Abstract
BackgroundDespite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine) have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines), particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results.MethodsA population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS) in new users of risperidone compared to new users of FGAs.ResultsAfter controlling for potential confounders (demographics, comorbidity and medication use), risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22–0.67; 0.45, 95% CI: 0.28–0.73; 0.50, 95% CI: 0.33–0.77; 0.65, 95% CI: 0.45–0.94, respectively). At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54–1.05.ConclusionsIn a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.
Highlights
Major physiological changes in the aging body such as variations in body composition, metabolic capacity, and receptor functionality deeply affect the pharmacokinetics and pharmacodynamics of drugs [1,2]
After applying all exclusion criteria a total of 8,885 persons were included in the cohort for analysis: 4,242 persons were in the first-generation agents (FGAs)-exposed group and 4,643 in the risperidone-exposed group (Figure 2)
In both the unadjusted and the adjusted analyses the use of risperidone was associated with a lower risk of extrapyramidal symptoms (EPS) adverse events at 30, 60, 90, and 180 days
Summary
Major physiological changes in the aging body such as variations in body composition, metabolic capacity, and receptor functionality deeply affect the pharmacokinetics and pharmacodynamics of drugs [1,2]. The common presence of multiple comorbid conditions further complicates the management of the elderly patient [1]. Because of these factors elderly subjects have historically been excluded from randomized controlled trials of pharmacotherapy [3]. Medications are often prescribed to older patients despite the limited information available on their safety and effectiveness in the over-65 age group. Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients.
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