In a small new study, a commonly used diabetes drug curbed the troublesome weight gain that is a common side effect of the only two medicines approved for reducing agitation in children and teens with autism.
The promising results of the study – which took place at four centers in the Autism Speaks Autism Treatment Network (ATN) – appear in the latest issue of JAMA Psychiatry. The research was made possible by the ATN’s federally funded role as the nation’s Autism Intervention Research Network for Physical Health.
Risperidone (brand name Risperdal) and aripiprazole (Abilify) are the only medicines approved by the U.S. Food and Drug Administration for reducing agitation and irritability in children with autism spectrum disorder (ASD). These medicines become important when serious agitation – including aggression – does not respond to non-drug, behavioral therapy. However, both risperidone and aripiprazole commonly produce significant weight gain – a worrisome side effect given obesity’s many associated health risks.
Controlling a serious side effect of autism medications
"It's critically important that we investigate new ways to support healthy outcomes as early as possible for those who are on these medications," says pediatric neurologist Evdokia Anagnostou, the study’s principal investigator and co-director of the Autism Speaks ATN at Toronto’s Holland Bloorview Kids Rehabilitation Hospital. "Use of antipsychotics to help manage irritability associated with ASD can sometimes be long-term, which means we need to provide families with solutions that support lasting optimal health in their children," she emphasizes.
Over the course of 16 weeks, the researchers tracked changes in body mass and performed blood work on 60 study participants, ages 6 to 17. Twenty-eight of the children and teens took the diabetes drug metformin in addition to their usual dose of risperidone or aripiprazole. The rest took an inactive placebo pill along with their behavioral medicines. Neither the researchers nor the participating families knew who received the metformin and who received the dummy treatment until the end of the study.
A clear difference in weight control
As a group, those taking the placebo continued to gain weight over the course of the trial. By contrast, the group taking metformin saw an overall reduction in weight. Most remarkably, three participants taking metformin experienced an 8 to 9 percent decrease in body mass. The researchers saw no changes in obesity-associated metabolic measures such as insulin sensitivity and cholesterol. The 16-week study period may not have been long enough to detect such health benefits, they write.
Overall, the metformin was “well-tolerated,” the researchers report. However, as a group, those taking metformin had more days of gastrointestinal issues such as constipation and diarrhea than did those taking the placebo. (This side effect was not associated with individual weight loss.) In addition, the researchers discontinued metformin in five children because of increased agitation or sedation that may or may not have been caused by the drug.
Given the promising results of this small pilot study, the researchers call for follow-up studies enrolling more children for longer periods.
“Medications such as risperidone and aripiprazole are appropriate only for severe behavioral problems when non-drug approaches have not been adequate,” adds developmental pediatrician Paul Wang, Autism Speaks’ head of medical research. “It’s good to know that metformin has the potential to help manage the weight gain that often accompanies these medications.” (Dr. Wang was not directly involved in the study.)
The Autism Speaks ATN centers participating in the study included the Holland Bloorview Kids Rehabilitation Hospital, in Toronto; Ohio State University Wexner Medical Center and Nationwide Children’s Hospital, in Columbus; the University of Pittsburgh; and Vanderbilt University, in Nashville.
For more on this study, see the video below, courtesy The Ohio State University Wexner Medical Center.