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

Background. Psychotropic medications, in particular second-generation antipsychotics (SGAs) and benzodiazepines, have been associated with harm in elderly populations. Health agencies around the world have issued warnings about the risks of prescribing such medications to frail individuals affected by dementia and current guidelines recommend their use only in cases where the benefits clearly outweigh the risks. This study documents the use of psychotropic medications in the entire elderly population of a Canadian province in the context of current clinical guidelines for the treatment of behavioural disturbances. Methods. Prevalent and incident utilization of antipsychotics, benzodiazepines and related medications (zopiclone and zaleplon) were determined in the population of Manitobans over age 65 in the time period 1997/98 to 2008/09 fiscal years. Comparisons between patients living in the community and those living in personal care (nursing) homes (PCH) were conducted. Influence of sociodemographic characteristics on prescribing was assessed by generalized estimating equations. Non-optimal use was defined as the prescribing of high dose of antipsychotic medications and the use of combination therapy of a benzodiazepine (or zopiclone/zaleplon) with an antipsychotic. A decrease in intensity of use over time and lower proportions of patients treated with antipsychotics at high dose or in combination with benzodiazepines (or zopiclone/zaleplon) was considered a trend toward better prescribing. Multiple regression analysis determined predictors of non-optimal use in the elderly population. Results. A 20-fold greater prevalent utilization of SGAs was observed in PCH-dwelling elderly persons compared to those living in the community. In 2008/09, 27% of PCH-dwelling individuals received a prescription for an SGA. Patient characteristics, such as younger age, male gender, diagnoses of dementia (or use of an acetylcholinesterase inhibitor) or psychosis in the year prior the prescription, were predictors of non-optimal prescribing (e.g., high dose antipsychotics). During the period 2002/3 and 2007/8, amongst new users of SGAs, 10.2% received high doses. Those receiving high dose antipsychotics did not show high levels of polypharmacy. Conclusions. Despite encouraging trends, the use of psychotropic medications remains high in elderly individuals, especially in residents of nursing homes. Clinicians caring for such patients need to carefully assess risks and benefits

Prescription trends of antiseizure medications before and during the COVID-19 pandemic

IntroductionGiven the lack of evidence on how the COVID-19 pandemic impacted antiseizure medication (ASM) use, we examined the trends of ASMs before and during COVID-19.MethodsWe conducted a population-based study using provincial-level health databases from Manitoba, Canada, between 1 June 2016 and 1 March 2021. We used interrupted time series autoregressive models to examine changes in the prevalence and incidence of ASM prescription rates associated with COVID-19 public health restrictions.ResultsAmong prevalent users, the COVID-19 pandemic led to a significant increase in new-generation ASMs with a percentage change of 0.09% (p = 0.03) and a significant decrease in incidence use of all ASMs with a percentage change of −4.35% (p = 0.04). Significant trend changes were observed in the prevalent use of new-generation ASMs (p = 0.04) and incidence use of all (p = 0.04) and new-generation ASMs (p = 0.02). Gabapentin and clonazepam prescriptions contributed 37% of prevalent and 54% of incident use.ConclusionWith the introduction of public health measures during COVID-19, small but significant changes in the incident and prevalent use of ASM prescriptions were observed. Further studies are needed to examine whether barriers to medication access were associated with potential deterioration in seizure control among patients.Conference presentationThe results from this study have been presented as an oral presentation at the 38th ICPE, International Society of Pharmacoepidemiology (ISPE) annual conference in Copenhagen

The Prevalence and Cost of Unapproved Uses of Top-Selling Orphan Drugs

Introduction: The Orphan Drug Act encourages drug development for rare conditions. However, some orphan drugs become top sellers for unclear reasons. We sought to evaluate the extent and cost of approved and unapproved uses of orphan drugs with the highest unit sales. Methods We assessed prescription patterns for four top-selling orphan drugs: lidocaine patch (Lidoderm) approved for post-herpetic neuralgia, modafinil (Provigil) approved for narcolepsy, cinacalcet (Sensipar) approved for hypercalcemia of parathyroid carcinoma, and imatinib (Gleevec) approved for chronic myelogenous leukemia and gastrointestinal stromal tumor. We pooled patient-specific diagnosis and prescription data from two large US state pharmaceutical benefit programs for the elderly. We analyzed the number of new and total patients using each drug and patterns of reimbursement for approved and unapproved uses. For lidocaine patch, we subcategorized approved prescriptions into two subtypes of unapproved uses: neuropathic pain, for which some evidence of efficacy exists, and non-neuropathic pain. Results: We found that prescriptions for lidocaine patch, modafinil, and cinacalcet associated with non-orphan diagnoses rose at substantially higher rates (average monthly increases in number of patients of 14.6, 1.45, and 1.58) than prescriptions associated with their orphan diagnoses (3.12, 0.24, and 0.03, respectively (p75%). Increases in lidocaine patch use for non-neuropathic pain far exceeded neuropathic pain (10.2 vs. 3.6 patients, p<0.001). Discussion In our sample, three of four top-selling orphan drugs were used more commonly for non-orphan indications. These orphan drugs treated common clinical symptoms (pain and fatigue) or laboratory abnormalities. We should continue to monitor orphan drug use after approval to identify products that come to be widely used for non-FDA approved indications, particularly those without adequate evidence of efficacy

Changes in Body Weight and Psychotropic Drugs: A Systematic Synthesis of the Literature

