Effectiveness of Metformin for Weight Reduction in Children and Adolescents Treated with Mixed Dopamine and Serotonin Receptor Antagonists: A Naturalistic Cohort Study

Objectives: Mixed dopamine and serotonin receptor antagonists (DSRAs) are associated with significant weight gain and its complications. Our aim was to evaluate the effectiveness of metformin in reducing body mass index (BMI) and metabolic parameters in children treated with DSRAs. Methods: We report a naturalistic study of 49 children and adolescents (mean age 14.9 +/- 3.7 years), with BMI >85 percentile for age, treated with DSRAs during 2018-2020 in a child psychiatry clinic. Clinical data, anthropometric measurements, and laboratory tests were compared between those who were (study group, n = 31) and were not (control group, n = 18) treated with metformin. Results: The mean study duration was 9.7 +/- 5.9 months. The BMI standard deviation scores (BMI-SDS) of the study group declined significantly (from 2.08 +/- 0.40 to 1.81 +/- 0.54, p < 0.001), while the BMI-SDS of the control group did not change (from 2.03 +/- 0.45 to 2.04 +/- 0.47, p = 0.838). In the study group, the decline in the delta BMI-SDS/month was more robust among those with good than poor adherence to metformin (-0.047 +/- 0.039 vs. -0.004 +/- 0.017, p = 0.003). The decrease in BMI-SDS was greater for patients treated with risperidone and clothiapine than with other DSRAs. Fasting insulin and insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) declined in the study group (from 25.4 +/- 13.8 to 19.9 +/- 10.7, p = 0.033 and from 5.4 +/- 2.7 to 4.2 +/- 2.1, p = 0.028, respectively). Conclusions: Metformin treatment was associated with significant decreases in BMI, fasting insulin, and HOMA-IR. The effect of metformin seems to be dependent on adherence and type of DSRAs.