Movement Disorders in Children and Adolescents Receiving Antipsychotic Pharmacotherapy: A Population-Based Study.

OBJECTIVES: To describe a cohort of young users of risperidone and quetiapine in the province of Manitoba (Canada) and assess the risk for movement disorders in the two treatments. METHODS: This was a population-based study conducted on all residents of the province of 19 years of age and younger who received prescriptions for risperidone or quetiapine between April 1, 1996, and March 31, 2011. Incident rates of antipsychotic use were reported. The risk for movement disorders in patients treated with quetiapine compared with those treated with risperidone was assessed by time-to-event analysis using Cox proportional hazards models. RESULTS: Between April 1, 1996, and March 31, 2011, 23,888 youth (age ≤19 years) were prescribed an antipsychotic agent. Among them, 8756 were identified as new incident users. After applying exclusion criteria, 2594 individuals comprised the cohort of users of risperidone and quetiapine. The use of quetiapine was associated with a lower risk of extrapyramidal symptoms (EPSs) adverse events. The unadjusted and adjusted hazard ratios (95% confidence interval [CI]) for quetiapine versus risperidone were 0.83 (0.56-1.25) and 0.53 (0.34-0.83), respectively. CONCLUSION: EPS diagnoses have been detected in children treated with quetiapine; however, the risk of movement disorders appears to be higher with treatment with risperidone. Clinicians should always take into consideration the risk-benefit before treating children with antipsychotic medications and should be vigilant of the onset of drug-induced adverse events.

Movement disorders in elderly users of risperidone and first generation antipsychotic agents: a Canadian population-based study.

BACKGROUND: Despite 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. METHODS: A 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. RESULTS: After 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. CONCLUSIONS: In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.

Adverse events in elderly users of antipsychotic pharmacotherapy in the province of Manitoba: a retrospective cohort study.

BACKGROUND: Antipsychotic medications have been widely used in elderly patients for treatment of a variety of diagnoses. The aim of our study was to compare the incidence of cerebrovascular and cardiac events as well as mortality in elderly persons treated with second-generation antipsychotics (SGAs) with that of elderly persons treated with conventional first-generation agents (FGAs) in the province of Manitoba. METHODS: A population-based retrospective cohort study of all residents of Manitoba aged 65 and older, who were dispensed antipsychotic medications for the first time during the period from April 1, 2000, to March 31, 2007, was conducted using Manitoba Health administrative databases. Cox proportional hazards models were used to compare risks of adverse events in FGA and SGA users. RESULTS: After controlling for potential confounders (demographics, comorbidity, and medication use), SGA use was not associated with a significantly greater risk of cerebrovascular events, cardiac arrhythmia, and congestive heart failure compared to FGA use (adjusted hazard ratios [HR], respectively: 1.136; 95% CI, 0.961-1.344; 0.865; 95% CI, 0.336-2.232; 1.127, 95% CI, 0.902-1.409). Second-generation antipsychotics users were found to be at a lower risk of mortality (adjusted HR, 0.683; 95% CI, 0.577-0.809), but at a higher risk of myocardial infarction (adjusted HR, 1.614; 95% CI, 1.024-2.543) compared to FGA users. CONCLUSIONS: Among elderly users of antipsychotic medications, the risk of cerebrovascular events, cardiac arrhythmia, and congestive heart failure was similar in FGA and SGA users. Whereas SGA users were at a higher risk of nonfatal myocardial infarction, the use of FGAs was associated with an increased risk of death. Antipsychotic pharmacotherapy in older persons needs to be chosen with careful consideration of all risks and benefits.

Ten years of antipsychotic prescribing to children: a Canadian population-based study.

OBJECTIVE: To report the prescribing of antipsychotics to the youth population of the Canadian province of Manitoba during the course of a decade. METHODS: Use of antipsychotics in children and adolescents (aged 18 years or younger) was described using data collected from the administrative health databases of Manitoba Health and the Statistics Canada census between the fiscal years of 1999 and 2008. RESULTS: The prevalence of antipsychotic use in this segment of the population increased with the introduction of the second-generation antipsychotics (SGAs) from 1.9 per 1000 in 1999 to 7.4 per 1000 in 2008. The male-to-female antipsychotic usage ratio increased from 1.9 to 2.7 as the male youth population represented the fastest-growing subgroup of antipsychotic users in the entire population of Manitoba. The total number of prescriptions also increased significantly despite the lack of approved indications in this population. Proportion of use remained equally split between high- and low-income users. More than 70% of antipsychotic prescriptions to children and adolescents were written by general practitioners. The most common diagnoses linked to antipsychotic use were attention-deficit hyperactivity disorder and conduct disorders. Use of antipsychotics in combination with methylphenidate increased from 13% to 43%. CONCLUSION: Extensive off-label use of SGAs has been observed in the youth population of Manitoba for treatment of aggressive behaviours across a range of diagnoses. It is important to monitor antipsychotic prescribing to children as more reports of significant adverse events associated with antipsychotics become available.

Utilization and costs of antipsychotic agents: a Canadian population-based study, 1996-2006.

OBJECTIVE: This study evaluated the prescribing patterns and costs for antipsychotic agents in the population of the Canadian province of Manitoba over the past decade. METHODS: A population-based study of antipsychotic utilization and costs was conducted on data collected from the administrative databases of the Manitoba Population Health Data Repository and the Statistics Canada census between index years 1996 and 2006 (April 1, 1995, through March 31, 2006). RESULTS: The total annual number of antipsychotic prescriptions dispensed in Manitoba increased by 227% between 1996 and 2006, and the prevalence of antipsychotic users increased by 62% over the same time interval. The fastest-growing segment of antipsychotic users in Manitoba appears to be young males, who increased from .16% in 1996 to .88% in 2006. The highest numbers of prescriptions were reported for schizophrenia, dementia, and conduct disorder. Annual expenditures for antipsychotics increased from $1.7 million in 1996 to $22.0 million in 2006 (expenditures are in Canadian dollars). The cost of second-generation agents reached 80% of total antipsychotic expenditures in 2006; risperidone was the most prescribed agent in all age groups of patients. The per-patient annual cost of antipsychotic pharmacotherapy increased by approximately 680% between 1996 and 2006 in Manitoba. CONCLUSIONS: The number of antipsychotic prescriptions and the prevalence of users of antipsychotic medications increased significantly in Manitoba over the study period, despite a steady-state population of approximately 1.2 million. Incremental costs relative to the use of antipsychotic medications can be explained by the market penetration of the second-generation agents and their expanded use in the treatment of various diagnoses.