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Genetic link found to weight gain with antipsychotics

A study of antipsychotic drugs, some of the most commonly prescribed treatments, has found a genetic link to rapid weight gain in some patients who use the medications.

Researchers at the Feinstein Institute for Medical Research and Zucker Hillside Hospital, which are part of the Manhasset-based North Shore-LIJ Health System, said they have identified a gene that increases weight gain in people treated with drugs like risperidone, clozapine and aripiprazole, which go by the brand names Risperdal, Clozaril, FazaClo and Abilify.

The research could help doctors better serve patients who are genetically predisposed to the adverse effects of antipsychotic drugs, researchers said.

The class of drugs, known as second-generation antipsychotic medications, treat several conditions including schizophrenia, bipolar disorder, depression and even autism, said Anil Malhotra, a physician and investigator at Zucker and the Feinstein Institute.

He said extreme weight gain as a side effect of such drugs has been observed and documented in the past but researchers had not identified a genetic connection. For example, the website for Abilify, which is aripiprazole, said some users gained significant weight in a three-week trial.

Officials at Bristol-Myers Squibb, which manufactures Abilify, and the National Institute of Mental Health, did not respond to calls for comment on the study.

"This is the first time that a genetic-association study has been this successful in identifying a gene that predisposes the weight gain," Malhotra said. The findings appear in the Archives of General Psychiatry.

Malhotra added that between 10 percent and 30 percent of people carry the gene, called melanocortin 4 receptor, which has long been associated with obesity and type 2 diabetes.

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"Some people carry the risk form of the gene and some people don't," Malhotra said. "It's that subset of patients with the gene who are at greater risk for severe weight gain."

The study involved testing a discovery set of 139 subjects and then three more sets of subjects to compare results.

The subjects who gained weight packed on significant amounts, between 20 and 30 pounds on average, over the course of up to 12 weeks of treatment.

Malhotra said a simple saliva test could identify whether a patient has the gene associated with weight gain.He said he hopes the study helps doctors better cater treatment to the needs of patients.

"We have two goals," he said. "One is to identify new targets for drug development and secondarily to identify screening mechanisms by which to better personalize people's care. If I knew that an individual carried this risk genotype, perhaps there are alternative treatment strategies that we could use that would minimize their ultimate weight gain."

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