title: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Cologne, Germany.|Charité University Medicine, St Hedwig-Krankenhaus, Clinic for Psychiatry and Psychotherapy, Berlin, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Henssler
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Cologne, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Kurschus
authors.affiliation: Institute of Medical Statistics, Informatics, and Epidemiology, University of Cologne Medical School, Cologne, Germany.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Franklin
authors.affiliation: Department of Psychiatry, Schlosspark-Hospital, Berlin, Germany.|Department of Psychiatry, Technical University of Dresden Medical School, Dresden, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Bschor
authors.affiliation: Klinik für Psychiatrie und Psychotherapie, Universität zu Köln; Kerpener Straße 62, 50937 Köln, Germany. cbaethge@uni-koeln.de.|Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Cologne, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Baethge
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D000928:Antidepressive Agents