title: 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.
authors.affiliation: 1 Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Huiai Hospital, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: 1 Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Huiai Hospital, Guangzhou, China.
authors.forename: Xin-Hu
authors.initials: XH
authors.lastname: Yang
authors.affiliation: 2 Clinics of Chinese Medicine, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Dong-Bin
authors.initials: DB
authors.lastname: Cai
authors.affiliation: 3 The University of Notre Dame Australia/Marian Centre, Perth, Australia.|4 School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia.
authors.forename: Gabor S
authors.initials: GS
authors.lastname: Ungvari
authors.affiliation: 5 Department of Psychiatry, University of Melbourne, Melbourne, Australia.
authors.forename: Chee H
authors.initials: CH
authors.lastname: Ng
authors.affiliation: 6 Department of General Psychiatry, Institute of Mental Health, Singapore.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: 1 Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Huiai Hospital, Guangzhou, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Ning
authors.affiliation: 7 Unit of Psychiatry, University of Macau, Macau SAR, China.
authors.forename: Yu-Tao
authors.initials: YT
authors.lastname: Xiang
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011388:Prolactin / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D011388:Prolactin; D008687:Metformin
keywords: Prolactin; meta-analysis; metformin; schizophrenia