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 chi(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.

OBJECTIVE: To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics. DESIGN: Population based retrospective cohort study. SETTING: Ontario, Canada. Patients 32,710 older adults (< or = 65 years) with dementia (17,845 dispensed an atypical antipsychotic and 14,865 dispensed a typical antipsychotic). MAIN OUTCOME MEASURES: Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient's admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended. RESULTS: After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. CONCLUSION: Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics.

OBJECTIVE: To evaluate the dose-related benefit of angiotensin-converting enzyme (ACE) inhibitor therapy among older adults with heart failure and to evaluate whether low-dose ACE inhibitor therapy is better than none. DESIGN: Observational cohort study. SETTING: Community-dwelling older adults in Ontario, Canada. PATIENTS/PARTICIPANTS: We identified 16539 adults 66 years or older who survived 45 days following their first heart failure hospitalization discharge. MEASUREMENT AND MAIN RESULTS: Multivariate techniques including propensity scores were used to study the association between the dose of ACE inhibitor therapy dispensed and 3 outcomes: survival, survival or heart failure rehospitalization, and survival or all-cause hospitalization at 1 year of follow-up. Logistic regression models explored the association between initial dose dispensed and subsequent dose reduction or drug cessation. Overall, 10793 (65.3%) of patients were dispensed ACE inhibitor therapy, with more than a third (3935; 36.5%) initiated on low-dose therapy. Relative to dispensing of low-dose ACE inhibitor therapy, nonuse was associated with increased mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.02 to 1.22). Dispensing medium-dose therapy provided a benefit similar to low-dose (HR, 0.94; CI, 0.86 to 1.03) and dispensing of high-dose therapy was associated with improved survival benefit (HR, 0.76; CI, 0.68 to 0.85). Relative to dispensing of low-dose ACE inhibitor therapy, dispensing high-dose conferred a benefit (HR, 0.87; CI, 0.80 to 0.95) on the composite outcome of 1-year mortality or heart failure hospitalization and the composite outcome of 1-year mortality or all-cause hospitalization (HR, 0.87; CI, 0.81 to 0.93). Relative to those dispensed low-dose ACE inhibitor therapy, those initially dispensed high-dose therapy were twice as likely to have their subsequent dose reduced or the therapy discontinued (odds ratio, 2.36; CI, 2.07 to 2.69). CONCLUSION: Our findings suggest that when possible, older adults should be titrated to the higher doses of ACE inhibitor therapy evaluated in clinical trials. If older adults cannot tolerate higher doses, then low-dose ACE inhibitor therapy is superior to none. High-dose ACE inhibitor therapy is not as well tolerated as lower doses.

OBJECTIVES: To compare patterns of potentially inappropriate drug therapy prescribing in community-dwelling older adults and nursing home residents in Ontario, Canada. DESIGN: A retrospective cohort study using administrative databases. SETTING: Ontario community and nursing home facilities. PARTICIPANTS: All 1,275,619 older adults aged 66 and older in Ontario (1,216,900 community-dwelling and 58,719 nursing home residents) who were dispensed at least one prescription from the comprehensive provincial drug plan in 2001. In Ontario, the provision of clinical pharmacy services is mandated in the nursing home setting. No comparable program exists for older adults in the community setting. MEASUREMENTS: Potentially inappropriate drug prescribing was compared between community-dwelling and nursing home residents in two categories: those to always avoid and therapies considered rarely appropriate to prescribe. RESULTS: Of the 1,275,619 adults in the cohort, nursing home residents were older (mean age+/-standard deviation=84.2+/-7.6 vs 75.0+/-6.5, P<.001), included more women (73.3% vs 57.7%, P<.001), had higher comorbidity scores (measured by the number of distinct drug therapies dispensed in the prior year (10.7+/-6.8 vs 7.2+/-5.7, P<.001) and Charlson comorbidity scores (1.4+/-1.6 vs 0.9+/-1.5, P<.001)) than community-dwelling individuals. Community-dwelling older adults were significantly more likely to be dispensed at least one drug therapy in the always avoid or rarely appropriate category than nursing home residents (3.3% vs 2.3%, P<.001). Using a logistic regression model that controlled for age, sex, and comorbidity (number of distinct drug therapies dispensed in the prior year), nursing home residents were close to half as likely to be dispensed one of these potentially inappropriate drug therapies as community-dwelling older adults (odds ratio=0.52, 95% confidence interval=0.49-0.55, P<.001). CONCLUSION: Potentially inappropriate drug therapy in the always avoid and rarely indicated categories is dispensed less often to nursing home residents than to older community-dwelling adults. Clinical pharmacist services, which are mandated in the nursing home setting, may be responsible for these differences in Ontario, Canada.

OBJECTIVE: To explore the prescribing of potentially inappropriate drug therapy in Ontario, Canada where there is a restrictive drug formulary relative to the US where there is no single drug formulary. METHODS: A retrospective, cohort study using an administrative database (Ontario, Canada) compared with published survey results (US). All 1,088,680 community-dwelling adults >or=66 years of age in Ontario, Canada compared with published survey results from 2455 community-dwelling older adults in the US in 1996.Patterns of potentially inappropriate drug prescribing were compared between countries using a list of 33 potentially inappropriate drug therapies. These therapies were classified by an expert panel into three categories: (i) those to always avoid; (ii) those which are rarely appropriate; and (iii) those with only some indications to prescribe. RESULTS: Among the 33 potentially inappropriate drug therapies, 15 (45%) prescribed in the US were not available through Ontario's drug formulary. Potentially inappropriate drug therapies available through the Ontario Drug Benefit Plan (ODB) and also in the US were frequently prescribed in both Ontario and the US. Differences in prescribing patterns of individual drug therapies were noted between the two countries. Specifically, in the rarely appropriate category, diazepam, a long half-life benzodiazepine, was much more frequently dispensed in Ontario than in the US (3.18% vs 1.37%). In contrast, dextropropoxyphene, an opioid with a poor adverse event profile was more frequently prescribed in the US than in Ontario (6.21% vs 0.74%). CONCLUSION: Almost half of the potentially inappropriate drug therapies that are available in the US are unavailable from Ontario's drug formulary. Potentially inappropriate drug therapies that were available through the ODB were frequently prescribed in both countries. Alternative approaches that make information immediately accessible to physicians at the time they make prescribing decisions should be considered to improve prescribing practices.