Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study.
OBJECTIVE
Data on the treatment of antipsychotic-induced amenorrhea, particularly when occurring with weight gain, are limited. The authors investigated the efficacy and safety of metformin in the treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia.


METHODS
Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months. The primary outcome measures were restoration of menstruation and change in body weight and body mass index (BMI). Secondary outcome measures were changes in levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone; in fasting levels of insulin and glucose; in LH/FSH ratio; and in insulin resistance index. Repeated mixed models with repeated-measures regression analyses and binary logistic regression were used in the analysis.


RESULTS
A total of 76 patients completed the 6-month trial. Significantly more patients in the metformin group (N=28, 66.7%) than in placebo group (N=2, 4.8%) resumed their menstruation. Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04. In contrast, patients who received placebo had a mean increase in BMI of 0.85. The prolactin, LH, and testosterone levels and LH/FSH ratio decreased significantly in the metformin group at months 2, 4, and 6, but these levels did not change in the placebo group.


CONCLUSIONS
Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia.
Institute of Mental Health of the Second Xiang ya Hospital, Central South University, Changsha, China. wurenrong2005@yahoo.com.cn
Ren-Rong
RR
Wu
Hua
H
Jin
Keming
K
Gao
Elizabeth W
EW
Twamley
Jian-Jun
JJ
Ou
Ping
P
Shao
Juan
J
Wang
Xiao-Feng
XF
Guo
John M
JM
Davis
Philip K
PK
Chan
Jing-Ping
JP
Zhao
D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced* / Q000188:drug therapy; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D007986:Luteinizing Hormone / Q000097:blood; D008687:Metformin / Q000627:therapeutic use*; D011388:Prolactin / Q000097:blood; D012559:Schizophrenia / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood; D015430:Weight Gain / Q000187:drug effects*; D055815:Young Adult
D014150:Antipsychotic Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013739:Testosterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D008687:Metformin