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 ExtractionIndividual patient-level data were obtained from study authors. ResultsMedication 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. ConclusionsThe 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.

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.

Behavioral activation (BA), as a stand‐alone treatment for depression, began as a behavior therapy treatment condition in a component analysis study of the Beck, Rush, Shaw, and Emery version of cognitive therapy. BA attempts to help depressed people reengage in their lives through focused activation strategies. These strategies counter patterns of avoidance, withdrawal, and inactivity that may exacerbate depressive episodes by generating additional secondary problems in individuals' lives. BA is designed to help individuals approach and access sources of positive reinforcement in their lives, which can serve a natural antidepressant function. Our purpose in this article is to describe BA and the history of its development.

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.

SummaryBackgroundAlthough structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings.MethodsIn this randomised controlled trial, we recruited participants aged 18–65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997.FindingsBetween Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group). Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19·99 [SD 15·70] vs 27·52 [13·26] in EUC alone group; adjusted mean difference −7·57 [95% CI −10·27 to −4·86]; p<0·0001) and higher remission (147 [64%] of 230 had a PHQ-9 score of <10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1·61 [1·34–1·93]) than did those in the EUC alone group. EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference −2·73 [–4·39 to −1·06]; p=0·001), days out of work (−2·29 [–3·84 to −0·73]; p=0·004), intimate partner physical violence in women (0·53 [0·29–0·96]; p=0·04), behavioural activation (2·17 [1·34–3·00]; p<0·0001), and suicidal thoughts or attempts (0·61 [0·45–0·83]; p=0·001). The incremental cost per quality-adjusted life-year gained was $933...