Weight gain puzzle from antipsychotic drug solved

Last Updated: 2007-02-13 9:58:02 -0400 (Reuters Health)

By Will Dunham

WASHINGTON (Reuters) - Researchers in Baltimore have pinpointed the reason some drugs used to treat mental illnesses, such as schizophrenia, cause patients to gain a lot of weight, raising hope for developing drugs without this side effect.

Antipsychotic medications such as Zyprexa, made by Eli Lilly and Co., increase the activity of an enzyme called AMPK in cells in the part of the brain that regulates eating behavior, according to the results of a mouse study.

"It's a big increase and it occurs with very little doses of the drug," Dr. Solomon Snyder, professor of neuroscience at Johns Hopkins School of Medicine, said in an interview.

The study was published in the Proceedings of the National Academy of Sciences.

Zyprexa's use has been crimped by concerns over weight gains.

Patients using antipsychotic drugs tend to put on so many pounds that they are at heightened risk for serious complications including diabetes and heart disease.

The use of these drugs "has been hampered primarily by the fact that for some of them there is this horrible gain, largely due to just eating too much from increased appetite," Snyder said.

"Unfortunately, Zyprexa, which everybody agrees is the best therapeutic agent, (causes) the worst weight gain, along with clozapine, the parent drug in the class. And it was sort of a puzzle," Snyder added.

The researchers also showed that AMPK's increase was because the antipsychotic drugs were interfering with the important protein histamine, which is involved in allergy symptoms and long has been suspected to have a role in weight control.

Snyder said the findings point to the possibility of developing a new generation of antipsychotic drugs that are effective but do not cause weight gain.

Clozapine is sold as Clozaril by Novartis AG.