Long-Term Acute-Phase Treatment With Antidepressants, 8 Weeks and Beyond: A Systematic Review and Meta-Analysis of Randomized, Placebo-Controlled Trials.

Abstract

In clinical practice, acute antidepressant treatment is often applied for several months until remission is achieved. However, data on treatment outcomes beyond 8 weeks are sparse and no systematic review exists to date. This study aims at assessing efficacy and tolerability of antidepressants compared to placebo in acute treatment at and beyond 8 weeks. MEDLINE, Embase, PsycINFO, and CENTRAL databases were systematically searched through March 2014 using generic terms for depressive and affective disorders combined with generic terms for individual drugs and placebo. Double-blind, randomized, placebo-controlled studies of 8 weeks or more comparing antidepressant monotherapy to placebo in adult patients with acute depressive disorder. Data extraction and synthesis followed guidelines of the Cochrane Collaboration. All data were extracted independently by 2 reviewers. Primary outcome was standardized mean difference (SMD) between antidepressant and placebo; secondary outcomes were response, remission, and dropouts. Of 6,043 articles screened, we selected 104 studies that met criteria and included 35,052 patients. Active treatment was statistically significantly superior to placebo, with consistent effect sizes (SMD [95% CL]) after 8, 12, 16, 20, and 24 weeks: 0.27 (0.24, 0.30), 0.34 (0.25, 0.43), 0.24 (0.09, 0.40), 0.31 (0.12, 0.51), and 0.34 (0.18, 0.50), respectively. Results remained stable across secondary outcomes and subgroup and sensitivity analyses. Effect sizes of antidepressant monotherapy compared to placebo seem to be stable over 6 months. These results challenge the assumption that long-term antidepressant effects are due to the natural course of the disorder rather than to a pharmacologic effect.