Relevance of frailty to mortality associated with the use of antipsychotics among community-residing older adults with impaired cognition

Pharmacoepidemiol Drug Saf. 2018 Mar;27(3):289-298. doi: 10.1002/pds.4385. Epub 2018 Jan 10.

Abstract

Purpose: To examine the association between new antipsychotic use and mortality over 6 months among community-based older adults with cognitive impairment, and variation in risk by frailty and sex.

Methods: We conducted a retrospective cohort study of older (aged 66+) home care clients in Ontario, Canada, using linked administrative health and clinical databases. Included were clients with dementia and/or significant cognitive impairment assessed during April 2008 to March 2013. Frailty was defined using a validated 72-item index. Exposed were those newly dispensed an antipsychotic in the 6 months post cohort entry, with no such claims in the year prior to drug index date. Two-stage matching defined unexposed clients and their index date (matching on age, sex, frailty, assessment year, and propensity score). Outcome was time to death following index date. Cause-specific hazards models were used, and number needed to harm at 6 months was estimated from cumulative incidence function curves.

Results: Among 4955 matched exposed-unexposed pairs, new antipsychotic users showed a significantly increased hazard of mortality at 1, 3, and 6 months relative to unexposed, with the highest risk observed in the first month (hazard ratio [HR] = 2.08 [95% CI, 1.79-2.43]). At 1 month, risk was significantly higher for robust (HR = 3.72 [95% CI, 2.45-5.66]) vs frail (HR = 1.74 [95% CI, 1.40-2.17], P = .002) clients. The number needed to harm was 22.7 and did not vary by frailty but was lower for men (14.9) than for women (35.0).

Conclusions: Risk of antipsychotic-associated mortality was highest in the first month following exposure, varied significantly by client frailty, and was greater among men than among women.

Keywords: antipsychotic; cognitive impairment; frail older adults; home care; mortality; pharmacoepidemiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / adverse effects*
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / mortality*
  • Dementia / drug therapy
  • Dementia / mortality*
  • Female
  • Frail Elderly / statistics & numerical data
  • Frailty / diagnosis
  • Frailty / epidemiology*
  • Geriatric Assessment
  • Home Care Services / statistics & numerical data*
  • Humans
  • Male
  • Off-Label Use / statistics & numerical data
  • Ontario / epidemiology
  • Prevalence
  • Retrospective Studies
  • Risk Factors
  • Sex Factors
  • Survival Rate

Substances

  • Antipsychotic Agents

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