Fighting Antipsychotic Weight Gain

Jan. 8, 2008 -- The diabetes drug metformin -- especially with a diet/ exercise regimen -- largely reverses the weight-gain side effect of antipsychotic drugs.

Antipsychotic medications -- especially the newer atypical antipsychotics -- are effective treatments for a number of psychotic disorders and severe behavioral disturbances. But they have a dreaded side effect: significant weight gain.

Weight gain is a major reason why people suffering from psychosis die up to 30 years sooner than the general population. Recent studies have suggested that lifestyle intervention -- helping psychotic patients improve their diets and increase their exercise levels -- helps reduce weight gain.

Now a study of 128 newly diagnosed schizophrenic patients in China suggests that the older diabetes drug metformin has a dramatic effect on weight gain associated with antipsychotics. Ren-Rong Wu, MD, of Central South University in Changsha, China, and colleagues report the findings in the January 9/16 issue of The Journal of the American Medical Association.

"Lifestyle intervention and metformin alone and in combination demonstrated efficacy for antipsychotic-induced weight gain," Wu and colleagues conclude. "Lifestyle intervention plus metformin showed the best effect on weight loss. Metformin alone was more effective ... than lifestyle intervention alone."

The patients in the study had all gained more than 10% of their body weight after beginning antipsychotic treatment with Clozaril, Zyprexa, Risperdal, or sulpiride (used in Asia and Europe but not in North America).

The patients were randomly assigned treatment with metformin alone, metformin plus diet/exercise, inactive placebo alone, or inactive placebo plus diet/exercise.

After 12 weeks:

• Those assigned to placebo alone gained 6.8 pounds. Their waist size grew by nearly an inch.
• Those assigned to placebo plus diet/exercise lost 3.1 pounds. Their waist size shrank by a tiny fraction of an inch.
• Those assigned to metformin alone lost 7.1 pounds. Their waist size shrank by a half-inch.
• Those assigned to metformin plus diet/exercise lost 10.4 pounds. Their waist size shrank by nearly an inch.

All of the patients in the study had only recently begun low-dose antipsychotic treatment; none had yet become obese. It's not yet clear whether obese patients or those on long-term, high-dose antipsychotic treatment will obtain similar results from metformin treatment.