Prescribing and deprescribing guidance for benzodiazepine and benzodiazepine receptor agonist use in adults with depression, anxiety, and insomnia: an international scoping review.

Background: Clinical practice guidelines and guidance documents routinely offer prescribing clinicians' recommendations and instruction on the use of psychotropic drugs for mental illness. We sought to characterise parameters relevant to prescribing and deprescribing of benzodiazepine (BZD) and benzodiazepine receptor agonist (BZRA), in clinical practice guidelines and guidance documents internationally, for adult patients with unipolar depression, anxiety disorders and insomnia to understand similarities and discrepancies between evidence-based expert opinion. Methods: A Scoping Review was conducted to characterize documents that offered evidence-based and/or consensus pharmacologic guidance on the management of unipolar depression, anxiety disorders, obsessive-compulsive disorders, post-traumatic stress disorders and insomnia. A systematic search was conducted of PubMed, SCOPUS, PsycINFO and CINAHL from inception to October 13, 2023 and supplemented by a gray literature search. Documents were screened in Covidence for eligibility. Subsequent data-charting on eligible documents collected information on aspects of both prescribing and deprescribing. Findings: 113 documents offering guidance on BZD/BZRA use were data-charted. Overall, documents gathered were from Asia (n = 11), Europe (n = 34), North America (n = 37), Oceania (n = 7), and South America (n = 4) with the remainder being "International" (n = 20) and not representative to any particular region or country. By condition the documents reviewed covered unipolar depressive disorders (n = 28), anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder (n = 42) and Insomnia (n = 25). Few documents (n = 18) were sufficiently specific and complete to consider as de-prescribing focused documents. Interpretation: Documents were in concordance in terms of BZD and BZRA not being used routinely as first-line pharmacologic agents. When used, it is advisable to restrict their duration to "short-term" use with the most commonly recommended duration being less than four weeks. Documents were less consistent in terms of prescriptive recommendations for specific drug, dosing and administration pattern (i.e regular or 'as needed') selection for each condition. Deprescribing documents were unanimously in favor of gradual dose reduction and patient shared decision-making. However, approaches towards dose-tapering differed substantially. Finally, there were inconsistencies and/or insufficiency of detail, among deprescribing documents, in terms of switching to a long-acting BZD, use of adjunctive pharmacotherapies and micro-tapering. Funding: The authors received no funding for this work.

Resources and interventions to support psychological health and wellbeing in the pharmacy workforce: Analysis and use of a health worker 'burnout' toolkit.

Background: Pharmacists have experienced declines in psychological health and wellbeing post-pandemic. The phenomena of moral distress, disengagement and burnout are associated with workforce attrition, unfitness to practice and inferior quality of patient care. A working group of the Canadian Pharmacists Association (CPhA) was formed to identify resources and interventions (R&I) for occupational psychological health and wellbeing. Objective: To characterize R&I from an evidence-based national health worker 'burnout' Toolkit with potential to support the pharmacy workforce. Methods: All R&I included within a draft 'burnout' Toolkit from the Canadian Health Workforce Network (CHWN) were screened to determine relevancy and usefulness for the pharmacy workforce. R&I with higher grades were data-charted to capture information on topic and content delivery. Final R&I were determined through consensus meetings where 'highly rated' R&I were discussed and selected. Results: Of 140 original CHWN Toolkit R&I, 53 (37.8%) were of potential relevance or usefulness to improve well-being for most in the pharmacy workforce. Of those 53 R&I, 28 (20% of original) were final selections. The majority of R&I at each stage were focused on 'preventing burnout' and 'promoting mental health' (>60%) rather than 'addressing burnout', 'supporting recovery' or managing specific issues in the workplace (i.e. stigma, discrimination, bullying, hostility, workload). No R&I were specifically developed or studied within the pharmacy workforce. Conclusions: Health professions may benefit from the CHWN Toolkit and the knowledge translation activity described here. R&I relevant and useful to the pharmacy workforce generally require adaptation for dissemination and/or implementation. The set of final R&I form the basis for orchestrated plans to support the pharmacy workforce with respect to psychological health and wellbeing. There is a relative lack of R&I devoted to addressing and recovering from burnout and workload management issues.

Risk of long-term benzodiazepine and Z-drug use following the first prescription among community-dwelling adults with anxiety/mood and sleep disorders: a retrospective cohort study.

