Use Of Benzodiazepine Receptor Agonists Research Articles

“People should be allowed to taper at their own pace...”: A content analysis of free-text responses to a questionnaire on discontinuing long-term benzodiazepine receptor agonist use

Abstract Introduction Interventions are needed to support discontinuation of long-term use (≥3 months) of benzodiazepine receptor agonists (BZRAs) which persists in healthcare settings worldwide.[1] A theory-based questionnaire was developed to examine mediators of behaviour change relating to discontinuing long-term BZRA use.[2] Aim To examine free-text responses to an online questionnaire on barriers and facilitators to discontinuing long-term BZRA use. Methods The questionnaire was disseminated via online BZRA support groups to community-based adults with either current or previous experience of long-term BZRA use. All respondents self-declared that they met the eligibility criteria: ≥ 18 years, current or previous experience of long-term BZRA use (≥ 3months), and living in the community (i.e. not based in inpatient treatment settings). There were no exclusion criteria based on geographical location or the use of other medications. The questionnaire included four free-text questions which elicited detailed insights into respondents’ experiences of long-term BZRA use. These free-text questions focused on: (1) barriers and (2) facilitators to discontinuing BZRA use, (3) additional supports required to discontinue BZRA use, and (4) additional comments regarding BZRA use. The total sample size was calculated based on the number of individuals that clicked on the questionnaire. This was used as an indicator of the number of individuals that saw the questionnaire and provided a baseline sample size in order to calculate the response rate from the number of completed questionnaires. Response data were analysed using content analysis. Experts by experience with previous experience of long-term BZRA use were involved in developing the questionnaire and reviewing the results. Results The overall response rate was 46.2% (271/587). The majority of respondents were female (77%, n=208) and the median age was 52 years (range 19-81 years). Most respondents resided in the United States (69%, n=185), Canada (8%, n=23) or United Kingdom (8%, n=21) and were first prescribed BZRAs by a general practitioner (45%, n=118) or psychiatrist (41%, n=112). Almost half of respondents (49%, n= 134) had been taking BZRAs for over 10 years and the main reported reason for their initial BZRA prescription was anxiety (52%, n=141). Most respondents (68%, n=185) had previously attempted to discontinue BZRAs and 82% (n=223) reported that they were tapering from BZRAs at the time of completing the questionnaire. The most commonly reported barrier to BZRA discontinuation related to the consequences of stopping the medication, including withdrawal symptoms and the possibility of the original symptoms returning. The most common facilitator that respondents reported would help them in discontinuing BZRA use was support, primarily from medical professionals. Many respondents reported having been harmed or negatively affected in some way because of BZRA use. Several respondents expressed regret over ever taking BZRAs and/or reported that, with the benefit of hindsight, they should never have taken BZRAs in the first instance. Conclusion The findings highlight the range of barriers faced by those attempting BZRA discontinuation and the importance of additional supports. Holistic and person-centred approaches are needed to support discontinuation of long-term BZRA use that considers an individual’s personal circumstances and wider social context.

0739 Does Benzodiazepine Receptor Agonist Use, Insomnia, and OSA Explain Variation in Cognitive Performance?

0739 Does Benzodiazepine Receptor Agonist Use, Insomnia, and OSA Explain Variation in Cognitive Performance?

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

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. 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. 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. 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. The authors received no funding for this work.

‘We need more support and doctors that understand the process of tapering …’: A content analysis of free‐text responses to a questionnaire on discontinuing long‐term benzodiazepine receptor agonist use

AbstractBackgroundMany individuals worldwide continue to take benzodiazepine receptor agonists (BZRAs) long term (≥3 months). The aim of this study was to conduct a content analysis of the views and experiences of discontinuing long‐term BZRA use as documented in the free‐text responses of respondents to an online questionnaire examining mediators of behaviour change relating to the discontinuation of long‐term BZRA use.DesignThe questionnaire was disseminated via online BZRA support groups to community‐based adults with either current or previous experience of long‐term BZRA use. The four free‐text questions focused on (1) barriers and (2) facilitators to discontinuing BZRA use; (3) additional supports required to discontinue BZRA use; and (4) additional comments regarding BZRA use. Response data were analysed using summative content analysis.ResultsThe most commonly reported barrier to BZRA discontinuation related to the consequences of stopping the medication, including withdrawal symptoms and the possibility of return of the original symptoms. The most common facilitator that respondents reported would help them in discontinuing BZRA use was support, primarily from medical professionals. Many respondents reported having been harmed or negatively affected in some way because of BZRA use. Several respondents expressed regret over ever taking BZRAs and/or reported that, with the benefit of hindsight, they should never have taken BZRAs in the first instance.ConclusionThe findings highlight the range of barriers faced by those attempting BZRA discontinuation and the importance of additional supports. Holistic and person‐centred approaches are needed to support discontinuation of long‐term BZRA use that considers an individual's personal circumstances and wider social context.Patient or Public Contribution‘Experts by experience’ with previous experience of long‐term BZRA use were involved in developing the questionnaire and writing the manuscript as collaborators. Individuals with lived experience of taking BZRAs completed the questionnaire.

