Colleen J Maxwell1,2, Michael A Campitelli2, David B Hogan3, Christina Diong2, Peter C Austin2,4,5, Joseph E Amuah6, Kate Lapane7, Dallas P Seitz8,9, Sudeep S Gill9,10, Andrea Gruneir2,11, Walter P Wodchis2,4,12, Susan E Bronskill2,4. 1. Schools of Pharmacy and Public Health and Health Systems, University of Waterloo, Waterloo, Canada. 2. Institute for Clinical Evaluative Sciences, Toronto, Canada. 3. Department of Medicine, University of Calgary, Calgary, Canada. 4. Institute of Health Policy, Management, & Evaluation, University of Toronto, Toronto, Canada. 5. Schulich Heart Research Program, Sunnybrook Research Institute, Toronto, Canada. 6. School of Epidemiology, Public Health, and Preventive Medicine, University of Ottawa, Ottawa, Canada. 7. Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA. 8. Division of Geriatric Psychiatry, Queen's University, Kingston, Canada. 9. Providence Care, Kingston, Canada. 10. Department of Medicine, Queen's University, Kingston, Canada. 11. Department of Family Medicine, University of Alberta, Edmonton, Canada. 12. Toronto Rehabilitation Institute, Toronto, Canada.
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.
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.