Sona Dimidjian

Antidepressant Drug effects and Depression Severity: A Patient-Level Meta-Analysis

CONTEXT Antidepressant medications represent the best established treatment for major depressive disorder, but there is little evidence that they have a specific pharmacological effect relative to pill placebo for patients with less severe depression. OBJECTIVE To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. DATA SOURCES PubMed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. STUDY SELECTION Randomized placebo-controlled trials of antidepressants approved by the Food and Drug Administration in the treatment of major or minor depressive disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, they included a medication vs placebo comparison for at least 6 weeks, they did not exclude patients on the basis of a placebo washout period, and they used the Hamilton Depression Rating Scale (HDRS). Data from 6 studies (718 patients) were included. DATA EXTRACTION Individual patient-level data were obtained from study authors. RESULTS Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with HDRS scores below 23, Cohen d effect sizes for the difference between medication and placebo were estimated to be less than 0.20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline depression severity and crossed the threshold defined by the National Institute for Clinical Excellence for a clinically significant difference at a baseline HDRS score of 25. CONCLUSIONS The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression

Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have suggested that behavioral components may account for the efficacy of cognitive therapy. The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a randomized placebo-controlled design in adults with major depressive disorder (N = 241). In addition, it examined the importance of initial severity as a moderator of treatment outcome. Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy. The implications of these findings for the evaluation of current treatment guidelines and dissemination are discussed.

Randomized Trial of Behavioral Activation, Cognitive Therapy, and Antidepressant Medication in the Prevention of Relapse and Recurrence in Major Depression

This study followed treatment responders from a randomized controlled trial of adults with major depression. Patients treated with medication but withdrawn onto pill-placebo had more relapse through 1 year of follow-up compared to patients who received prior behavioral activation, prior cognitive therapy, or continued medication. Prior psychotherapy was also superior to medication withdrawal in the prevention of recurrence across the 2nd year of follow-up. Specific comparisons indicated that patients previously exposed to cognitive therapy were significantly less likely to relapse following treatment termination than patients withdrawn from medication, and patients previously exposed to behavioral activation did almost as well relative to patients withdrawn from medication, although the difference was not significantly different. Differences between behavioral activation and cognitive therapy were small in magnitude and not significantly different across the full 2-year follow-up, and each therapy was at least as efficacious as the continuation of medication. These findings suggest that behavioral activation may be nearly as enduring as cognitive therapy and that both psychotherapies are less expensive and longer lasting alternatives to medication in the treatment of depression.

The Origins and Current Status of Behavioral Activation Treatments for Depression

The past decade has witnessed a resurgence of interest in behavioral interventions for depression. This contemporary work is grounded in the work of Lewinsohn and colleagues, which laid a foundation for future clinical practice and science. This review thus summarizes the origins of a behavioral model of depression and the behavioral activation (BA) approach to the treatment and prevention of depression. We highlight the formative initial work by Lewinsohn and colleagues, the evolution of this work, and related contemporary research initiatives, such as that led by Jacobson and colleagues. We examine the diverse ways in which BA has been investigated over time and its emerging application to a broad range of populations and problems. We close with reflections on important directions for future inquiry.

Treatment preference, engagement, and clinical improvement in pharmacotherapy versus psychotherapy for depression.

Pharmacotherapy and psychotherapy are generally effective treatments for major depressive disorder (MDD); however, research suggests that patient preferences may influence outcomes. We examined the effects of treatment preference on attrition, therapeutic alliance, and change in depressive severity in a longitudinal randomized clinical trial comparing pharmacotherapy and psychotherapy. Prior to randomization, 106 individuals with MDD reported whether they preferred psychotherapy, antidepressant medication, or had no preference. A mismatch between preferred and actual treatment was associated with greater likelihood of attrition, fewer expected visits attended, and a less positive working alliance at session 2. There was a significant indirect effect of preference match on depression outcomes, primarily via effects of attendance. These findings highlight the importance of addressing patient preferences, particularly in regard to patient engagement, in the treatment of MDD.