<div><h3>Introduction</h3><p>Psychotropic medication use is associated with weight gain. While there are studies and reviews comparing weight gain for psychotropics within some classes, clinicians frequently use drugs from different classes to treat psychiatric disorders.</p> <h3>Objective</h3><p>To undertake a systematic review of all classes of psychotropics to provide an all encompassing evidence-based tool that would allow clinicians to determine the risks of weight gain in making both intra-class and interclass choices of psychotropics.</p> <h3>Methodology and Results</h3><p>We developed a novel hierarchical search strategy that made use of systematic reviews that were already available. When such evidence was not available we went on to evaluate randomly controlled trials, followed by cohort and other clinical trials, narrative reviews, and, where necessary, clinical opinion and anecdotal evidence. The data from the publication with the highest level of evidence based on our hierarchical classification was presented. Recommendations from an expert panel supplemented the evidence used to rank these drugs within their respective classes. Approximately 9500 articles were identified in our literature search of which 666 citations were retrieved. We were able to rank most of the psychotropics based on the available evidence and recommendations from subject matter experts. There were few discrepancies between published evidence and the expert panel in ranking these drugs.</p> <h3>Conclusion</h3><p>Potential for weight gain is an important consideration in choice of any psychotropic. This tool will help clinicians select psychotropics on a case-by-case basis in order to minimize the impact of weight gain when making both intra-class and interclass choices.</p> </div

Clozapine prescribing in a Canadian outpatient population.

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

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

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.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.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.In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs

Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study.

BackgroundPrenatal antibiotic exposure induces changes in infants' gut microbiota composition and is suggested as a possible contributor in the development of autism spectrum disorders (ASD). In this study, we examined the association between prenatal antibiotic exposure and the risk of ASD.MethodsThis was a population-based cohort study utilizing the Manitoba Population Research Data Repository. The cohort included 214 834 children born in Manitoba, Canada between April 1, 1998 and March 31, 2016. Exposure was defined as having filled one or more antibiotic prescription during pregnancy. The outcome was autism spectrum disorder diagnosis. Multivariable Cox proportional hazards regression was used to estimate the risk of developing ASD in the overall cohort and in a sibling cohort.ResultsOf all subjects, 80 750 (37.6%) were exposed to antibiotics prenatally. During follow-up, 2965 children received an ASD diagnosis. Compared to children who were not exposed to antibiotics prenatally, those who were exposed had a higher risk of ASD: (adjusted HR 1.10 [95% CI 1.01, 1.19]). The association was observed in those exposed to antibiotics in the second or third trimester (HR 1.11 [95% CI 1.01, 1.23] and 1.17 [95% CI 1.06, 1.30], respectively). In the siblings' cohort, ASD risk estimate remained unchanged (adjusted HR 1.08 [95% CI 0.90, 1.30], although it was not statistically significant.ConclusionsPrenatal antibiotic exposure is associated with a small increase in the risk of ASD. Given the potential of residual confounding beyond what it was controlled through our study design and because of possible confounding by indication, such a small risk increase in the population is not expected to be clinically significant

Characteristics and determinants of seasonal influenza vaccination in Manitoba, Canada: A population-wide record-linkage study

Background: Seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba, Canada is consistently low notwithstanding vaccine availability and free-of-charge vaccination. Despite, there is a lack of published evidence on the determinants of uptake of the vaccine. We sought to assess the association between SIV uptake and certain population and primary care physician (PCP) characteristics in Manitoba. Methods: We conducted a longitudinal study utilizing Manitoba administrative health databases. We summarized SIV uptake from 2000/01–2019/20 influenza seasons across subpopulations defined by socioeconomic, health-related and PCP characteristics. Utilizing multivariable generalized estimating equation logistic regression models, we assessed the association between SIV uptake and the socioeconomic, health-related and PCP characteristics, stratified by age group (<5-, 5–17-, 18–44-, 45–64-, ≥65-year-olds) and sex. Results are adjusted odds ratios with associated 95 % confidence intervals. Results: SIV uptake percentage increased over time with 4.4 %, 13.1 %, 17.5 % and 21.7 % of < 5-year-olds, 2 %, 4.9 %, 9.7 % and 13.1 % of 5–17-year-olds, 5.4 %, 8.8 %, 10.7 % and 13.5 % of 18–44-year-olds, 16.8 %, 21.3 %, 23.6 % and 24.6 % of 45–64-year-olds receiving the SIV in 2000–2004, 2005–2009, 2010–2014 and 2015–2019, respectively. There was a decline among ≥ 65-year-olds from 58.5 % to 53.5 %. We observed a similar pattern across subpopulations. There were significantly increased odds of SIV uptake among females within the age groups ≥ 18 years, in higher income quintiles, mostly with increased contact with a PCP/hospitalization within age groups ≥ 18 years, among those who had older or female PCPs (the opposite observation among ≥ 65-year-olds) and whose PCP administered at least one SIV in prior influenza season. These observations were largely consistent irrespective of sex. Conclusion: SIV uptake in Manitoba appears to increase with age, and many socioeconomic, health-related and PCP characteristics appear to be associated with it. These findings may inform targeted vaccination programs to optimize influenza vaccination in Manitoba and similar Canadian jurisdictions

Demographics of patients on clozapine therapy (N=74).

<p>Demographics of patients on clozapine therapy (N=74).</p

Incidence rates of antipsychotic use in the elderly population of Manitoba, 2001–2007.

<p>Incidence rates of antipsychotic use in the elderly population of Manitoba, 2001–2007.</p