Dose-Dependent Efficacy of Aripiprazole in Treating Patients With Schizophrenia or Schizoaffective Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Purpose: To compare the efficacy and tolerability of different administration strategies of aripiprazole.

Methods

We searched MEDLINE, EMBASE, the Cochrane Central, Web of Science, China National Knowledge Infrastructure(CNKI), and Wanfang Data Knowledge Service Platform(Wanfang) for randomized controlled trials (RCTs) of aripiprazole, using the terms: (aripiprazole) AND (schizophr* OR schizoaff*) AND ("syndrome scale" OR PANSS) AND (clini* OR trial). We retrieved study design, participant characteristics, comparison groups, and outcomes from each study.

Results

In total, nine RCTs were selected for meta-analysis, which covered ~1,187 participants. We defined two treatment groups that represent different treatment strategies: (1) the high-dose group (the high-dose strategy) rapidly increased to doses higher than 15 mg/day in 2 weeks or began with doses higher than 15 mg/day, otherwise the group was defined as (2) the low-dose group (the low-dose strategy). If the initial or target doses of aripiprazole in a study were all higher than 15 mg/day, the high- and low-dose groups were created based on the relative level of the dose. The high-dose group showed significantly greater reductions in Positive and Negative Syndrome Scale (PANSS) total scores (standardized mean differences = -8.31, 95% confidence interval [CI] = -16.48, -0.13; P < 0.01; I 2 = 96%) than the low-dose group. The high-dose group showed superior effects compared with the low-dose group in long-term studies (more than 8 weeks) (standardized mean differences = -13.81, 95% CI = -25.07, -2.55; P < 0.01; I 2 = 96%). With exception of somnolence, we did not find significant differences in side effects or discontinuation due to adverse events. Sensitivity analyses produced similar results.

Conclusion

The high-dose treatment strategy of aripiprazole for patients with schizophrenia or schizoaffective disorder may bring more benefits without obvious side effects.