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Adjunctive metformin for antipsychotic-related hyperprolactinemia: A meta-analysis of randomized controlled trials.

Abstract
Hyperprolactinemia is a common and severe antipsychotic-induced adverse drug reaction. This meta-analysis of randomized controlled trials systematically examined the efficacy and safety of adjunctive metformin for antipsychotic-related hyperprolactinemia in schizophrenia patients. Two independent investigators searched, extracted, and synthesized data. Weighted mean differences and risk ratios with their 95% confidence intervals were calculated using random effect model. Four randomized controlled trials ( n=509) comparing adjunctive metformin ( n=253) with the control groups ( n=256), lasting 22.7 weeks of treatment, were included in the meta-analysis. The metformin group had significantly lower serum prolactin level at endpoint (four randomized controlled trials, n=501; weighted mean difference: -6.87 ug/L (95% confidence interval: -13.24 to -0.51), p=0.03; I2=80%) with "moderate quality" based on the grading of recommendations assessment, development, and evaluation system. In patients with menstrual disturbances, the rate of menstruation resumption was 66.7% in the metformin group and 4.8% in the control group. Adverse drug reactions and all-cause discontinuation (three randomized controlled trials, n=339, risk ratio: 0.76 (95% confidence interval: 0.29, 1.97), p=0.57; I2= 0%) were similar between the two groups. Adjunctive metformin appears to be effective and safe for reducing antipsychotic-induced hyperprolactinemia and prolactin-related symptoms in schizophrenia patients. Higher quality randomized controlled trials with a large sample size are warranted to confirm these findings.
AuthorsWei Zheng, Xin-Hu Yang, Dong-Bin Cai, Gabor S Ungvari, Chee H Ng, Nan Wang, Yu-Ping Ning, Yu-Tao Xiang
JournalJournal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 31 Issue 5 Pg. 625-631 (05 2017) ISSN: 1461-7285 [Electronic] United States
PMID28372526 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
Chemical References
  • Antipsychotic Agents
  • Prolactin
  • Metformin
Topics
  • Adolescent
  • Adult
  • Antipsychotic Agents (adverse effects)
  • Female
  • Humans
  • Hyperprolactinemia (chemically induced, drug therapy)
  • Male
  • Metformin (therapeutic use)
  • Middle Aged
  • Prolactin (therapeutic use)
  • Randomized Controlled Trials as Topic
  • Schizophrenia (drug therapy)
  • Young Adult

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