation, and response to postural stimulation, measured by plasma NE. Base-line cortisol and the degree of dexamethasone suppression were significantly inversely correlated with all base-line measures of NE response to stimulation. NE response to stimulation on the morning after dexamethasone was also inversely correlated with the degree of cortisol suppression. The increase in the morning NE response to stimulation after dexamethasone was inversely correlated with both base-line and suppressed cortisol levels. There is significant diurnal variation in stimulated NE activity after dexamethasone. There results are consistent with an inhibitory role for NE in the regulation of HPA system and a reciprocal effect for cortisol on noradrenergic activity. The implication of this relationship for the understanding of adrenocortical regulation in depression is discussed.