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Am J Psychiatry. 2012 Aug 1;169(8):813-21
Authors: Wu RR, Jin H, Gao K, Twamley EW, Ou JJ, Shao P, Wang J, Guo XF, Davis JM, Chan PK, Zhao JP
Abstract
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.
METHOD: 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.
PMID: 22711171
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Note the limit of studying only first-episode schizophrenia. This group is the easiest to treat and generally has the best response to antipsychotics – up to 20% reduction in severity of symptoms.
Metformin generally may work so long as there is insulin resistance and blood sugar elevation. However, if blood sugar is low even in the presence of insulin resistance, weight gain may occur instead as appetite may be promoted by Metformin.
Metformin may also cause a mismatch between the brain’s need for glucose and the liver’s ability to supply it – resulting in impaired cognition in some patients – particularly when there is little insulin resistance present. The best target patients are those who already have significant insulin resistance or diabetes.
In real-life patients, weight loss generally doesn’t occur with Metformin, particularly if appetite is strongly increased by antipsychotic treatment and mental illness limits excercise, and caloric reduction is not maintained. Metformin doesn’t work in a vacuum. Eventually, caloric reduction needs to be done to lose weight.