Antipsychotics and the Risk of Mortality or Cardiopulmonary Arrest in Hospitalized Adults

J Am Geriatr Soc. 2020 Mar;68(3):544-550. doi: 10.1111/jgs.16246. Epub 2019 Nov 19.


Objectives: Prior studies in outpatient and long-term care settings demonstrated increased risk for sudden death with typical and atypical antipsychotics. To date, no studies have investigated this association in a general hospitalized population. We sought to evaluate the risk of death or nonfatal cardiopulmonary arrest in hospitalized adults exposed to antipsychotics.

Design: Retrospective cohort study.

Setting: Large academic medical center in Boston, Massachusetts.

Participants: All hospitalizations between 2010 and 2016 were eligible for inclusion. We excluded those admitted directly to the intensive care unit (ICU), obstetric and gynecologic or psychiatric services, or with a diagnosis of a psychotic disorder.

Intervention: Typical and atypical antipsychotic administration, defined by pharmacy charges.

Measurements: The primary outcome was death or nonfatal cardiopulmonary arrest during hospitalization (composite).

Results: Of 150 948 hospitalizations in our cohort, there were 691 total events (515 deaths, 176 cardiopulmonary arrests). After controlling for comorbidities, ICU time, demographics, admission type, and other medication exposures, typical antipsychotics were associated with the primary outcome (hazard ratio [HR] = 1.6; 95% confidence interval [CI] = 1.1-2.4; P = .02), whereas atypical antipsychotics were not (HR = 1.1; 95% CI = .8-1.4; P = .5). When focusing on adults age 65 years and older, however, both typical and atypical antipsychotics were associated with increased risk of death or cardiopulmonary arrest (HR = 1.8; 95% CI = 1.1-2.9; and HR = 1.4; 95% CI = 1.1-2.0, respectively). Sensitivity analyses using a propensity score approach and a cohort of only patients with delirium both yielded similar results.

Conclusion: In hospitalized adults, typical antipsychotics were associated with increased mortality or cardiopulmonary arrest, whereas atypical antipsychotics were only associated with increased risk among adults age 65 years and older. Providers should be thoughtful when prescribing antipsychotic medications, especially to older adults in settings where data regarding benefit are lacking. J Am Geriatr Soc 68:544-550, 2020.

Keywords: antipsychotics; mortality; pharmacoepidemiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Boston
  • Delirium* / drug therapy
  • Delirium* / mortality
  • Female
  • Heart Arrest / chemically induced*
  • Heart Arrest / mortality
  • Hospitalization*
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors


  • Antipsychotic Agents