Review of: Anagnostou E, Aman MG, Handen BL, et al. JAMA Psychiatry 2016;73:928–937.

STUDY TYPE: Double-blind, placebo-controlled, randomized clinical trial

Atypical antipsychotics are commonly used to reduce irritability and agitation in children with autism spectrum disorder (ASD). Although effective, these medications lead to weight gain and other metabolic problems. Strategies like tailored diet plans and exercise can help, but they are often not enough. If not interrupted early, for many, continued weight gain will lead to diabetes, hypertension, and heart disease later in life.

A promising approach for managing antipsychotic-associated weight gain is metformin. Through its ability to suppress glucose production in the liver, metformin stabilizes blood sugar levels, reduces ­hunger, and promotes fat loss. Previous studies with adults reveal that metformin can indeed stop or reverse weight gain associated with the use of atypical antipsychotics. Similar data exist for children as well, but we know little with respect to those with ASD. To explore this issue, researchers randomized 61 children with ASD between the ages of 6 and 17 to receive metformin (n = 29) or placebo (n = 32). Nearly all were on either risperidone (60%) or aripiprazole (38%). The children were tracked for 16 weeks for changes in body mass index (BMI) and adverse events. For kids between 6 and 9, metformin and placebo were initially titrated to a maximum of 500 mg twice daily (1,000 mg/d average); older children received up to 850 mg twice daily (1,587 mg/d average).

Results

Metformin beat placebo, but not dramatically so. Patients on placebo had no weight loss over the 16-week trial, whereas those on metformin had an average decrease in BMI of 5%. Three of the 28 kids on metformin (11% of the sample) achieved an 8%–9% BMI reduction, but four children on metformin dropped out due to increased agitation, and one dropped out because of sedation. Gastrointestinal (GI) distress was also noted in 25% of those on metformin, versus less than 7% on placebo.

CCPR’s Take

These results are consistent with previous research on metformin and weight gain. It’s certainly useful to have additional data for our youngest patients with ASD. However, this is a small study, making it difficult to generalize. GI discomfort is a known side effect of metformin and is often cited as a reason for early discontinuation. It’s important to remember that children with ASD have a difficult time reporting physical discomfort: some may have suffered through 16 weeks of GI distress with no one the wiser.

PRACTICE IMPLICATIONS

Metformin may be a reasonable choice for reducing weight gain in your patients with ASD who need to be on an atypical antipsychotic, but any weight loss is likely to be rather small. If you are unsure whether metformin is appropriate for your patient, consult with an endocrinologist.