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Director’s Update: NIMH Perspective on Treating Alzheimer’s Patients with Antipsychotic Medications

The recent publication of phase 1 results from the NIMH-funded Clinical Antipsychotic Trials in Intervention Effectiveness for Alzheimer's disease (CATIE-AD) in the New England Journal of Medicine provides new information about the use of several "atypical" antipsychotic medications for the treatment of psychotic symptoms in patients with Alzheimer's disease.

Approximately 75 percent of Alzheimer's patients experience psychotic symptoms such as hallucinations, and behavioral symptoms such as aggression and agitation.1 The U.S. Food and Drug Administration has not approved the use of antipsychotic medications for treating psychosis or agitation among Alzheimer's patients, citing safety concerns. In the absence of a better pharmacological alternative, however, antipsychotic medications are widely used on an off-label basis. In fact, it is estimated that 25 percent of Medicare beneficiaries in nursing homes receive these medications.2

The extent to which these medications benefit patients is unclear, and opinions vary as to whether they are safe for this population. The results of phase 1 of CATIE-AD provide a first set of real-world effectiveness data where little existed before. Overall, data from this trial suggest:

  • Although some atypical antipsychotic medications are modestly helpful for some patients, they are not effective for the majority of Alzheimer's patients with psychotic symptoms.
  • Good clinical practice requires that medical or environmental causes for Alzheimer's-related agitation and aggression be ruled out and that behavioral interventions be considered before turning to antipsychotic medications.
  • If an antipsychotic medication then is warranted, clinicians should closely monitor their Alzheimer's patients for intolerable side effects and potential safety concerns.
  • Clinicians should be mindful of the limitations of these medications and weigh the risks against potential benefits.

Clinical research data indicate that other medications — such as antidepressants, anxiety medications, sedatives, and mood stabilizers — that are commonly used to manage psychotic symptoms in Alzheimer's patients, also have significant limitations and risks. Therefore, developing policy that could severely limit physician and patient use of atypical antipsychotic medications would not be in the best interest of these patients. More research is needed to identify the subset of patients who will most likely benefit from and tolerate these medications, and to develop better treatments for this vulnerable population.

1. Devanand DP, Jacobs DM, Tang MX, et al. The course of psychopathologic features in mild to moderate Alzheimer disease. Archives of General Psychiatry 1997;54:257-63.

2. The Quality of Antipsychotic Drug Prescribing in Nursing Homes, Becky A. Briesacher; M. Rhona Limcangco; Linda Simoni-Wastila; Jalpa A. Doshi; Suzi R. Levens; Dennis G. Shea; Bruce Stuart, Arch Intern Med. 2005;165:1280-12.