Development and validation of a theory-based questionnaire examining barriers and facilitators to discontinuing long-term benzodiazepine receptor agonist use

BackgroundLong-term use of benzodiazepine receptor agonists (BZRAs) is a persistent healthcare challenge and poses patient safety risks. Interventions underpinned by behaviour change theory are needed to support discontinuation of long-term BZRA use. The aim of this study was to develop and validate a questionnaire based on the Theoretical Domains Framework (TDF) to examine mediators of behaviour change relating to the discontinuation of long-term BZRA use. MethodsAn initial 52 item questionnaire was developed using the 14 domains of TDF version 2 and iteratively refined over two rounds. The questionnaire was disseminated online via online support groups that focused on BZRAs to community-based adults with either current or previous experience of taking BZRAs on a long-term basis (≥3 months). Confirmatory factor analysis was undertaken to assess the questionnaire's reliability, discriminant validity and goodness of fit. The Standardized Root Mean Square Residual (SRMR), Root Mean Square Error of Approximation (RMSEA) and Comparative Fit Index (CFI) were calculated. ResultsFollowing an iterative process of adjustment, the results obtained from confirmatory factor analysis resulted in the final questionnaire consisting of 29 items across nine theoretical domains. The internal consistency reliability values across these domains ranged from 0.62 to 0.85. For the final model, the SRMR was 0.23, the RMSEA was 0.11 and the CFI was 0.6. ConclusionsThe questionnaire offers a potential tool that could be used to identify domains that need to be targeted as part of a behaviour change intervention at an individual patient level. Further research is needed to assess the questionnaire's acceptability and usability, and to develop a scoring system so that domains can be prioritised and subsequently targeted as part of an intervention.

Reducing long-term use of benzodiazepine receptor agonists: In-depth interview study with primary care stakeholders.

To increase our understanding of which factors contribute to long-term benzodiazepine receptor agonist (BZRA) use for insomnia in primary care, from a patients', general practitioners' (GP) and pharmacists' perspective. Qualitative research following a grounded theory approach. Primary care in Belgium. Twenty-four participants were interviewed, including nine patients, six GPs and nine pharmacists. In-depth, semistructured interviews with iterative cycles of data collection and analysis. Transcripts were analysed using the framework method. Thematic findings were interpreted in the context of the Theoretical Domains Framework. A reflexive relation was identified between views about hypnotic use at the level of society, healthcare and patients. Behaviour change appeared to depend strongly on context and social influence, including a need for supporting relationships by all stakeholders. Six key messages captured factors that contribute to long-term BZRA use for insomnia in primary care: societal beliefs as a game changer, the opportunity of nonpharmacological treatment, collaborative primary care, patient-centred goals, informed consent and self-management. Long-term BZRA use for insomnia is a complex and multifaceted public health problem that is not adequately addressed in primary care at this time. Although primary care professionals in this study found discontinuation of long-term BZRA use relevant to the patient's health, many organisational and personal barriers were reported. Moreover, the current social and healthcare context is not empowering patients and professionals to reduce long-term BZRA use for insomnia. Specifically, for primary care, all stakeholders reported the need for a nonmedicalised relationship between the patient and GP to lower prescribing rates. The Flemish Patient Platform, a patient representative organisation, assisted with recruitment by launching a call for participants in their newsletter and volunteered to disseminate the results. The call for recruitment was also published online in social media groups regarding insomnia and via posters in public pharmacies. Patients or public were not involved in designing or conducting the interview study.

Trends in the use of benzodiazepine receptor agonists among working-age adults in Belgium from 2004 to 2018.

