Adjunctive Aripiprazole For The Treatment Of Antipsychotic-induced Hyperprolactinemia : System Review And Meta-analysis Of Randomized Controlled Trials

Background Hyperprolactinemia(HPL) is a common and serious adverse effect caused by antipsychotic medications. Recent years,there are compelling evidence suggest that aripiprazole can reverse antipsychoticinduced HPL.But the results are not consistent, even there is contradictory. Although there have been a related systematic review, to a certain extent, it has some limitations because of only five studies included.Aim To evaluate the safety and efficacy of aripiprazole as an adjunctive treatment for antipsychotic-induced HPL according to the conduction of an updated meta-analysis of all randomized controlled trials(RCTs).Methods We performed a literature search of data for RCTs about the use of aripiprazole in treating antipsychotic-induced HPL published in English and Chinese databases up to January 20, 2015. All the Studies were selected using pre-defined inclusion and exclusion criteria. The Risk of Bias(ROB) tool was used to evaluate risk of biases, the GRADE measure was used to assess the quality of evidence, these were recommended by the Cochrane Collaboration,and Review Manager 5.3 software was used for data analysis.Results(1)21 randomized controlled trials with 1853 individuals met the inclusion criteria in the meta-analysis, 19 of which were conducted in mainland China.(2) Meta-analysis of data from 8 of the studies with 604 individuals found that HPL recovery of adjunctive treatment with aripiprazole were significantly higher than control group(risk ratio [RR]=19.2, 95%CI=11.0-33.5). No significant difference in overall adverse effect was observed between groups with or without aripiprazole.However, somnolence(RR=2.76, 95%CI=1.34-5.69) and headaches(RR=2.31, 95%CI=1.08-4.92) were more frequent in the adjunctive aripiprazole groups. The subgroup analysis indicated that highdose 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.(3)The risk of bias in the studies was rated as ‘high’ in 6 of the studies and ‘unclear’ in 15 of the 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. This meta-analysis demonstrates that adjunctive aripiprazole is both effective and safe as a reasonable choice in the treatment of antipsychotic-induced hyperprolactinemia,although may increase the risk of somnolence and headaches. A degree of prolactin normalization are similar with using different dose aripiprazole..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.