Nonsignificant Weight Gain With Atypical Antipsychotics in Men With Alzheimer’s Disease: An Important Result of the CATIE-Alzheimer’s Disease Study

To the Editor: We read with great interest the article by Ling Zheng, M.B.B.S., Ph.D., et al., published in the May 2009 issue of the Journal(1) . The authors commented that Alzheimer’s disease patients who received treatment with second-generation antipsychotics should be monitored closely for metabolic effects. However, discussion regarding the important finding of nonsignificant weight gain with antipsychotics among male subjects would have been very informative.

Behavioral symptoms of dementia, such as wandering, aggression, and inappropriate activity (2) , may increase energy expenditure and reduce intake, such that improvement in behavioral and psychiatric symptoms may have contributed to the weight outcome in this study. Hence, an analysis of how behavioral change interacted with weight would have been useful, as well as an analysis of gender interactions with these variables. Baseline Brief Psychiatric Rating Scale scores were provided, but follow-up scores at the end of phase 1 would have helped to address this issue. Furthermore, osteoporosis and arthritis are common in elderly women, making them more sedentary with less energy expenditure (3) , which may explain their weight gain.

In addition to the importance of behavioral measures and their potential effect on weight, further information regarding the treatment status of the participants would have also been helpful. The article stated that 349 subjects received antipsychotics for at least 1 day (73 [21%], 63 [18%], and 61 [17%] patients received olanzapine, quetiapine, and risperidone alone, respectively). What other antipsychotics did the remaining 152 (43.5%) patients in the total sample receive?

Despite these questions, we commend the authors for their use of a prospective follow-up design and proper diagnostic assessment measures, making this study a valuable research contribution. Finally, we would like to suggest that cross-cultural studies are required before definite conclusions can be made about the metabolic side effects of atypical antipsychotics in Alzheimer’s disease patients.