Can Metformin Counteract Antipsychotic-Induced Hyperprolactinemia? New Evidence Emerges

The meta-analysis published in the Journal of Psychopharmacology revealed that the reduction was more pronounced with higher doses (1500 mg), shorter treatment durations (<24 weeks), BMI over 25 kg/m², and illness duration exceeding one year compared to controls. Additionally, metformin demonstrated good tolerability, with no significant increase in adverse events or treatment discontinuation, underscoring its potential as an adjunct therapy.

Hyperprolactinemia is a frequent side effect of antipsychotic medications, affecting up to 70% of individuals with schizophrenia. It can lead to complications such as menstrual irregularities, sexual dysfunction, and decreased bone mineral density, increasing the risk of osteoporosis. Given the limited treatment options available, researchers have been investigating the potential of metformin, a commonly used antidiabetic drug, as a therapeutic intervention for managing antipsychotic-induced hyperprolactinemia. Mong-Liang Lu, Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, and colleagues aimed to evaluate its effectiveness in addressing this concern.

For this purpose, the researchers conducted a systematic search across PubMed, CNKI, Embase, Cochrane, and Web of Science up to January 31, 2024, to identify randomized controlled trials (RCTs) assessing the impact of metformin on prolactin levels in patients with schizophrenia. The extracted data were analyzed using a random-effects meta-analysis to synthesize the findings.

Key findings:

• The meta-analysis included 10 randomized controlled trials with 1,046 participants, where 584 received metformin, and 462 were in the control group (placebo or no treatment).
• Metformin significantly lowered prolactin levels compared to the control group, with an average reduction of 34.88 ng/mL.
• Higher doses (1,500 mg), shorter treatment durations (less than 24 weeks), higher BMI (above 25 kg/m²), and longer illness duration (more than one year) were linked to greater reductions in prolactin levels.
• Metformin was well tolerated, with no significant increase in adverse events or treatment discontinuation compared to the control group.

The authors of this meta-analysis highlight the potential of metformin as a therapeutic option for managing antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Their findings suggest that metformin is well tolerated and particularly effective at higher doses and shorter treatment durations in individuals with a higher BMI and those with a longer duration of illness. However, the researchers emphasize the need for cautious interpretation due to the high heterogeneity across studies.

They recommend further investigations to explore demographic and clinical factors that may influence treatment response, ultimately optimizing metformin’s role in managing hyperprolactinemia in this patient population.

Reference:

Goh, K. K., Chen, H., & Lu, L. Evaluating the efficacy of metformin in reducing hyperprolactinemia among patients with schizophrenia: A meta-analysis of randomized controlled trials. Journal of Psychopharmacology. https://doi.org/10.1177/02698811251326945