The diabetes medication metformin hydrochloride was associated with decreased weight gain in a small clinical trial of children and adolescents with autism spectrum disorder who were taking atypical antipsychotics to treat symptoms of irritability and agitation, according to an article published online by JAMA Psychiatry.
The atypical (newer) antipsychotic medications risperidone and aripiprazole are the only treatments the U. S. Food and Drug Administration has approved for use in autism spectrum disorder (ASD). While the medications can improve symptoms of irritability and agitation in children, the medicines also cause weight gain. Over time, that can increase the risk of diabetes. In adults, metformin has been associated with stopping or reversing the weight gain associated with atypical antipsychotics.
Evdokia Anagnostou, M.D., of the Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada, and coauthors conducted a 16-week clinical trial to test the efficacy of metformin for weight gain associated with atypical antipsychotics in children and adolescents with ASD.
The clinical trial assigned 61 participants (average age almost 13) to receive either metformin or placebo twice daily. Of the 61 participants, 60 initiated treatment. The study's main outcome measure was change in body mass index (BMI) z score over 16 weeks of treatment as a reflection of weight gain. They also looked at other body composition and metabolic variables, as well as safety and tolerability.
The authors report metformin was better than placebo in reducing weight gain associated with atypical antipsychotics, as assessed by change from baseline to week-16 BMI z scores (metformin vs placebo difference of - 0.010).
Of the 28 participants in the metformin group who initiated treatment, three participants (11 percent) saw declines of 8 percent to 9 percent in BMI. No other participants experienced declines of more than 5 percent in BMI during the 16-week treatment, according to the results. No significant differences were noted in metabolic variables.
The authors report that, overall, metformin was well tolerated, although participants experienced gastrointestinal adverse events during a higher percentage of treatment days.
Study limitations include a small group of participants and a too short period of time to evaluate whether the initial improvement can be maintained.
"These findings have important implications for children in whom the benefits of atypical antipsychotics for treating irritability and agitation symptoms are difficult to balance with the substantial weight gain that often accompanies their use," the study concludes.
Article: Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder, Evdokia Anagnostou, Michael G. Aman, Benjamin L. Handen, Kevin B. Sanders, Amy Shui, Jill A. Hollway, Jessica Brian, L. Eugene Arnold, Lucia Capano, Jessica A. Hellings, Eric Butter, Deepali Mankad, Rameshwari Tumuluru, Jessica Kettel, Cassandra R. Newsom, Stasia Hadjiyannakis, Naomi Peleg, Dina Odrobina, Sarah McAuliffe-Bellin, Pearl Zakroysky, Sarah Marler, Alexis Wagner, Taylor Wong, Eric A. Macklin, Jeremy Veenstra-VanderWeele, JAMA Psychiatry, doi:10.1001/jamapsychiatry.2016.1232, published online 24 August 2016.