Using aripiprazole to reduce antipsychotic-induced hyperprolactinemia: meta-analysis of currently available randomized controlled trials

BACKGROUND Hyperprolactinemia (HPL) is a common side effect of antipsychotic medications. Recent reports suggest that aripiprazole can ameliorate antipsychotic-induced HPL, but results are inconsistent and the single available systematic review only considered five studies. AIM Conduct an updated meta-analysis of all randomized controlled trials (RCTs) about the efficacy and safety of aripiprazole as an adjunctive treatment for antipsychotic-induced hyperprolactinemia. METHODS English and Chinese databases were searched for RCTs about the use of aripiprazole in treating antipsychotic-induced HPL published by January 20, 2015. Studies were selected using pre-defined inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate risk of biases, the Cochrane GRADE measure was used to assess the quality of evidence, and Review Manager 5.3 software was used for data analysis. RESULTS A total of 21 studies, 19 of which were conducted in mainland China, were included in the analysis. Meta-analysis of data from 8 of the studies with a pooled sample of 604 individuals found that compared to the control condition adjunctive aripiprazole significantly increased the proportion of participants who experienced HPL recovery (risk ratio [RR]=19.2, 95%CI=11.0-33.5). The proportion who experienced any adverse effect during follow-up did not differ between the two groups, but the aripiprazole group was more likely to report somnolence (RR=2.76, 95%CI=1.34-5.69) and headaches (RR=2.31, 95%CI=1.08-4.92). High-dose aripiprazole (>5mg/day) was more effective than low-dose (<5mg/day) aripiprazole (RR=30.0, 95%CI=10.2-120.7 v. RR=15.1, 95%CI=8.1-28.1), but this difference was not statistically significant. The risk of bias in the studies was rated as 'high' in 6 of the studies and 'unclear' in 15 studies, and the quality of evidence was rated as 'high' for only 7 of the 57 outcome measures assessed. CONCLUSIONS This study systematically reviewed and evaluated all relevant RCTs and found that adjunctive aripiprazole is effective and safe to use in the treatment of antipsychotic-induced HPL. However, the low quality of some of the studies, the incomplete methodological information provided for most of the studies, and the relatively short follow-up time of the studies raises question about the validity of the results. Further work that resolves these methodological and reporting issues is needed.