How Would We Know If Psychotherapy Were Harmful

Patients can be harmed by treatment or by the decisions that are made about those treatments. Although dramatic examples of harmful effects of psychotherapy have been reported, the full scope of the problem remains unclear. The field currently lacks consensus about how to detect harm and what to do about it when it occurs. In this article, we define the ways in which treatment (or the inferences about treatment) can do harm and discuss factors that complicate efforts to detect harm. We also recommend methods to detect and understand harm when it occurs, drawing from and modifying many of the same strategies that are used to detect benefit. Specifically, we highlight the value of establishing independent systems for monitoring untoward events in clinical practice, reporting descriptive case studies and qualitative research, and making use of information from randomized clinical trials, including examining potential active ingredients, mechanisms, moderators, and a broad range of outcomes measured over time. We also highlight the value of promoting discussion in the field about standards for defining and identifying harm.

Extreme nonresponse in cognitive therapy: can behavioral activation succeed where cognitive therapy fails?

In a recent placebo-controlled comparison, behavioral activation was superior to cognitive therapy in the treatment of moderate to severely depressed adults. Moreover, a subset of patients exhibited a pattern of extreme nonresponse to cognitive therapy on self-reports of depression not evident on the clinician ratings. These patients were severely depressed, functionally impaired, and had primary support group problems; most also described themselves as having life-long depressions. Comparable numbers of patients with such characteristics were assigned to behavioral activation, indicating that randomization did not fail, and most instances occurred in the context of adequate cognitive therapy. If this pattern of self-reported extreme nonresponse to cognitive therapy replicates, it would suggest that there might be a subset of patients who see themselves as doing better with sustained attention to behavior change in time-limited treatment.

Two Aspects of the Therapeutic Alliance: Differential Relations With Depressive Symptom Change

OBJECTIVE The therapeutic alliance has been linked to symptom change in numerous investigations. Although the alliance is commonly conceptualized as a multidimensional construct, few studies have examined its components separately. The current study explored which components of the alliance are most highly associated with depressive symptom change in cognitive therapy (CT). METHOD Data were drawn from 2 published randomized, controlled clinical trials of CT for major depressive disorder (n = 105, mean age = 40 years, female = 62%, White = 82%). We examined the relations of 2 factor-analytically derived components of the Working Alliance Inventory (WAI; Horvath & Greenberg, 1986, 1989) with symptom change on the Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) that occurred either prior to or subsequent to the examined sessions. WAI ratings were obtained at an early and a late session for each therapist-patient dyad. RESULTS Variation in symptom change subsequent to the early session was significantly related to the WAI factor that assesses therapist-patient agreement on the goals and tasks of therapy but not to a factor assessing the affective bond between therapist and patient. In contrast, both factors, when assessed in a late session, were significantly predicted by prior symptom change. CONCLUSIONS These findings may reflect the importance, in CT, of therapist-patient agreement on the goals and tasks of therapy. In contrast, the bond between therapist and patient may be more of a consequence than a cause of symptom change in CT. The implications of these results and directions for future research are discussed.

Nonpharmacologic Intervention and Prevention Strategies for Depression During Pregnancy and the Postpartum

Perinatal depression is a serious and disabling disorder that has enduring consequences for both women and their children. Although efficacious pharmacologic strategies are available, many perinatal women are reluctant to continue or start antidepressant medications because of the concern about impact on the fetus or, later, the nursing infant. Weighing the costs and benefits of pharmacologic strategies often requires complex-decision making on the part of obstetric providers and patients. Nonpharmacologic intervention and prevention strategies offer the potential of beneficial outcomes without substantial risk profiles. This paper reviews the evidence base for nonpharmacologic intervention and prevention strategies for depression during pregnancy and the postpartum. The evidence base suggests that efficacious nonpharmacologic options are available for women during pregnancy and postpartum; however, important research questions remain.

Prospects for a clinical science of mindfulness-based intervention.

Mindfulness-based interventions (MBIs) are at a pivotal point in their future development. Spurred on by an ever-increasing number of studies and breadth of clinical application, the value of such approaches may appear self-evident. We contend, however, that the public health impact of MBIs can be enhanced significantly by situating this work in a broader framework of clinical psychological science. Utilizing the National Institutes of Health stage model (Onken, Carroll, Shoham, Cuthbert, & Riddle, 2014), we map the evidence base for mindfulness-based cognitive therapy and mindfulness-based stress reduction as exemplars of MBIs. From this perspective, we suggest that important gaps in the current evidence base become apparent and, furthermore, that generating more of the same types of studies without addressing such gaps will limit the relevance and reach of these interventions. We offer a set of 7 recommendations that promote an integrated approach to core research questions, enhanced methodological quality of individual studies, and increased logical links among stages of clinical translation in order to increase the potential of MBIs to impact positively the mental health needs of individuals and communities.