Silvia Alessi-Severini

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.

Clozapine: a review of clinical practice guidelines and prescribing trends

BackgroundClozapine effectiveness in the treatment of refractory schizophrenia has been sustained by published evidence in the last two decades, despite the introduction of safer options.DiscussionCurrent clinical practice guidelines have strongly recommended the use of clozapine in treatment-resistant schizophrenia, but prescribing trends do not appear to have followed such recommendations. Clozapine is still underutilized especially in patients at risk of suicide. It seems that physicians are hesitant in prescribing clozapine due to concerns about serious adverse effects. Recent reports have highlighted the need to inform health professionals about the benefits of treating patients with clozapine and have voiced concerns about the underutilization of clozapine especially in patients at risk of suicide.SummaryGuidelines and prescribing patterns reported in various countries worldwide are discussed. Suggestions on how to optimize clozapine utilization have been published but more efforts are needed to properly inform and support prescribers’ practices.

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

Atypical antipsychotics and hyperglycemic emergencies: multicentre, retrospective cohort study of administrative data.

1.7 million in 1996 to

Clozapine prescribing in a Canadian outpatient population.

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.

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

OBJECTIVE To evaluate the relationship between initiation of atypical antipsychotic agents and the risk of hyperglycemic emergencies. METHOD We conducted a multicentre retrospective cohort study using administrative health data from 7 Canadian provinces and the UK Clinical Practice Research Datalink. Hospitalizations for hyperglycemic emergencies (hyperglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic state) were compared between new users of risperidone (reference), and new users of olanzapine, other atypical antipsychotics, and typical antipsychotics. We used propensity scores with inverse probability of treatment weighting and proportional hazard models to estimate the site-specific hazard ratios of hyperglycemic emergencies in the year following drug initiation separately for adults under and over age 66 years. Site-level results were pooled using meta-analytic methods. RESULTS Among 725,489 patients, 55% were aged 66+years; 5% of younger and 19% of older patients had pre-existing diabetes. Hyperglycemic emergencies were rare (1-2 per 1000 person years), but more frequent in patients with pre-existing diabetes (6-12 per 1000 person years). We did not find a significant difference in risk of hyperglycemic emergencies with initiation of olanzapine versus risperidone; however heterogeneity existed between sites. The risk of an event was significantly lower with other atypical (99% quetiapine) compared to risperidone use in older patients [adjusted hazard ratio, 95% confidence interval (CI): 0.69, 0.53-0.90]. CONCLUSIONS Risk for hyperglycemic emergencies is low after initiation of antipsychotics, but patients with pre-existing diabetes may be at greater risk. The risk appeared lower with the use of quetiapine in older patients, but the clinical significance of the findings requires further study.

Cost of shingles: population based burden of disease analysis of herpes zoster and postherpetic neuralgia

Objective Description of demographics of an outpatient population of clozapine users. Methods Retrospective chart review study of an urban population diagnosed with schizophrenia. Assessment of therapeutic histories in relation to clinical practice guidelines. Results Seventy-seven of the 467 patients were on clozapine therapy. Average patients’ age was 39.4 ± 11.8 years) and 68% were males. The majority of patients (68%) had tried 3 or more antipsychotics before switching to clozapine, 21% had tried two and 11% had tried one. Median length of therapy prior to clozapine initiation was 8.9 years in males and 7.7 years in females. Conclusion Until 2010, the use of clozapine was often delayed and more than 2 antipsychotic medications were tried for relatively long periods of time before patients were switched to this effective agent.

Prescribing of psychotropic medications to the elderly population of a Canadian province: a retrospective study using administrative databases

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.

Psychotropic Drug Use before, during, and after Pregnancy: A Population-Based Study in a Canadian Cohort (2001-2013):

BackgroundAround 30% of the population will experience herpes zoster (HZ), 10% of whom develop postherpetic neuralgia (PHN). Together, these illnesses produce a significant economic burden to the healthcare system.MethodsAdministrative healthcare data collected over the period of April 1st 1997 to March 31st 2014 were analyzed to determine the healthcare system burden of HZ using direct medical costs. Episodes of HZ were identified using international classification of disease (ICD) codes. Trends in age-adjusted (AA) HZ-rates were analyzed by piecewise-regression. Total annual and per-episode costs were determined for drug treatment, medical care, and hospitalizations within each year.ResultsThe incidence of HZ increased by 49.5% from 1997/98 to 2013/14. Piecewise-regression of AA-rates revealed a steady AA-rate of 4.7 episodes/1000 person-years (PY) from 1997/98 to a breakpoint in 2008/09, after which rates began to increase reaching 5.7 episodes/1000 PY in 2013/14.Drug costs rose significantly (p <0.03) from

A population-based study of the use of selective serotonin reuptake inhibitors before and after introduction of generic equivalents.

89.77/episode (95% CI: