Cochrane Briefs

Are Atypical Antipsychotics Safe in Patients with Alzheimer's Disease?


Am Fam Physician. 2006 Aug 1;74(3):414.

Clinical Question

Are atypical antipsychotic medications safe and effective for the treatment of behavioral and psychological disturbances in patients with Alzheimer's disease?

Evidence-Based Answer

Although the atypical antipsychotic medications risperidone (Risperdal) and olanzapine (Zyprexa) are modestly efficacious in reducing aggression, routine use is not justified. Both drugs are associated with serious adverse cerebrovascular events and extrapyramidal symptoms. Use of atypical antipsychotics in dementia significantly increases mortality (odds ratio [OR] = 1.7).

Practice Pointers

More than 50 percent of persons with Alzheimer's disease experience behavioral and psychological disturbances, which often are the stimulus for placement in residential or nursing home care. Antipsychotic medications have been used widely to mitigate these symptoms in patients with Alzheimer's disease, despite their known adverse effects. Because much data remain unpublished by pharmaceutical companies, the risk of serious adverse events from the use of atypical antipsychotics is not widely recognized.

Ballard and Waite systematically reviewed the published and unpublished literature on atypical antipsychotics in patients with Alzheimer's disease and found 16 randomized, double-blind studies that evaluated these agents. They concluded that, compared with placebo, there was a significant improvement in aggression in patients treated with risperidone or olanzapine and an improvement in psychosis in patients treated with risperidone. However, risperidone was associated with a significantly higher incidence of serious adverse cerebrovascular events (OR = 3.64; 95% confidence interval [CI], 1.72 to 7.69) and extrapyramidal side effects (for 2 mg daily, OR = 3.39; 95% CI, 1.69 to 6.80). Other adverse effects included somnolence, upper respiratory tract infections, edema, urinary tract infections, and fever. There were insufficient data to examine the impact of these medications on cognitive function.

In April 2005, the U.S. Food and Drug Administration (FDA) completed a meta-analysis1 of clinical studies assessing the use of atypical antipsychotics for the treatment of behavioral disorders in older patients with dementia. The results demonstrated a high death rate in patients treated with atypical antipsychotics compared with those receiving placebo.1 The FDA subsequently requested that the manufacturers of these drugs add a boxed warning to their drug labeling describing this risk and noting that these drugs are not approved for this indication.1

In practice, limited use of atypical antipsychotics in patients with Alzheimer's disease may be considered when patients display a serious, life-threatening risk to themselves or others. Nonpharmacologic treatment options include educating caregivers about managing behavioral symptoms, using lighting to reduce nighttime confusion and restlessness, simplifying tasks, and adhering to predictable routines.2 Sensory enhancement, social contact, behavior therapy, and environmental interventions3 also may decrease the occurrence of agitated behaviors. A clinical guideline3 on the nonpharmacologic management of dementia from the University of Iowa Gerontological Nursing Interventions Research Center is available at

The opinions and assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the U.S. Air Force or Department of Defense.


Ballard C, et al. Atypical antipsychotics for aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev. 2006;(1):CD003476.


1. U.S. Food and Drug Administration. Public Health Advisory. Deaths with antipsychotics in elderly patients with behavioral disturbances. April 11, 2005. Accessed May 9, 2006, at:

2. California Workgroup on Guidelines for Alzheimer's Disease Management. Guidelines for Alzheimer's disease management. Los Angeles, Calif.: Alzheimer's Association of Los Angeles, Riverside and San Bernardino Counties, 2002. Accessed May 9, 2006, at:

3. McGonigal-Kenney ML, Schutte DL. Non-pharmacologic management of agitated behaviors in persons with Alzheimer disease and other chronic dementing conditions. Iowa City, Iowa: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core, 2004. Accessed May 9, 2006, at:

The series coordinator for AFP is Clarissa Kripke, M.D., Department of Family and Community Medicine, University of California, San Francisco.



Copyright © 2006 by the American Academy of Family Physicians.
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