Antipsychotic Drug Causes Weight Gain

Ivanhoe Newswire
Wednesday, February 14, 2007; 12:00 AM

By Lucy Williams, Ivanhoe Health Correspondent

ORLANDO, Fla. (Ivanhoe Newswire) -- Some patients undergoing treatment for mental illness gain so much weight they develop life-threatening health complications.

Clozapine (Clozaril), a common treatment for schizophrenia and bipolar disorder, can cause massive weight gain in patients.

"This is so severe of an issue that patients refuse to take the drugs," Solomon Snyder, M.D., professor of neuroscience at the Johns Hopkins School of Medicine in Baltimore, told Ivanhoe. "They'd rather be schizophrenic than have such a terrible weight gain."

Recent research from Johns Hopkins reveals the cause of this potentially dangerous side effect. A class of antipsychotic medications boosts the production of natural brain chemicals that trigger appetite.

AMPK is a functional enzyme expressed in a number of tissues, including the brain. Previous research suggested increased levels of AMPK can spike appetite in mice -- and possibly in humans.

Researchers injected mice with clozapine. Following injection, AMPK activity in the mice quadrupled. When researchers blocked a receptor site for histamine, AMPK levels increased at a similar rate. Mice genetically modified to have no histamine receptor experienced no change in AMPK levels when given clozapine.

"The most effective [antipsychotic drugs], such as clozapine and Zyprexa [olanzapine], block histamine H1 receptors the most and thus cause the greatest weight gain," Dr. Solomon said.

Researchers report they must develop antipsychotic drugs that do not block histamine H1 receptors.

"In the drug industry, it's very easy for a chemist to tailor new molecules to block or not to block receptors, so it would be very easy to make modified molecules that will still be antipsychotic but won't block histamine receptors and won't cause weight gain," said Dr. Solomon. "This would decrease very serious adverse effects of massive weight gain."

This article was reported by Ivanhoe.com, which offers Medical Alerts by e-mail every day of the week. To subscribe, click on: http://www.ivanhoe.com/newsalert/.

SOURCE: Ivanhoe interview with Solomon Snyder, M.D.; The Proceedings of the National Academy of Sciences, published online Feb. 2007