The use of psychotropics, such as benzodiazepine receptor agonists (BzRAs), among working-age adults in Belgium has shown educational differences. However, it is unclear how work status plays a role in this relationship. Therefore, this research aims to investigate whether work status explains observed educational differences in BzRA use. In addition, considering medicalisation processes, where non-medical factors, such as work status, are increasingly associated with medical mental health care-seeking behavior, this research also aims to investigate whether work status explains observed educational differences in BzRA use, regardless of mental health status. Data are obtained from the Belgian Health Interview Survey (BHIS). Four successive waves are covered: 2004, 2008, 2013, and 2018. The weighted data represent a sample of 18,547 Belgian respondents aged 18 to 65 years old. Poisson regression models are used to analyze the research aims. Time evolutions are plotted using marginal means postestimation. The average use of BzRAs shows a slight decline over the waves studied (2004 = 5.99, 2008 = 5.88, 2013 = 5.33, 2018 = 4.31). Educational and work status differences in BzRA use are observed, regardless of mental health status. Individuals with longer education report lower use compared to individuals with shorter education, and individuals who are unemployed, (pre-)retired, or sick or disabled report higher use compared to employed individuals. Furthermore, work status acts as a mediator, partially explaining educational differences in BzRA use, regardless of mental health status. Work-related uncertainty leads to increased prescribing and medication use, regardless of mental health. Medicalisation and pharmaceuticalisation processes detach social problems from their social roots and treat them as personal failures. The marginalization of the social roots of unemployment, sick leave and involuntary (pre-)retirement has led to a personalization of responsibility. Negative feelings arising from such work statuses may cause isolated, non-specific symptoms for which medical treatment is sought.

“At the time I only wanted to relieve stress”: Exploring motivation for behaviour change in long-term hypnotic users

BackgroundMotivating patients to discontinue long-term benzodiazepine receptor agonist (BZRA) use for insomnia remains an important challenge in primary care because of the medication's unfavourable risk-benefit profile. Previous studies have shown that understanding the complexity of patients' motivation is crucial to the primary care physician for providing effective interventions efficiently. Theoretical frameworks about behaviour change show that motivation is a multi-layered concept that interacts with other concepts, which aligns with a holistic perspective or implementation of the biopsychosocial model. AimExploring primary care patients’ views and ideas on what factors helped or hindered them in discontinuing long-term BZRA use, in relation to motivation as conceptualised in the Behaviour Change Wheel, and associated domains of the Theoretical Domains Framework. Design and settingA qualitative study with semi-structured interviews in primary care in Belgium between September 2020 and March 2021. MethodEighteen interviews with long-term hypnotic users were audio recorded, transcribed and thematically analyzed, using the Framework Method. ResultsThe success of discontinuation interventions does not solely rely on patients’ spontaneous sense of striving for improvement. Reinforcement and identity were found to be important domains for motivation. Beliefs about personal capabilities, and about consequences of both BZRA intake and discontinuation, differed between previous and current users. ConclusionMotivation is a multi-layered concept which is not fixed in time. Patient empowerment and goal setting could help long-term BZRA users to lower their intake. As well as public health interventions that might change social attitudes towards the use of hypnotic medication.

Implementing Blended Care to Discontinue Benzodiazepine Receptor Agonist Use for Insomnia: Process Evaluation of a Pragmatic Cluster Randomized Controlled Trial.

