Aripiprazole,
metformin, and paeoniae-glycyrrhiza decoction (
PGD) have been widely used as adjunctive treatments to reduce
antipsychotic (AP)-induced
hyperprolactinemia in patients with
schizophrenia. However, the comparative efficacy and safety of these medications have not been previously studied. A network meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety between
aripiprazole,
metformin, and
PGD as adjunctive medications in reducing AP-induced
hyperprolactinemia in
schizophrenia. Both international (PubMed, PsycINFO, EMBASE, and Cochrane Library databases) and Chinese (WanFang, Chinese Biomedical, and Chinese National Knowledge infrastructure) databases were searched from their inception until January 3, 2019. Data were analyzed using the Bayesian Markov Chain Monte Carlo simulations with the WinBUGS software. A total of 62 RCTs with 5,550 participants were included in the meta-analysis. Of the nine groups of treatments included, adjunctive
aripiprazole (<5 mg/day) was associated with the most significant reduction in
prolactin levels compared to placebo (posterior MD = -65.52, 95% CI = -104.91, -24.08) and the other eight treatment groups. Moreover, adjunctive
PGD (>1:1) was associated with the lowest rate of all-cause discontinuation compared to placebo (posterior odds ratio = 0.45, 95% CI = 0.10, 3.13) and adjunctive
aripiprazole (>10 mg/day) was associated with fewer total
adverse drug events than placebo (posterior OR = 0.93, 95% CI = 0.65, 1.77) and other eight treatment groups. In addition, when
risperidone,
amisulpride, and
olanzapine were the primary AP medications, adjunctive paeoniae/glycyrrhiza = 1:1,
aripiprazole <5 mg/day, and
aripiprazole >10 mg/day were the most effective treatments in reducing the
prolactin levels, respectively. Adjunctive
aripiprazole,
metformin, and
PGD showed beneficial effects in reducing AP-induced
hyperprolactinemia in
schizophrenia, with
aripiprazole (<5 mg/day) being the most effective one.