Antipsychotic Drugs for Dementia Have Adverse Effects

Elderly patients with Alzheimer's disease who are treated with second-generation antipsychotics should be monitored closely for weight gain and lipid abnormalities, according to an analysis of data from the Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer's disease (CATIE-AD).

The 36-week trial included 421 outpatients with Alzheimer's disease who were treated for delusions and aggression. The average patient age was 78 years and 56 percent were female. The findings are reported in the online edition of the American Journal of Psychiatry.

Seventy-two patients had no exposure to the study drugs, while the remaining subjects were assigned to treatment with olanzapine (Zyprexa) , quetiapine (Seroquel), and risperidone (Risperdal); they could switch antipsychotic medication during the trial.

Female subjects gained an average of 0.14 pounds per week and body mass index increased by 0.03 per week, Dr. Lon S. Schneider at the University of Southern California, Los Angeles, and associates report. Changes in weight and BMI among males were not statistically significant.

The duration of antipsychotic use by women was significantly associated with weight gain. "The prevalence of significant weight gain was 10 percent, 17 percent, and 20 percent among patients with less than 12 weeks, 12 to 24 weeks, and greater than 24 weeks of use compared to 7 percent with no use," Schneider's team reports.

The effect on weight was significant for olanzapine and quetiapine, but less so for risperidone. Olanzapine was also significantly associated with increased waist circumference and decreased HDL cholesterol - the "good" cholesterol.

The metabolic changes that correlated with treatment with a second-generation antipsychotic drug were of similar magnitude to those observed in younger people with schizophrenia, the team notes.

The results from a previous analysis of the CATIE-AD data indicated that the drugs did not improve patients' function and quality of life and did not decrease their need for care.

The worsening cardiac and metabolic risks among these Alzheimer's patients are "particularly concerning," they add, and likely explain the increased risk of mortality seen with these drugs.