Long-term use of benzodiazepine receptor agonists (BZRAs) remains common despite European guidelines advising that these drugs be used in the lowest possible dose and for the shortest possible duration. Half of all BZRAs are prescribed in family practice. This creates a window of opportunity for discontinuation in primary care. Therefore, the effectiveness of blended care for the discontinuation of long-term BZRA use in adult primary care patients with chronic insomnia disorder was tested in a multicenter, pragmatic, and cluster randomized controlled superiority trial in Belgium. In the literature, information on implementing blended care in a primary care setting is scarce. The study aimed to contribute to a framework for the successful implementation of blended care in a primary care setting by increasing our understanding of this complex intervention through an evaluation of e-tool use and views and ideas of participants in a BZRA discontinuation trial. Based on a theoretical framework, this study evaluated the processes of recruitment, delivery, and response using 4 components: a survey on recruitment (n=76), semistructured in-depth interviews with patients (n=18), web-based asynchronous focus groups with general practitioners (GPs; n=19), and usage data of the web-based tool. Quantitative data were analyzed descriptively, and qualitative data were analyzed thematically. For recruitment, the most common barriers were refusal by the patient and the lack of digital literacy, while facilitators were starting the conversation and the curiosity of patients. The delivery of the intervention to the patients was diverse, ranging from GPs who never informed the patient about their access to the e-tool to GPs consulting the e-tool in between consultations to have discussion points when the patient visited. Concerning response, patients' and GPs' narratives also showed much variety. For some GPs, daily practice changed because they received more positive reactions than expected and felt empowered to talk more often about BZRA discontinuation. Conversely, some GPs reported no changes in practice or among patients. In general, patients found follow-up by an expert to be the most important component in blended care, whereas GPs deemed the intrinsic motivation of patients to be the key element of success. An important barrier to implementation by the GP was time. Overall, the participants who had used the e-tool were positive about its structure and content. Nevertheless, many patients desired a more tailored application with feedback from an expert and personal tapering schedules. Strict pragmatic implementation of blended care seems to only reach GPs with an interest in digitalization. Although not superior to usual care, blended care could be a complementary tool that allows tailoring the discontinuation process to the personal style of the GP and the needs of the patient. ClinicalTrials.gov NCT03937180; https://clinicaltrials.gov/ct2/show/NCT03937180.

Attitudes and Difficulties Associated with Benzodiazepine Discontinuation

Long-term use of benzodiazepine receptor agonists (BZDs) may depend on clinicians' BZD discontinuation strategies. We aimed to explore differences in strategies and difficulties with BZD discontinuation between psychiatrists and non-psychiatrists and to identify factors related to difficulties with BZD discontinuation. Japanese physicians affiliated with the Japan Primary Care Association, All Japan Hospital Association, and Japanese Association of Neuro-Psychiatric Clinics were surveyed on the following items: age group, specialty (psychiatric or otherwise), preferred time to start BZD reduction after improvement in symptoms, methods used to discontinue, difficulties regarding BZD discontinuation, and reasons for the difficulties. We obtained 962 responses from physicians (390 from non-psychiatrists and 572 from psychiatrists), of which 94.0% reported difficulty discontinuing BZDs. Non-psychiatrists had more difficulty with BZD discontinuation strategies, while psychiatrists had more difficulty with symptom recurrence/relapse and withdrawal symptoms. Psychiatrists used more candidate strategies in BZD reduction than non-psychiatrists but initiated BZD discontinuation after symptom improvement. Logistic regression analysis showed that psychosocial therapy was associated with less difficulty in BZD discontinuation (odds ratio, 0.438; 95% confidence interval, 0.204-0.942; p = 0.035). Educating physicians about psychosocial therapy may alleviate physicians' difficulty in discontinuing BZDs and reduce long-term BZD prescriptions.

Hazardous use of benzodiazepine receptor agonists in psychiatric clinics in China: electronic prescription database study.

Benzodiazepine receptor agonists (BZRAs) are commonly used clinically and data on their hazardous use from large populations of psychiatric patients is limited. To assess the current status of hazardous BZRA use and related factors in Chinese out-patient psychiatric settings. The study included out-patients with at least one BZRA prescription from five psychiatric settings in east, central and west China in 2018. Demographic and prescription information were extracted from the electronic prescription database. We defined the co-occurrence of overdose and long-term use as hazardous use, and patients whose recorded diagnoses did not meet any indications approved by the Chinese Food and Drug Administration as over-indication users. Additionally, 200 hazardous users were randomly selected for follow-up interview to confirm the actual situation. Among 720 054 out-patients, 164 450 (22.8%) had at least one BZRA prescription; 55.9% of patients were prescribed over-indication and 3% were defined as hazardous users. Multilevel multivariate regression analysis with hospital as a random effect showed that factors associated with hazardous use were older age (18-64 years: β = 0.018; 95% CI 0.013-0.023; >65 years: β = 0.015; 95% CI 0.010-0.021), male (β = 0.005, 95% CI 0.003-0.007), over-indication (β = 0.013, 95% CI 0.012-0.015), more out-patient visits (β = 0.006, 95% CI 0.006-0.006) and more visits to different doctors (β = 0.007, 95% CI 0.007-0.008); 98.5% of hazardous users (197/200) could not be contacted. BZRAs are commonly used and there is a relatively large proportion of over-indication users among Chinese psychiatric out-patients. However, only a small proportion of hazardous users were detected. The study highlights how to use prescription data to support improvements in clinical practice.

