New Research Shows How Antipsychotic Drugs Cause Weight Gain

(February 2, 2007) -- Scientists say they have pinpointed a mechanism in the brain that helps explain why certain antipsychotic drugs can trigger increased appetite and potentially dangerous weight gain in patients.

The side effect has cast a cloud on newer and more powerful drugs, such as Eli Lilly & Co.'s Zyprexa, used to treat schizophrenia and other mental illnesses. Significant weight gain increases the risk of life-threatening complications, including heart disease and diabetes.

Histamine may help spur the weight gain seen in patients taking certain kinds of antipsychotic drugs, researchers say.

In some cases, patients taking these drugs to treat mental illness gain so much weight that they develop serious complications such as heart disease and diabetes.

"We've now connected a whole class of antipsychotics to natural brain chemicals that trigger appetite. Our identification of the molecular players that link such drugs to increased food intake means there's now hope for finding a newer generation of drugs without the weight-gain side effects," Dr. Solomon H. Snyder, professor of neuroscience at the Johns Hopkins School of Medicine in Baltimore , said in a prepared statement.

The latest study, appearing in the Proceedings of the National Academy of Sciences, links a class of antipsychotics to brain chemicals that regulate appetite. The mechanism was discovered in mice. A similar link still needs to be established in people.

"If we understand why the drugs make you fat, we can design drugs that don't do that," said Snyder.

The Hopkins team suspected that certain antipsychotic drugs might trigger an overreaction in AMPK, an enzyme in brain cells that controls appetite in mice and likely does the same in humans.

To test this theory, the researchers injected mice with clozapine (Clozaril), a drug commonly prescribed to treat schizophrenia and bipolar disorders in people who respond poorly to conventional drugs.

AMPK activity quadrupled in the mice after they were given clozapine, the researchers report.

As their research progressed, the Hopkins team focused on a link between a histamine receptor, clozapine, AMPK activity and appetite. They injected clozapine into mice genetically engineered to lack the histamine receptor. The mice showed no increase in AMPK activity.

Histamine is already well known for its role in triggering allergy symptoms.

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"Histamine also has a long history as a suspect in weight control, but no one ever could put a finger on the exact link," Snyder said. "The connection we've made between its receptor and appetite control is incredibly intriguing and opens new avenues for research on weight control, possibly including drugs that suppress appetite safely."

The study is expected to be published online in this week's issue of the Proceedings of the National Academy of Sciences.

Source: HealthyDay News

Last updated: 02/07

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