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Atypical Antipsychotic Drugs in Alzheimer Patients

They were somewhat more effective but also more toxic than placebo.

Patients with Alzheimer disease often receive so-called atypical antipsychotic drugs, but the balance of benefit and harm remains controversial. Indeed, an FDA advisory in 2005 noted that antipsychotic drugs can increase mortality among older demented patients (Journal Watch Dec 16 2005).

In this 36-week, double-blind, multicenter, randomized U.S. trial, 421 outpatients with Alzheimer disease and psychosis, aggression, or agitation received olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), or placebo. Study physicians were permitted to adjust doses, and drugs could be stopped after 2 weeks in nonresponders.

The primary endpoint, drug discontinuation for any reason, did not differ significantly among the four groups. Median time to drug discontinuation was similar among the groups (range, 5–8 weeks); about 80% of subjects in each group eventually discontinued their drug during the study. Drug discontinuation due to lack of efficacy occurred less often in the three active-drug groups than in the placebo group (olanzapine and risperidone appeared somewhat more effective than quetiapine), but this effect was offset by more frequent drug discontinuation due to side effects in the active-drug groups.

Comment: In this study, atypical antipsychotic drugs were somewhat more effective but also more toxic than placebo. The primary endpoint (drug discontinuation for any reason) is a useful and clinically obvious indicator of the overall success of drug therapy. Although these findings do not invalidate therapeutic trials of these drugs in appropriately selected patients with Alzheimer disease, they do suggest that clinicians should think twice before treating such patients with antipsychotic drugs.

— Allan S. Brett, MD

Published in Journal Watch General Medicine October 11, 2006

Citation(s):

Schneider LS et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med 2006 Oct 12; 355:1525-38.

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Karlawish J. Alzheimer's disease — Clinical trials and the logic of clinical purpose. N Engl J Med 2006 Oct 12; 355:1604-6.

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• Medline abstract (Free)