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Metformin effective for weight gain associated with atypical antipsychotic use in children

Metformin significantly improved BMI and weight outcomes among children and adolescents who experienced weight gain associated with atypical antipsychotic use for autism spectrum disorders.

“The atypical antipsychotic medications risperidone and aripiprazole are the only treatments approved by the FDA for use in autism spectrum disorder (ASD). Both medications improve irritability and agitation symptoms in children with ASD as young as 5 (risperidone) or 6 (aripiprazole) years. Unfortunately, these medications also cause weight gain, and greater cumulative exposure is also associated with increased diabetes risk,” Evdokia Anagnostou, MD, of Holland Bloorview Kids Rehabilitation Hospital, Toronto, and colleagues wrote. “Although weight gain may be reversible, stopping these medicines often leads to relapse of irritability and agitation.”

To assess efficacy of metformin for weight gain associated with atypical antipsychotic use for ASD, researchers conducted a 16-week, double-blind, placebo-controlled randomized clinical trial at four centers in the U.S. and Canada. Study participants (n = 60) received metformin or placebo up to 500 mg twice daily among children aged 6 to 9 years or 850 mg twice daily among those aged 10 to 17 years. The cohort had a mean age of 12.8 years.

From baseline to week 16, metformin significantly reduced BMI z scores (P = .003), compared with placebo.

Secondary body composition measures, including raw BMI (–0.95; 95% CI, –1.46 to –0.45) and raw weight (–2.73; 95% CI, –4.04 to –1.43) also statistically significantly improved in the metformin group.

Metabolic variables did not statistically significantly improve.

Metformin was well-tolerated overall.

Gastrointestinal adverse events were more common in the metformin group (25.1% vs. 6.8%; P = .005), compared with placebo.

“Metformin was significantly more efficacious than the placebo for decreasing weight gain associated with the use of atypical antipsychotics in this population. The primary disadvantage for the active treatment group was a significantly higher percentage of treatment days with associated gastrointestinal adverse events during the 16 weeks of the trial,” Christopher J. McDougle, MD, of Massachusetts General Hospital, Harvard Medical School, Lexington, Massachusetts, wrote in an accompanying editorial. “Anagnostou et al have made a significant contribution to the literature and provided clinicians with an effective approach to consider for managing weight gain in youths with ASD treated with atypical antipsychotics. In addition to more studies of this approach, alternative strategies that warrant investigation include the coadministration of topiramate, monotherapy with ziprasidone, and undoubtedly others.” – by Amanda Oldt

Disclosure: Anagnostou reports receiving consultation fees and serving on advisory boards for Roche; industry funding from SynapDx and Aventis; royalties from APPI, Springer International Publishing; and other funding from Canadian Institutes of Health Research, Ontario Brain Institute, Department of Defense, Autism Speaks, National Centers of Excellence, and Physician Services Incorporated. McDougle reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.