Metformin and Counseling Retard Drug-Induced Weight Gain in Schizophrenia

By Tony Cappasso
CHANGSHA, China, Jan. 9 -- For patients with schizophrenia taking antipsychotics, metformin or lifestyle counseling, or both combined, helps steer clear of drug-induced weight gain and insulin resistance, found investigators here.
In a randomized 12-week trial of 128 adults with schizophrenia, age 18 to 49, who had gained more than 10% of their pre-antipsychotic weight, metformin alone was more effective than lifestyle intervention alone, found Jing-Ping Zhao, M.D., Ph.D., and colleagues at the Second Xiangya Hospital here.
But a combined approach produced the better results, the research team reported in the Jan. 9/16 issue of the Journal of the American Medical Association.
Participants taking antipsychotic medications were randomized to one of four groups: 12 weeks of placebo, 750 mg/day of metformin alone, 750 mg/day of metformin with lifestyle intervention, or lifestyle intervention alone.
The lifestyle interventions included counseling and dietary and exercise programs, the researchers reported. Caregivers reported participants' food intake and exercise levels, the authors said.
"We found statistically significant decreases in mean weight, body mass index, waist circumference, insulin, and insulin resistance index among patients in the lifestyle-plus-metformin, metformin-alone, and lifestyle-plus-placebo groups," they wrote.
Participants taking metformin in combination with lifestyle counseling lost 7.3% of their body weight (95% CI: 3.4 to 5.7 kg) and had average decreases of 1.8 in BMI ((95% CI: 1.3 to 2.3), 3.6 in insulin resistance index, and lost 2 cm in waist circumference.
Participants in the metformin-alone group also had weight decline by 4.9% (mean, 3.2 kg, 95% CI: 2.5 to 3.9 kg) and improvements in their BMI of 1.2 (95% CI: 0.9 to 1.5), as well as decreases of 3.5 in insulin resistance index, and 1.3 cm in waist circumference, the researchers reported.
In the lifestyle-plus-placebo group, participants had average decreases of 0.5 in BMI, and 1.0 in insulin resistance index, they said.
Weight continued to climb in the placebo-only group and other measures continue to deteriorate, showing increases in all measurements, including 1.2 in BMI, 0.4 in IRI, and 2.2 cm in waist circumference (95% CI: 2.4 to 3.8 kg), they reported.
Weight gain in patients taking antipsychotic medications has become a source of concern for physicians, Dr. Zhao wrote, especially in light of potentially serious adverse metabolic affects, including hyperlipidemia and glucose intolerance.
"According to a recent study, 78.8% of patients receiving antipsychotic agents increased their baseline weight by more than 7%," Dr. Zhao and colleagues noted.
Recent studies, he noted, suggest that early death is a major concern in patients with severe mental illnesses, showing that they may die up to three decades earlier than those in the general population.
"Heart disease is a leading cause of death in these patients," he said, adding, "One of the major risk factors for heart disease and early death in these patients is weight gain."
The authors noted several limitations of the study, including the short duration, the fact that all enrolled patients were taken care of by their patients or caregivers, which improved adherence, low doses of antipsychotics, and the use of a fixed dose of metformin.
They also pointed out that the study may not be generalizable to Western populations and "as first episode schizophrenia patients with less than a year of illness, patients in our study were young and few were obese, so we do not know whether these interventions would have the same effect on obese, older, or long-term patients."
The research was supported by National Key Technologies R&D Program in the 10th five-year-plan from the Ministry of Science and Technology of the People's Republic of China.
Primary source: Journal of the American Medical AssociationSource reference:Wu R-R, "Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain: a randomized controlled trial" JAMA 2008; 299: 185-193.