Applying the intervention Complexity Assessment Tool to brief interventions targeting long-term benzodiazepine receptor agonist use in primary care: Lessons learned

BackgroundBenzodiazepine receptor agonists (BZRAs) are often prescribed for long-term use. However, guidelines recommend limiting prescriptions to short-term use (< 4 weeks) to reduce the risk of adverse effects and dependence. A recent systematic review reported that brief interventions targeting long-term BZRA use in primary care (e.g., short consultations, written letters to patients) were effective in helping patients to discontinue BZRA medication. However, the complexity of these interventions has not been examined in detail. This study aimed to apply the intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR) to brief interventions targeting long-term BZRA use. MethodsTwo reviewers independently assessed the interventions using the six core iCAT_SR dimensions: organisational level/ category targeted, behaviour targeted, number of intervention components, degree of tailoring, skill level required by those delivering and receiving the intervention. The four optional iCAT_SR dimensions were applied where possible. A scoring system was using to calculate a complexity score for each intervention. Pearson’s correlations were used to assess the relationship between intervention complexity and effect size, as well as the relationship between intervention complexity and number of component behaviour change techniques (BCTs). Inter-rater reliability was calculated using Cohen’s Kappa coefficient.ResultsFour of the six core iCAT_SR dimensions were applied to the interventions with high inter-rater reliability (Cohen’s Kappa = 0.916). Application of the four optional dimensions was prevented by a lack of detail in study reports. Intervention complexity scores ranged from 8 to 11 (median: 11). There was no relationship detected between intervention complexity and either intervention effect size or number of component BCTs.ConclusionsThis study adds to the literature on worked examples of the practical application of the iCAT_SR. The findings highlight how more detailed reporting of interventions is needed in order to optimise the application of iCAT_SR and its potential to differentiate between interventions across the full range of complexity dimensions. Further work is needed to establish the validity of applying a scoring system to iCAT_SR assessments.

Supporting safe and gradual reduction of long-term benzodiazepine receptor agonist use: Development of the SAFEGUARDING-BZRAs toolkit using a codesign approach.

IntroductionLong‐term benzodiazepine receptor agonist (BZRA) use persists in healthcare settings worldwide and poses risks of patient harm.ObjectiveThis study aimed to develop an intervention to support discontinuation of long‐term BZRA use among willing individuals.MethodsThe intervention development process aligned with the UK Medical Research Council's complex intervention framework. This involved a previous systematic review of brief interventions targeting long‐term BZRA use in primary care and qualitative interviews based on the Theoretical Domains Framework that explored barriers and facilitators to discontinuing long‐term BZRA use. A codesign approach was used involving an active partnership between experts by experience, researchers and clinicians. Intervention content was specified in terms of behaviour change techniques (BCTs).ResultsThe SAFEGUARDING‐BZRAs (Supporting sAFE and GradUAl ReDuctIon of loNG‐term BenZodiazepine Receptor Agonist uSe) toolkit comprises 24 BCTs and includes recommendations targeted at primary care‐based clinicians for operationalizing each BCT to support individuals with BZRA discontinuation.ConclusionThe SAFEGUARDING‐BZRAs toolkit has been developed using a systematic and theory‐based approach that addresses identified limitations of previous research. Further research is needed to assess its usability and acceptability by service users and clinicians, as well as its potential to effectively support safe and gradual reduction of long‐term BZRA use.Patient or Public ContributionThe qualitative interview phase included patients as participants. The codesign process included ‘experts by experience’ with either current or previous experience of long‐term BZRA use as collaborators.

Supporting sAFE and GradUAl ReDuctIon of loNG-term BenzodiaZepine Receptor Agonist uSe: development of the SAFEGUARDING-BZRAs toolkit using a co-design approach

