Study identifies cause of weight gain from antipsychotic drugs

A negative side effect of a major class of antipsychotic drugs is weight gain, which can lead to Type 2 diabetes.
By Amy Wallace  |  Aug. 15, 2017 at 10:29 AM
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Aug. 15 (UPI) -- Researchers have identified the cellular receptor that causes weight gain from antipsychotic drugs, helping them reverse the effect in laboratory mice.

One of the negative side effects of antipsychotic medication is that it can often cause patients to gain unwanted weight.

A team from the University of Texas Southwestern Medical Center found that the serotonin 2c receptor is responsible for weight gain patients experience when taking antipsychotic drugs for depression and schizophrenia.

"Atypical antipsychotics are essential medications for millions of schizophrenia patients worldwide and they are increasingly being prescribed for bipolar disorder, major depressive disorder, and autism," Dr. Chen Liu, an assistant professor of Internal Medicine and Neuroscience, said in a news release.

"Most members of this class of antipsychotics are linked to a drug-induced metabolic syndrome characterized by excessive weight gain, blood fat abnormalities, and type 2 diabetes. Obesity and diabetes often develop shortly after treatment begins."

Researchers administered the drug olanzapine to mice in a laboratory setting over a six-week period. The exposure caused weight gain, especially in female mice, from increased body fat.

"Similar to treatment in humans, mice given olanzapine showed significant weight gain, higher food intake, and metabolic changes associated with insulin resistance and diabetes," Dr. Caleb Lord, a former postdoctoral researcher in the Division of Hypothalamic Research, said.

The study showed that genetically modified mice that lacked the serotonin 2c receptor did not have an increase in blood sugar or weight gain.

"Our study directly demonstrates in a mouse model that this interaction with the serotonin 2c receptor is a major cause of olanzapine's metabolic side effects," Liu said. "This finding is clinically significant because of an FDA-approved weight loss drug called lorcaserin, which in contrast to olanzapine, activates the serotonin 2c receptor. Based on the opposite effects of lorcaserin and olanzapine on the serotonin 2c receptor, we wanted to test whether lorcaserin treatment could counteract the metabolic effects of olanzapine. Co-treating with lorcaserin prevented weight gain and significantly improved the metabolic profile of mice treated with olanzapine."

The study was published Monday in the Journal of Clinical Investigation.

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