Relapse prevention in schizophrenia with new-generation antipsychotics: a systematic review and exploratory meta-analysis of randomized, controlled trials

Am J Psychiatry. 2003 Jul;160(7):1209-22. doi: 10.1176/appi.ajp.160.7.1209.


Objective: The authors performed a systematic review and meta-analysis of studies of the potential of new-generation antipsychotic drugs to improve adherence and decrease relapse rates in patients with schizophrenia.

Method: Randomized, controlled trials comparing new-generation antipsychotic drugs with placebo and/or conventional antipsychotics were identified. Data on relapse, general treatment failure, and dropout due to adverse events were extracted and combined in a meta-analysis.

Results: Because few trials were available for each individual drug, the effects of new-generation antipsychotic drugs as a group were analyzed. The analysis of six placebo comparisons, involving a total of 983 patients, clearly demonstrated that new-generation antipsychotic drugs are effective for relapse prevention. Eleven studies with a total of 2,032 patients provided comparative data on relapse/treatment failure for new-generation and conventional antipsychotics. The analysis revealed that rates of relapse and overall treatment failure were modestly but significantly lower with the newer drugs. Whether this advantage was partly mediated by improved adherence to treatment remains unclear. No significant superiority in terms of fewer dropouts due to adverse events was found for the newer drugs. Furthermore, a number of methodological problems were identified.

Conclusions: Overall, the currently available data suggest that new-generation antipsychotics have the potential to reduce relapse rates. Methodological issues to be addressed in future trials include the choice of comparator, use of appropriate doses, application of clinically relevant relapse criteria, monitoring of adherence, and minimization of dropouts.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / classification
  • Antipsychotic Agents / therapeutic use*
  • Humans
  • Mathematics
  • Models, Theoretical
  • Odds Ratio
  • Patient Dropouts
  • Randomized Controlled Trials as Topic
  • Research Design / standards
  • Risk
  • Schizophrenia / drug therapy*
  • Schizophrenia / prevention & control
  • Secondary Prevention
  • Treatment Failure
  • Treatment Outcome


  • Antipsychotic Agents