Antipsychotics tied to adiposity, insulin resistance in children

ADA 71st Scientific Sessions

SAN DIEGO — Three commonly used antipsychotic medications increase body fat and insulin sensitivity in children.

Research has linked various mental health therapies to higher risks for diabetes and obesity in adults, but studies are lacking in the pediatric population, according to John W. Newcomer, MD, professor of psychology and medicine at Washington University of St. Louis in Missouri. He and researchers for the Metabolic Effects of Antipsychotics in Children study sought to fill this gap in knowledge by investigating the metabolic effects of three frequently prescribed antipsychotic medications:

• aripiprazole (Abilify, Otsuka Pharmaceuticals);
• olanzapine (Zyprexa, Eli Lilly); and
• risperidone (Risperdal, Johnson & Johnson).

Newcomer and the researchers examined changes in body fat percentage and insulin sensitivity after 12 weeks of antipsychotic therapy in a group of children aged 6 to 18 years with disruptive behavior disorders.

Results linked all three drugs with changes in adiposity, according to Newcomer.

“The overall figures [measured by DXA] show 2.5% in body fat percentage and, highly significantly, about a two and one-third kilogram increase in body fat overall,” he said at the oral presentations symposium.

These changes differed among the individual medications. Approximately one-quarter of children using aripiprazole and risperidone experienced small increases or slight decreases in body fat percentage; in contrast, body fat increased in virtually all children using olanzapine.

At baseline, the percentage of children who were overweight or obese was on par with the general population, Newcomer noted.

“It was after the short, 12-week duration of treatment that we saw the overall percentage children who were overweight or obese go from one-third to nearly 48%.”

The researchers also found considerable reductions in whole-body insulin sensitivity among these children. Again, Newcomer said, olanzapine was associated with the greatest decline in insulin sensitivity.

Despite these adverse metabolic effects, the children experienced significant psychological benefits, with pooled mean Aberrant Behavior Checklist irritability/aggression subscale scores decreasing by 16.64 points.

Careful selection of patients and the types of antipsychotic medications used may prevent the adverse metabolic effects that some of these drugs have in children with mental health issues, the researchers concluded.

“These medications … are associated with different levels of risk for changes in adiposity and insulin sensitivity,” Newcomer said. “Clinicians can beneficially modify risk by judicious selection of who’s going to be treated and perhaps which medications are used.” – by Melissa Foster

For more information:

• Newcomer JW. 0128-OR. Presented at: American Diabetes Association’s 71st Scientific Sessions; June 24-28, 2011; San Diego, Calif.

Disclosure: Dr. Newcomer reports being a board member or on the advisory panel for AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma Co, H. Lundbeck A/S, Janssen Pharmaceuticals, OBEcure, Organon (Schering-Plough), Otsuka Pharmaceuticals, Pfizer, Schering Plough, Solvay, Vivus and Wyeth. He also reports receiving consulting fees from H. Lundbeck A/S, OBEcure and Pfizer. He receives research report from Bristol-Myers Squibb, Janssen Pharmaceuticals and Pfizer.

Second-generation antipsychotics are indicated for the treatment of irritability associated with autism and acute treatment of bipolar mania and schizophrenia in children. Second-generation antipsychotics are also used off-label for other behavioral disorders in children. Numerous studies have linked the use of second-generation antipsychotics with significant weight gain, increased blood glucose and cholesterol levels, and endocrine abnormalities in adults; however, studies in pediatric populations have been limited. The study presented was a randomized safety-efficacy trial involving children aged 6 to 18 years with disruptive behavior disorders who were treated with12 weeks of antipsychotic therapy using one of three commonly prescribed second-generation antipsychotic medications (aripiprazole, risperidone, olanzapine). Rigorous metabolic assessments were performed. Treatment resulted in marked improvement in behavioral checklist scores; however, short-term use of antipsychotics was also associated with significant increases in adiposity and decreases in whole-body insulin sensitivity. Olanzapine use was associated with the worst metabolic profile. Careful monitoring of metabolic adverse effects in children receiving second-generation antipsychotic medication and judicious selection of patients requiring treatment are warranted.

– Elaine H. Morrato, DrPH, MPH, CPH

Assistant Professor

Children’s Outcomes Research Program

University of Colorado School of Medicine

Disclosure: Dr. Morrato has received research support from Ortho-McNeil-Janssen Pharmaceuticals.

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