title: Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis.
abstract: OBJECTIVE
  To examine the efficacy and overall tolerability of augmentation of standard antidepressants with atypical antipsychotic agents for treatment-resistant major depressive disorder.
  
  
  METHODS
  MEDLINE/PubMed, EMBASE, the Cochrane database, and program syllabi from major psychiatric meetings held since 2000 as well as a number of online clinical trial results registries were searched. Makers of atypical anti-psychotic agents who do not maintain an online clinical study results registry were contacted directly.
  
  
  METHODS
  Double-blind, randomized, placebo-controlled clinical trials assessing adjunctive treatment of standard antidepressants with an atypical antipsychotic agent for treatment-resistant major depressive disorder were identified.
  
  
  METHODS
  Data were extracted with the use of a pre-coded form.
  
  
  RESULTS
  Data from 10 clinical trial reports involving a total of 1500 outpatients with treatment-resistant major depressive disorder were identified and combined using a random-effects model. Patients randomized to adjunctive treatment with an atypical antipsychotic agent were more likely to experience remission (risk ratio [RR] = 1.75, p < .0001) or clinical response (RR = 1.35, p = .001) than patients who received adjunctive placebo. Pooled remission and response rates for the 2 treatment groups were 47.4% vs. 22.3% and 57.2% vs. 35.4%, respectively. Although there was no difference in overall discontinuation rates (p = .929) or the rate of discontinuation due to inefficacy (p = .133) between the 2 treatment groups, the rate of discontinuation due to adverse events was lower among placebo-treated patients (RR = 3.38, p < .0001).
  
  
  CONCLUSIONS
  These results support the utility of augmenting standard antidepressants with atypical antipsychotic agents for treatment-resistant major depressive disorder. An obvious limitation of this work is the absence of data focusing on the use of aripiprazole and ziprasidone. Future short- as well as long-term studies comparing the efficacy, safety, and tolerability of this versus other adjunctive strategies are warranted.
authors.affiliation: Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. gpapakostas@partners.org
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.forename: Juliana
authors.initials: J
authors.lastname: Smith
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents