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Paula A. Rochon, MD, MPH, FRCPC; Therese A. Stukel, PhD; Kathy Sykora, MSc; Sudeep Gill, MD; Susan Garfinkel, MSc; Geoffrey M. Anderson, MD, PhD; Sharon-Lise T. Normand, PhD; Muhammad Mamdani, PharmD, MA, MPH; Philip E. Lee, MD; Ping Li, PhD; Susan E. Bronskill, PhD; Connie Marras, MD; Jerry H. Gurwitz, MD

Arch Intern Med. 2005;165:1882-1888.

Background  Atypical antipsychotic agents are thought to be less likely than older typical agents to produce parkinsonism. This has not been well documented. We compared the risk of development of incident parkinsonism among older adults dispensed atypical relative to typical antipsychotics.

Methods  Retrospective cohort study of all adults 66 years and older in Ontario. We used Cox proportional hazards models to study the association between the type, potency, and dose of antipsychotic dispensed and the development of parkinsonism during 1 year of follow-up.

Results  All 25 769 older adults prescribed antipsychotics were observed for 11 573 person-years, and 449 events of parkinsonism were identified. Relative to individuals dispensed an atypical antipsychotic, those dispensed a typical agent were 30% more likely (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.58) and those exposed to neither agent were 60% less likely (HR, 0.40; 95% CI, 0.29-0.43) to experience development of parkinsonism. Furthermore, those dispensed lower-potency typical agents were no different (HR, 0.75; 95% CI, 0.48-1.15), and those dispensed higher-potency typical antipsychotics were at close to a 50% greater risk (HR, 1.44; 95% CI, 1.13-1.84) of development of parkinsonism relative to atypical antipsychotics. Relative to those dispensed a high-dose atypical antipsychotic, those dispensed a typical antipsychotic were at similar risk for parkinsonism (Wald ² = 0.14, P = .7).

Conclusions  The risk of development of parkinsonism associated with the use of high-dose atypical antipsychotics was similar to that associated with the use of typical antipsychotics. Caution should be used when prescribing atypical antipsychotic therapy at high doses.

Author Affiliations: Institute for Clinical Evaluative Sciences (Drs Rochon, Stukel, Gill, Anderson, Mamdani, Li, and Bronskill and Mss Sykora and Garfinkel), Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care (Drs Rochon and Lee), Departments of Medicine (Dr Rochon) and Health Policy, Management and Evaluation (Drs Rochon, Stukel, Anderson, and Bronskill), Faculty of Pharmacy (Dr Mamdani), and Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital (Dr Marras), University of Toronto, Toronto, Ontario; Department of Health Care Policy, Harvard Medical School, and Department of Biostatistics, School of Public Health (Dr Normand), Boston, Mass; Meyers Primary Care Institute, University of Massachusetts Medical School, Fallon Foundation, and Fallon Community Health Plan, Worcester (Dr Gurwitz); and Department of Medicine, Queen’s University, Kingston, Ontario (Dr Gill).

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