Do Antipsychotics Hasten Poor Outcomes in Patients with Alzheimer Disease?

Summary and Comment |
August 9, 2013

Do Antipsychotics Hasten Poor Outcomes in Patients with Alzheimer Disease?

  1. Joel Yager, MD

Psychotic symptoms and agitation, not antipsychotic medications per se, were associated with earlier nursing home admission and death.

  1. Joel Yager, MD

Both conventional and atypical antipsychotic medications have been cited as having adverse effects and worsening outcomes in patients with Alzheimer disease (AD). In this NIH-funded study, researchers ascertained the impact of these medications on time to nursing home admission and time to death in 957 patients with mild-to-moderate probable AD between 1983 and 2005.

During follow-up (mean, 4.3 years), 241 patients received antipsychotics (conventional, 138; atypical, 95; both, 8). In analyses that adjusted for demographics, dementia severity, diabetes, hypertension, cardiovascular disease, stroke, extrapyramidal symptoms, and medications for dementia, conventional antipsychotics were associated with earlier nursing home admission than no antipsychotic. After adjustment for psychiatric symptoms (depression, aggression, agitation, psychosis), neither conventional nor atypical antipsychotics were associated with time to admission or with time to death. However, psychosis and agitation were strongly associated with both outcomes.


A meta-analysis of largely institutionalized AD patients (13 of 15 studies) has associated atypical antipsychotics with a small increase in mortality risk, and the FDA has imposed black-box warnings for both conventional and atypical antipsychotics. The meta-analysis's study population may differ in important ways from this group of outpatients. Furthermore, the cognitively and psychiatrically impaired patients in nursing homes are more likely than outpatients to be restrained, an intervention shown to double mortality risk. Mortality risk may vary by agent, with some studies finding higher risks with haloperidol and risperidone; however, numbers in the present study were too small to permit analyses of individual drugs. Before assigning blame to antipsychotic medications, we need to determine whether bad outcomes result from underlying pathological processes and their consequences (e.g., falls, fractures, and head trauma resulting from agitation) or from well-intended treatments.

Editor Disclosures at Time of Publication

  • Disclosures for Joel Yager, MD at time of publication Editorial boards Bulletin of the Menninger Clinic; Eating Disorders: Journal of Treatment and Research; Eating Disorders Review (Editor-in-Chief); Harvard Review of Psychiatry; International Journal of Eating Disorders; UpToDate Leadership positions in professional societies American Psychiatric Association (Chair, Steering Committee and Executive Committee on Practice Guidelines; Co-Chair, DSM5 Clinical and Public Health Committee; Chair, Council on Research and Quality Care)


Reader Comments (2)

Gerard O'Mara FRCPI Physician, Geriatrics, Rural Hospital

At last some evidential (albeit meta-analytical) support for those of us who see large numbers of elderly patients with dementia and behavioural issues. All of the bad press concerning antipsychotics has discouraged their use in an area where quality of life of patients and carers are as least as important as longevity and comorbidity, and where careful introduction of low doses can have dramatic effects.

Chin Tang, Other Healthcare Professional, Geriatrics, nursing facility

well informed

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