OBJECTIVE: To measure the incidence of long-term benzodiazepine receptor agonist (BZRA) use among individuals with anxiety, mood and/or sleep disorders. To identify factors associated with long-term use following the first prescription. METHODS: This was a population-based retrospective cohort study using administrative databases in Manitoba, Canada. Individuals with anxiety/mood or sleep disorder who received their first BZRA between 1 April 2001 and 31 March 2015 were included. Long-term use was defined as ≥180 days. Logistic regression modelling was used to examine predictors of long-term use. RESULTS: Among 206 933 individuals included, long-term BZRA use in the first episode of use was 4.5% (≥180 days) following their first prescription. Factors associated with ≥180 days of use included male sex (adjusted OR (aOR) 1.33, 95% CI 1.27 to 1.39), age ≥65 (aOR 5.15, 95% CI 4.81 to 5.52), income assistance (aOR 1.68, 95% CI 1.55 to 1.81), previous non-BZRA psychotropic (aOR 1.93, 95% CI 1.83 to 2.02) or opioid use (aOR 1.16, 95% CI 1.11 to 1.22), high comorbidity (aOR 1.43, 95% CI 1.32 to 1.55), high healthcare use (aOR 1.46, 95% CI 1.33 to 1.60) and psychiatrist prescriber (aOR 2.11, 95% CI 1.93 to 2.32). CONCLUSIONS: Less than 1 in 20 patients use BZRAs ≥180 days in their first treatment episode. Several factors were associated with long-term use following the first prescription and further investigation into whether these factors need to be considered at the point of prescribing is warranted. In light of these findings, future research should examine the predictors of cumulative repeat episodes of BZRA exposure.

Medication review service implementation in community pharmacy settings: Scoping review with focus on implementation studies.

BACKGROUND: Medication reviews are a structured clinical intervention with the general goals of improving patient drug knowledge and detecting and resolving drug-related problems in an individual patient's medication regimen. A variety of barriers entrenched in the traditional drug distribution and dispensing model of pharmacy business has continued to challenge the implementation efforts of medication review services worldwide in the community pharmacy setting. MAIN OBJECTIVES: i) Characterize original research studies that sought to enhance medication review service implementation in community pharmacy settings. ii) Categorize the broader corpus of scientific literature (beyond original implementation studies) on medication review service implementation in community pharmacy settings. METHODS: A broad systematic search strategy was applied to ovid MEDLINE, Embase, CINAHL and Cochrane Library to create an over-arching view and extensively ordered bibliography of the diverse research publication types dealing with the topic of medication review service implementation in the community pharmacy setting. A scoping review was subsequently conducted on original research studies that utilized various strategies to enhance the implementation of this service in community pharmacies. Data-charting evaluated the location of implementation studies, the strategies undertaken, the scale of implementation strategies, the use of DII (Dissemination, Implementation and Improvement) science theory, sample sizes, and DII outcomes. RESULTS: Of 5947 records screened, 419 fulfilled the inclusion criteria (from abstract screening) to be deemed suitable for categorization and inclusion into the broader survey on this topic. Of these 419 publications, only 75 were original research specifically focused on enhancing the implementation of medication reviews in community pharmacy. A large majority of the publications were qualitative studies (n = 203). The remaining articles were improvement studies (n = 36), descriptive observational studies (n = 49), reviews (n = 69) and methodology papers (n = 16). Twenty-nine of these articles were deemed suitable for inclusion in more than one category. After full-text screening, 41 of the 75 implementation publications, representing 40 original studies, published between 1999 and 2019, were eligible for data-charting. The majority of these studies occurred in North America (n = 30), used some form of education as the most common implementation strategy (n = 22) and measured 'adoption' (extent or frequency of medication reviews delivered) most frequently as an implementation outcome (n = 30). Just over half of the studies used a multi-faceted implementation strategy (n = 21). Only 9 studies used a theory, model or framework at any point in the research process to test hypotheses or explain empirical findings. CONCLUSIONS: There is an abundance of publications addressing various issues surrounding medication review implementation in community pharmacies. However, the literature appears disproportionately represented by qualitative studies. There is also a need for more rigorously conducted implementation studies on medication review services in community pharmacy.

Novel Measures of Benzodiazepine and Z-Drug Utilisation Trends in a Canadian Provincial Adult Population (2001-2016).

