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In a randomized trial, children taking metformin experienced greater weight loss following weight gain when taking antipsychotic medications to manage autism spectrum symptoms.

, of Bloorview Research Institute in Toronto, and colleagues, reported that compared with the placebo group, whose weight was constant, the sixty children taking metformin experienced significant reduction in weight gain, defined by week-to-week BMI z scores.

Metformin was also linked to improvements in BMI and weight, but not in metabolic variables, they wrote in .

Atypical antipsychotic medications, such as risperidone (Risperdal) and aripiprazole (Abilify), have been used to treat behavioral symptoms associated with autism, but these medications can also and potentially,

Anagnostou and colleagues noted that, to their knowledge, there has been no prior research on the "treatment and prevention" of weight gain in children with autism spectrum disorder. But metformin has been studied for the general treatment of weight gain in children, and has been shown to stop weight gain in adults who take atypical antipsychotics for autism spectrum disorder, thus prompting the current trial. Mean participant age was 12.8 years; 75% were boys.

BMI z score from was reduced significantly from baseline through the 16-week trial in the metformin group versus the placebo group (metformin versus placebo difference -0.010, 95% CI -0.16 to -0.04, P=0.03). The majority of the metformin group experienced no more than a 5% reduction in BMI, though three participants in the metformin group experienced 8% to 9% declines.

Certain secondary outcomes also saw significant improvements, with reductions in BMI (-0.95, 95% CI -1.46 to -0.45) and weight (-2.73 kg, 95% CI -4.04 to -1.43, P<0.001 for both) for the metformin group compared with placebo.

, of Keck School of Medicine of USC in Los Angeles, who was not involved with the research, noted that this effect did not seem associated with any changes in body composition, insulin sensitivity, or lipid parameters.

"The authors appropriately suggest the need for additional research in this area including a study in which metformin and atypical antipsychotic medications are started concomitantly before weight gain occurs," said Geffner in an email to 乌鸦传媒. "While these preliminary data are intriguing, further studies need to consider the effect of puberty, the use of more sophisticated measures of body composition, and other types of data analysis, especially for insulin sensitivity."

There were also no significant between-group differences associated with behavioral scores. There was one serious adverse event involving the hospitalization of a patient for aggression, which was unrelated to the study drug. The metformin group had gastrointestinal adverse events (abnormal feces) on a significantly higher portion of treatment days compared with the placebo group -- though the authors determined that was not related to the weight loss experienced by that group.

Limitations to the study include the length of metformin treatment being inadequate to capture the drug's metabolic benefits, and that the overall study length itself was too short, with too small a sample size.

An by , argued that given the prevalence of weight gain associated with atypical antipsychotic use in children, "alternative strategies" may be needed other than metformin. He cited , an epilepsy and migraine treatment drug known to cause appetite suppression.

He also suggested ziprasidone (Geodon) monotherapy. Ziprasidone is an atypical antipsychotic that has not been associated with weight gain, though McDougle acknowledged some potential drawbacks of the treatment.

"A primary reason that ziprasidone has not been studied in a systematic manner as a treatment for irritability in ASD likely relates to the drug's effects on the length of time it takes the electrical system in the heart to repolarize, adjusted for heart rate (QTc interval)," he wrote. "Although data generated over the last decade suggest an increased risk for sudden death in adults taking atypical antipsychotics, there is no evidence for a heightened risk for children and adolescents."

McDougle added that ziprasidone "has been shown to be efficacious and safe for treating children and adolescents with Tourette syndrome and pediatric bipolar I disorder" with no increased risk of sudden cardiac death.