Abstract Introduction Long-term benzodiazepine receptor agonist (BZRA) use (&amp;gt;3 months) persists worldwide and poses risks of harm. Effective interventions are needed to address this issue. Aim To develop an intervention to support discontinuation of long-term benzodiazepine receptor agonist (BZRA) use. Methods The intervention development process built on previous qualitative work that used the Theoretical Domains Framework (TDF) to explore perceived barriers and facilitators to discontinuing long-term BZRA use (1). A co-design approach was used whereby lay individuals and professionals worked as equals during the research process based on principles of authentic participation and collaboration (2). The co-design team included five ‘experts by lived experience’ with experience of long-term BZRA use who previously provided input on other related work as patient and public involvement representatives or responded to an expression of interest call on social media. Two online co-design team meetings were held. During the first meeting, a summary of previous findings was presented together with a long-list of behaviour change techniques (BCTs) generated using established mapping matrices in which BCTs were reliably allocated to the TDF. Each team member independently documented their decision as to whether each BCT should be included in a short-list for potential inclusion in the final intervention using online polling software. The a priori decision rule was that 70% of team members had to agree regarding the inclusion/exclusion of a BCT. All other BCTs were then discussed at a follow-up meeting. A finalised list of BCTs for inclusion in the intervention was agreed at the second meeting using a consensus-based approach involving the same decision rule. Potential ways in which BCTs could be operationalised were then discussed. Results Thirty BCTs were discussed and six BCTs were excluded. For example, team members recommended avoiding ‘Social comparison’ as individual circumstances and experiences of discontinuation and associated withdrawal symptoms are unique and not directly comparable. Given the number of included BCTs, the co-design team recommended presenting them as a toolkit. The SAFEGUARDING-BZRAs (Supporting sAFE and GradUAl ReDuctIon of loNG-term BenzodiaZepine Receptor Agonist uSe) toolkit comprises 24 BCTs: ‘Goal setting (behaviour)’, ‘Review behaviour goal(s)’, ‘Review outcome goal(s)’, ‘Feedback on behaviour’, ‘Self-monitoring of behaviour’, ‘Social support (practical)’, ‘Social support (emotional)’, ‘Information about health consequences’, ‘Monitoring of emotional consequences’, ‘Information about emotional consequences’, ‘Prompts/cues’, ‘Habit reversal’, ‘Graded tasks’, ‘Pros and cons’, ‘Comparative imagining of future outcomes’, ‘Social reward’, ‘Self-reward’, ‘Reduce negative emotions’, ‘Distraction’, ‘Adding objects to the environment’, ‘Body changes’, ‘Verbal persuasion about capability’, ‘Focus on past success’ and ‘Credible source’. The toolkit includes recommendations targeted at primary care-based clinicians for operationalising each BCT to support BZRA discontinuation. Conclusion The SAFEGUARDING-BZRAs toolkit has been developed using a systematic, theory-based approach that addresses identified limitations of previous research (e.g. lack of detailed intervention description). In terms of limitations, it is possible that a different group of individuals may have developed a different type of intervention. To overcome this, a priori decision rules were used for decision making. Further research is needed to assess the toolkit’s usability and acceptability by service users and clinicians. References (1) Lynch et al. Health Expect. [in press] DOI: 10.1111/hex.13392. (2) O’Donnell et al. BMC Health Serv Res. 2019;19(1):797

Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study.

To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74-3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31-1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08-2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment. BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.

Trends in the Prescription of Benzodiazepine Receptor Agonists from 2009 to 2020: A Retrospective Study Using Electronic Healthcare Record Data of a University Hospital in Japan.

In recent years, the prescription trends of benzodiazepine receptor agonists (BZRAs) have not been investigated in Japan despite the publication of guidelines that promote cautious use of BZRAs. The prescription trend of BZRAs was assessed using the electronic healthcare records data of a University Hospital in Japan. The data from April 2009 to March 2021 were used. The following three types of outcomes were set: the proportion of patients who were prescribed with BZRAs within those prescribed hypnotics or anxiolytics; the mean number of the types of prescribed BZRAs, and the mean average daily doses of BZRAs. The same analysis was conducted for benzodiazepines (BZDs) and non-benzodiazepines (Z-drugs). As a result, we found that the proportions of patients prescribed BZRAs within those prescribed hypnotics or anxiolytics began to decrease, particularly from 2015 for patients aged <75 years and those aged ≥75 years. Further, the degree of decrease was larger in patients aged ≥75 years. The proportion for BZDs decreased particularly in the study period, and the proportion for Z-drugs also began to decrease approximately from 2016 in patients aged ≥75 years. The results suggest a possibility that guidelines affected the decreased prescriptions of BZRAs.

'I just thought that it was such an impossible thing': A qualitative study of barriers and facilitators to discontinuing long-term use of benzodiazepine receptor agonists using the Theoretical Domains Framework.

