Lifestyle intervention and the drug metformin are both effective against antipsychotic-induced weight gain, and treatment is most effective when the two therapies are combined, according to a study in the January 9/16 issue of JAMA.

Atypical antipsychotic (AAP) medications have been used increasingly for the management of patients with a variety of psychotic disorders and severe behavioral disturbances. But in the past decade, there has been a growing concern among clinicians and researchers that use of AAP medications may be related to potentially serious adverse metabolic effects, including weight gain, hyperlipidemia (high fat levels in the blood), and glucose intolerance. Metformin is a drug used to treat type 2 diabetes. It inhibits glucose production, is well tolerated, and prevents continual weight gain while it decreases measures of insulin resistance. Some studies find that metformin can reduce body weight in patients with type 2 diabetes and in obese people who do not have diabetes, according to background information in the article.

Ren-Rong Wu, M.D., of the Mental Health Institute of the Second Xiangya Hospital, Central South University, China, and colleagues conducted a randomized controlled trial from October 2004 to December 2006 to test the efficacy of lifestyle intervention and metformin alone and in combination for antipsychotic-induced weight gain and abnormalities in insulin sensitivity. The study included a total of 128 adult patients with schizophrenia. Participants who gained more than ten percent of their pre-drug weight were assigned to one of four treatment groups.

The patients continued their antipsychotic medication and were randomly assigned to 12 weeks of placebo, 750 milligrams per day of metformin alone, 750 milligrams per day of metformin with lifestyle intervention, or lifestyle intervention alone. Lifestyle interventions included psycho-educational, dietary, and exercise programs.

“In this 12-week study, we found statistically significant decreases in mean weight, BMI [body mass index], waist circumference, insulin, and IRI [insulin resistance index] among patients in the lifestyle-plus-metformin, metformin-alone, and lifestyle-plus-placebo groups, but not among those in the placebo-alone group whose measurements continued to increase,” the authors write.

Those taking metformin in combination with lifestyle intervention had average decreases of 1.8 in BMI, 3.6 in IRI, and two centimeters in waist circumference. Those taking metformin alone showed average decreases of 1.2 in BMI, 3.5 in IRI, and 1.3 centimeters in waist circumference. In the lifestyle-plus-placebo group, participants had average decreases of 0.5 in BMI, and 1.0 in IRI. Participants in the placebo group continued to show increases in all measures: 1.2 in BMI, 0.4 in IRI, and 2.2 centimeters in waist circumference.

“Lifestyle intervention and metformin alone and in combination demonstrated efficacy for antipsychotic-induced weight gain. Lifestyle intervention plus metformin showed the best effect on weight loss,” the authors conclude. “Metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone.”

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(JAMA. 2008;299(2):185-193. Available pre-embargo to the media at www. jamamedia.org)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Contact: Hua Jin, M.D.
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