Association between Antipsychotic Drugs and Mortality in Older Persons with Alzheimer's Disease: A Systematic Review and Meta-Analysis

J Alzheimers Dis. 2016 Mar 31;52(2):631-9. doi: 10.3233/JAD-151207.


Antipsychotic drugs have been inconsistently associated with death risk of Alzheimer's disease (AD) patients. Herein we review and quantitatively summarize the evidence from epidemiological studies. Pertinent studies were identified by searching PubMed and Cochrane Library Register of Controlled Trials through 20 December 2015. The DerSimonian and Laird random effect model was adopted as the pooling method. Twelve studies from nine articles with 11,463 participants were included. The pooled RR of observational studies was 1.36 (95% CI, 0.83-2.24; I2 = 94.9%) for antipsychotic drugs users versus individuals who were not exposed to antipsychotic drugs. When the three studies that were key contributors to the high heterogeneity were excluded, the pooled RR was 2.08 (95% CI 1.39 to 3.13). The result of one double-blind randomized clinical trial indicated that antipsychotic drugs nearly doubled the risk of death in AD patients. In conclusion, there is no evidence of absence of association between antipsychotic drugs' use with death risk of AD patients. Careful assessments of potential benefits and risks should be made before prescribing antipsychotics for treatment of psychosis symptoms and behavioral problems of AD patients.

Keywords: Alzheimer’s disease; antipsychotic agents; epidemiology; meta-analysis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / mortality*
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Humans
  • Risk Factors


  • Antipsychotic Agents