IntroductionExisting interventions to reduce long‐term benzodiazepine receptor agonist (BZRA) use lack theoretical underpinning and detailed descriptions. This creates difficulties in understanding how interventions work and how to replicate them in practice. The Theoretical Domains Framework (TDF) can be used to identify behaviour change determinants to target during intervention development.ObjectiveTo explore barriers and facilitators to discontinuing BZRA use from the perspective of both current and previous long‐term BZRA users.Design/Setting and ParticipantsSemistructured TDF‐based interviews were conducted with community‐based individuals with current or previous experience of long‐term BZRA use. Data were recorded, transcribed and analysed using the framework method.ResultsTwenty‐eight individuals were interviewed. Despite commonalities in perceived barriers/facilitators to discontinuing BZRA use within individual TDF domains, individual participants had different experiences of identified determinants of BZRA discontinuation. For example, both similarities and differences existed within and between each participant group in terms of knowledge of the appropriate duration of BZRA use (‘Knowledge’ domain) and experience of withdrawal symptoms (‘Reinforcement’ domain). Compared to previous users, current users typically anticipated more barriers to discontinuing BZRA use and fewer positive consequences of discontinuation.ConclusionThis study reports on barriers and facilitators to discontinuing BZRA use from the perspectives of current and previous long‐term users. The findings highlight the challenging nature of BZRA discontinuation and a multitude of barriers that impact participants’ behaviour regarding BZRA use. Future work will involve developing a theory‐based intervention to support BZRA discontinuation in primary care.Patient ContributionThe study included patients as participants.

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

ObjectiveTo 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.MethodsThis...

Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy.

The long-term use of benzodiazepine receptor agonists (BZRAs) is associated with multiple side effects, such as increased sedation, hangover or an elevated risk of dependency and abuse. Unfortunately, the long-term use of BZRAs is reaching worrying intake rates, and therefore, the need for action is high. It was demonstrated already that the overall willingness of patients for deprescription increased when a slow dose reduction scheme with the possibility for dose increase, if needed, is employed. The current study aims to develop a flexible dosing platform of zolpidem hemitartrate (ZHT) to facilitate such withdrawal therapy. As this is the first report on the extrusion and 3D printing of ZHT, its thermal behaviour and sensitivity towards photolytic degradation was characterised. It was shown that ZHT possesses multiple polymorphs and was especially prone to oxidative photolysis. Next, a variety of immediate release polymers (Eudragit EPO, Kollidon VA64, Kollidon 12PF and Soluplus) were blended and extruded with Polyox WSR N10 to investigate their feedability and printability by mechanical and rheological analysis. The addition of PEO was shown to enable printing of these brittle pharmaceutical polymers, although the processing temperature was deemed critical to avoid surface defects on the resulting filaments. An EPO(70)PEO(30) system was selected based on its suitable mechanical properties and low hygroscopicity favoring ZHT stability. The matrix was blended with 1% or 10% API. The effect of certain printing parameters (caplet size, nozzle diameter, % overlap) on dissolution behaviour and caplet weight/dimensions/quality was assessed. A flexible dosing platform capable of delivering <1 mg and up to 10 mg of ZHT was created. Either caplet modification (incorporation of channels) or disintegrant addition (Primojel, Explotab, Ac-Di-Sol, Primellose and Polyplasdone-XL) failed to achieve an immediate release profile. This study provides the first report of a 3D-printed flexible dosing platform containing ZHT to aid in withdrawal therapy.

The Association between Use of Benzodiazepine Receptor Agonists and the Risk of Obstructive Sleep Apnea: A Nationwide Population-Based Nested Case-Control Study.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway collapse. Benzodiazepine receptor agonists (BZRAs) are associated with pharyngeal muscle relaxation, increased apnea duration, and hypoxia, which might worsen OSA. This study aimed to examine the association between the use of BZRAs and the risk of OSA. The study was conducted using data from the National Health Insurance Database of Taiwan between 2002 and 2011. We only included new users who were never exposed to any BZRAs and identified 1848 participants with OSA, and 1848 matched controls. A logistic regression model was used to determine the association between the use of BZRAs and the development of OSA. BZRA exposure was divided into usage patterns, dosage, duration, and pharmacokinetic class. We found an increased risk of OSA in current users and recent past users compared with distant past users. Patients with a higher cumulative dose of BZRAs were more likely to develop OSA compared to those with a lower cumulative dose. We found an increased risk of OSA in patients treated with BZRAs, especially for current users and those with higher cumulative doses. A reduced risk of OSA was found in Z-drug users compared with benzodiazepine users.