Meta-analysis on the efficacy and tolerability of the augmentation of antidepressants with atypical antipsychotics in patients with major depressive disorder

Braz J Med Biol Res. 2014 Jul;47(7):605-16. doi: 10.1590/1414-431x20143672. Epub 2014 Jun 13.


We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / adverse effects
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / adverse effects*
  • Aripiprazole
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / adverse effects
  • Chemotherapy, Adjuvant
  • Depressive Disorder, Major / drug therapy*
  • Dibenzothiazepines / administration & dosage
  • Dibenzothiazepines / adverse effects
  • Double-Blind Method
  • Drug Synergism
  • Humans
  • Middle Aged
  • Olanzapine
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Quetiapine Fumarate
  • Quinolones / administration & dosage
  • Quinolones / adverse effects
  • Randomized Controlled Trials as Topic
  • Remission Induction
  • Risperidone / administration & dosage
  • Risperidone / adverse effects
  • Treatment Outcome
  • Young Adult


  • Antidepressive Agents
  • Antipsychotic Agents
  • Dibenzothiazepines
  • Piperazines
  • Quinolones
  • Benzodiazepines
  • Quetiapine Fumarate
  • Aripiprazole
  • Risperidone
  • Olanzapine