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

Maxwell CJ, Campitelli MA, Hogan DB, Diong C, Austin PC, Amuah JE, Lapane K, Seitz DP, Gill SS, Gruneir A, Wodchis WP, Bronskil SE. Pharmacoepidemiol Drug Saf. 2018; 27(3):289-98. Epub 2018 Jan 10.

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.