PURPOSE: 1) To evaluate trends for benzodiazepines (BZD) and Z-Drugs over 15-years in a general Canadian adult population measured by: a) consumption b) pharmacologic exposure c) dose intensity and d) prevalence of use. 2) To demonstrate the utility of Diazepam Milligram Equivalence (DME) based measurements when used in conjunction with traditional standard measurements of drug utilization such as the Defined Daily Dose (DDD) system. METHODS: Administrative data covering all prescriptions from April 2001-March 2016 for BZD and Z-Drugs for patients ≥18 years was used. Consumption was calculated as DDD/1000-person days. Dose intensity (DI) was determined by conversion of individual daily doses to Diazepam Milligram Equivalents (DME). Pharmacologic exposure (PE) was calculated as DME-DDD/1000-person days. Prevalence was determined as the proportion of the adult population with receipt of ≥1 prescription in a given year. Changes were assessed using either Poisson or simple linear regression at an alpha of 0.05. RESULTS: Z-Drug usage (~99% zopiclone) statistically increased on every measure over the course of the study period; consumption (8.2 to 28.6 DDD/1000-person days), PE (4.1 to 14.3 DME-DDD/1000-person days), DI (5.0 to 5.43 DME/day) and prevalence (2.0% to 4.8%). For BZD the only statistically significant changes were in DI (17.1 to 20.1 DME/day) and prevalence (9.3% to 8.1%). Consumption and PE gradually increased from 2001 to 2011 for BZD before declining thus producing a non-significant trend for BZD. CONCLUSION: 1) Z-Drug usage increased markedly from 2001 to 2016 whereas BZD use only increased in terms of DI. 2) DME-based measurements enable further interpretation of BZD utilization compared to sole reliance on DDD.

Prescription drug coverage in Canada: a review of the economic, policy and political considerations for universal pharmacare.

BACKGROUND: Canadians have long been proud of their universal health insurance system, which publicly funds the cost of physician visits and hospitalizations at the point of care. Prescription drugs however, have been subject to a patchwork of public and private coverage which is frequently inefficient and creates access barriers to necessary medicine for many Canadians. METHODS: A narrative review was undertaken to understand the important economic, policy and political considerations regarding implementation of universal prescription drug access in Canada (pan-Canadian pharmacare). PubMed, SCOPUS and google scholar were searched for relevant citations. Citation trails were followed for additional information sources. Published books, public reports, press releases, policy papers, government webpages and other forms of gray literature were collected from iterative internet searches to provide a complete view of the current state on this topic. MAIN FINDINGS: Regarding health economics, all five of the reviewed pharmacare simulation models have shown reductions in annual prescription drug expenditure. However, differing policy and cost assumptions have resulted in a wide range of cost-saving estimates between models. In terms of policy, a single-payer, 'first-dollar' coverage model, using a minimum national formulary, is the model most frequently advocated by the academic community, healthcare professions and many public and patient groups. In contrast, a multi-payer, catastrophic 'last-dollar' coverage model, more similar to the current "patchwork" state of public and private coverage, is preferred by industry drug manufacturers and private health insurance companies. Primary concerns from the detractors of universal, single-payer, 'first-dollar' coverage are the financing required for its implementation and the access barriers that may be created for certain patient populations that are not majorly present in the current public-private payer mix. CONCLUSION: Canada patiently awaits to see how the issue of prescription drug coverage will be resolved through the work of the Advisory Council on the Implementation of National Pharmacare. The overarching and ongoing discourse on policy and program implementation may be construed as a political debate informed by divergent public and private interests.

Translating Benzodiazepine Utilization Data into Meaningful Population Exposure: Integration of Two Metrics for Improved Reporting.

Drug utilization research on benzodiazepines remains important for measuring trends in consumption within and across borders over time for the sake of monitoring prescribing patterns and identifying potential population safety concerns. The defined daily dose (DDD) system by the World Health Organization (WHO) remains the internationally accepted standard for measuring drug consumption; however, beyond consumption, DDD-based results are difficult to interpret when individual agents are compared with one another or are pooled into a total class-based estimate. The diazepam milligram equivalent (DME) system provides approximate conversions between benzodiazepines and Z-drugs (i.e. zopiclone, zolpidem, zaleplon) based on their pharmacologic potency. Despite this, conversion of total dispensed benzodiazepine quantities into DME values retains diazepam milligrams as the total unit of measurement, which is also impractical for population-level interpretation. In this paper, we propose the use of an integrated DME-DDD metric to obviate the limitations encountered when the component metrics are used in isolation. Through a case example, we demonstrate significant change in results between the DDD and DME-DDD method. Unlike the DDD method, the integrated DME-DDD metric offers estimation of population pharmacologic exposure, and enables superior interpretation of drug utilization results, especially for drug class summary reporting.

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research.

Various adverse events resulting from, or associated with, benzodiazepine and/or Z-drug use have been extensively reported on and discussed in great detail within the biomedical literature. It is widely accepted that motor vehicle accidents and falls leading to fractures in older adults are major adverse events that have been shown to occur more frequently in users of sedative-hypnotic medication, especially of the benzodiazepine and related Z-drug variety. However, the last few years have seen increasing reports in the literature raising the issue of benzodiazepine and Z-drug exposure in the development of other serious medical issues including dementia, infections, respiratory disease exacerbation, pancreatitis, and cancer. This article provides an overview and interpretation on the current state of evidence regarding each of these associations and proposes what gaps in the evidence for drug-exposure-harm associations need to be addressed in the future for the purpose of evaluating causality of harm as it relates to these drugs.