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Am Fam Physician. 2006;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 Because much data remain unpublished by pharmaceutical companies, the risk of serious adverse events from the use of atypical antipsychotics is not widely recognized.

Ballard and Waite systematically reviewed the published and unpublished literature on atypical antipsychotics in patients with Alzheimer's disease and found 16 randomized, double-blind studies that evaluated these agents.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

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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