OBJECTIVES: Treatment discontinuation has been increasingly used as a quantifiable tool for measuring the overall effectiveness of antipsychotic medications, including efficacy, safety, and tolerability of a drug. While results have been inconsistent, several studies have found that olanzapine and other second-generation antipsychotics (SGA) are more effective in the treatment of schizophrenia compared to first-generation antipsychotics (FGA). This meta-analysis compared time to and rate of treatment discontinuation of antipsychotics in schizophrenia. METHODS: Electronic search strategies identified all relevant papers on the topic published up to April 2009. Randomized controlled trials (RCTs) and observational studies that compared olanzapine with SGAs and/or FGAs for patients with schizophrenia were included in the meta-analyses. Hazard ratios (HR), Relative Risks (RR) and their associated 95% confidence intervals (CIs) were extracted. RESULTS: There were 60 RCTs (N=33,360) and 27 observational studies (N=202,591) included. The meta-analysis of time to discontinuation revealed that olanzapine was significantly better as compared to aripiprazole, quetiapine, risperidone, ziprasidone, and perphenazine within randomized trials and better than amisulpride, risperidone, haloperidol, and perphenazine within observational studies. Discontinuation rates in the RCTs were significantly lower for olanzapine compared to all antipsychotics except for clozapine. In the observational studies, olanzapine was more effective than amisulpride and haloperidol, and less effective than clozapine. Subgroup analysis indicated that industry sponsorship (Lilly vs. other sources) and olanzapine dosages did not affect the results, except for observational studies published by companies other than Lilly which found olanzapine to be more favorable compared to FGAs). CONCLUSIONS: In both randomized trials and observational studies, time to and rates of discontinuation, which are overall indices of effectiveness, olanzapine was better than most SGAs and FGAs, except for clozapine.