Prolactin levels influenced by antipsychotic drugs in schizophrenia: A systematic review and network meta-analysis

Prolactin increase is a common side effect in antipsychotic treatment of schizophrenia, which crucially impacts drug choice and treatment compliance. As previous reviews by our group on this topic have included only few Chinese studies, we aimed to compare and rank antipsychotics based on broader evidence. This systematic review pooled data of 92 included studies from previous systematic review by Huhn et al. and 38 newly-added studies from Chinese-database search, including Chinese databases of China National Knowledge Infrastructure (CNKI), WANFANG DATA, WEIPU Journal Net (VIP) and Sino Biomedicine Service System (SinoMed) up to 20 May 2020. We conducted both network meta-analysis (NMA) and pairwise meta-analysis. The primary outcome was prolactin increase (continuous data). We calculated mean differences (MDs) for prolactin level with 95% confidence intervals (CIs) using random-effects model as primary analysis. 130 RCTs with 25,610 participants were included. Newer antipsychotics (risperidone, amisulpride and paliperidone) and older antipsychotics (chlorpromazine, haloperidol and sulpride) increase prolactin levels with large effect sizes. The SMD results were not identical to the MD results because consistency and heterogeneity assumption was tested to be different in calculations. Sensitivity analyses removing two studies with massive baseline imbalance or removing Chinese studies with high risk of bias did not affect the result. In contrast to a previous review clozapine and zotepine were no longer associated with decreased prolactin levels compared to placebo. Risperidone's ranking has more implications supported by CINeMA. This NMA draws the conclusion with larger sample size and extends evidence to more literature in this field.