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Use of Antipsychotics in Alzheimer’s Patients May Lead to Detrimental Metabolic Changes

Science Update

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Atypical antipsychotic medications are associated with weight gain and other metabolic changes among patients with Alzheimer's disease, according to a recent analysis of data from the NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer's Disease (CATIE-AD) study. The study was published online ahead of print April 15, 2009, in the American Journal of Psychiatry.


Most of the data on the metabolic effects of atypical antipsychotics—also called newer or second generation antipsychotics—is from younger or middle-aged adults with schizophrenia. The metabolic effects on patients with Alzheimer's disease taking these medications have not been systematically assessed until now.

The CATIE-AD study compared the atypical antipsychotics olanzapine (Zyprexa), quetiapine (Seroquel) and risperidone (Risperdal) to a placebo (inactive pill) among 421 participants with Alzheimer's disease. Previously reported results from the CATIE-AD study found that the medications can benefit some patients in treating hallucinations, delusions, aggression and other similar symptoms, but they appear to be no more effective than a placebo when adverse side effects are taken into account. This most recent analysis, conducted by Ling Zheng, M.B.B.S., Ph.D. and Lon S. Schneider, M.D., of the University of Southern California, and colleagues, examined metabolic side effects associated with the medications.

Results of the study

During the first 12 weeks of the trial, olanzapine and quetiapine were significantly associated with weight gain—up to 0.14 pounds per week. Women gained more weight than men, and weight gain increased the longer a patient stayed on the medication. In addition, olanzapine was associated with a decrease in HDL (good) cholesterol and increased waist size. The researchers theorized that women gained more weight than men because older women tend to have more body fat and less lean body mass than older men, potentially making them more susceptible to the medications' metabolic side effects.


Previous results from CATIE-AD found only modest effectiveness in treating behavioral symptoms of Alzheimer's disease while adverse effects limited improvements overall. The results of this latest analysis suggest further caution is needed when using atypical antipsychotics to treat Alzheimer's patients. The researchers conclude that Alzheimer's patients receiving atypical antipsychotics should be monitored very closely.

What's next

Further studies are needed to better determine which Alzheimer's patients may benefit from use of atypical antipsychotics, and which may be more susceptible to serious side effects.


Zheng L, Mack WJ, Dagerman KS, Hsiao JK, Lebowitz BD, Lyketsos CG, Stroup TS, Tariot PN, Vigen C. Schneider L. Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients: the CATIE-AD study. American Journal of Psychiatry. Online ahead of print April 15, 2009.