Potential causes of higher mortality in elderly users of conventional and atypical antipsychotic medications

J Am Geriatr Soc. 2008 Sep;56(9):1644-50. doi: 10.1111/j.1532-5415.2008.01839.x. Epub 2008 Aug 4.


Objectives: To investigate the potential mechanisms through which conventional antipsychotic medication (APM) might act, the specific causes of death in elderly patients newly started on conventional APM were compared with those of patients taking atypical APM.

Design: Cohort study.

Setting: Community.

Participants: All British Columbia residents aged 65 and older who initiated a conventional or atypical APM between 1996 and 2004.

Measurements: Cox proportional hazards models were used to compare risks of developing a specific cause of death within 180 days of APM initiation. Potential confounders were adjusted for using traditional multivariable, propensity-score, and instrumental-variable adjustments.

Results: The study cohort included 12,882 initiators of conventional APM and 24,359 initiators of atypical APM. Of 3,821 total deaths within the first 180 day of use, cardiovascular (CV) deaths accounted for 49% of deaths. Initiators of conventional APM had a significantly higher adjusted risk of all CV death (hazard ratio (HR)=1.23, 95% confidence interval (CI)=1.10-1.36) and out-of-hospital CV death (HR=1.36, 95% CI=1.19-1.56) than initiators of atypical APM. Initiators of conventional APM also had a higher risk of death due to respiratory diseases, nervous system diseases, and other causes.

Conclusion: These data suggest that greater risk of CV deaths might explain approximately half of the excess mortality in initiators of conventional APM. The risk of death due to respiratory causes was also significantly higher in conventional APM use.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / mortality
  • Antipsychotic Agents / therapeutic use
  • Antipsychotic Agents / toxicity*
  • British Columbia
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / mortality
  • Cause of Death*
  • Cohort Studies
  • Comorbidity
  • Cross-Sectional Studies
  • Delirium / drug therapy
  • Delirium / mortality
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Mood Disorders / drug therapy
  • Mood Disorders / mortality
  • Nervous System Diseases / chemically induced
  • Nervous System Diseases / mortality
  • Probability
  • Proportional Hazards Models
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / mortality
  • Respiratory Tract Diseases / chemically induced
  • Respiratory Tract Diseases / mortality
  • Risk Factors


  • Antipsychotic Agents