Benzodiazepine Receptor Agonists Research Articles

The effect of education regarding treatment guidelines for schizophrenia and major depressive disorders on psychiatrists' hypnotic medication prescribing behavior: a multicenter study

BackgroundTo examine whether the "Effectiveness of Guideline for Dissemination and Education in psychiatric treatment (EGIUDE)" project affects the rate of prescriptions of hypnotic medication and the type of hypnotic medications prescribed among psychiatrists, for schizophrenia and major depressive disorder in Japan.MethodsThe EGUIDE project is a nationwide prospective study of evidence-based clinical guidelines for schizophrenia and major depressive disorder in Japan. From 2016 to 2021, clinical and prescribing data from patients discharged from hospitals participating in the EGUIDE project were used to examine hypnotic medication prescriptions The prescribing rate of hypnotics and the prescribing rate of each type of hypnotic (benzodiazepine receptor agonist, nonbenzodiazepine receptor agonist, melatonin receptor agonist, and orexin receptor antagonist) were compared among patients who had been prescribed medication by psychiatrists participating in the EGUIDE project and patients who had been prescribed medication by nonparticipating psychiatrists. Multivariate logistic regression analysis was performed to examine the effect of the EGUIDE project on the prescription of hypnotic medications.ResultsA total of 12,161 patients with schizophrenia and 6,167 patients with major depressive disorder were included. Psychiatrists participating in the EGUIDE project significantly reduced the rate of prescribing hypnotic medication and benzodiazepine receptor agonists for both schizophrenia (P < 0.001) and major depressive disorder (P < 0.001) patients.ConclusionThis is the first study to investigate the educational effects of guidelines for the treatment of psychiatric disorders on psychiatrists in terms of prescribing hypnotic medications to patients. The EGUIDE project may play an important role in reducing hypnotic medication prescription rates, particularly with respect to benzodiazepine receptor agonists. The results suggest that the EGUIDE project may result in improved therapeutic behavior.

Trends in central nervous system-active polypharmacy among people with multiple sclerosis.

People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS. The objective is to measure the prevalence of CNS-active polypharmacy in pwMS. This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants. The number of subjects included at each time point ranged from 23,917 subjects in 2008 to 55,797 subjects in 2021. In 2021, subjects with CNS-active polypharmacy were more likely to be 46-65 years of age and have CNS-related comorbidities compared to those without CNS-active polypharmacy. From 2008 to 2021, the age-adjusted prevalence of CNS-active polypharmacy among female subjects increased from 19.8% (95% confidence interval (CI) = 19.1-20.4) to 26.4% (95% CI = 25.9-26.8) versus 15.9% (95% CI = 14.8-17.0) to 18.6% (95% CI = 17.9-19.2) in male subjects. The prevalence of CNS-active polypharmacy has increased among people with MS with a growing disparity by sex.

“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?

0399 Masked Tapering and Augmented CBTI Improves Benzodiazepine Receptor Agonist Discontinuation in a Randomized Trial

0399 Masked Tapering and Augmented CBTI Improves Benzodiazepine Receptor Agonist Discontinuation in a Randomized Trial

Comparison of patients with benzodiazepine receptor agonist-related psychiatric disorders and over-the-counter drug-related psychiatric disorders before and after the COVID-19 pandemic: Changes in psychosocial characteristics and types of abused drugs.

To investigate changes in the clinical characteristics of patients who abused benzodiazepine receptor agonists (BZRA) or over-the-counter (OTC) drugs before and after COVID-19 based on the 2018 and 2022 data of the "Nationwide Psychiatric Hospital (NPH) Survey on Drug-related Psychiatric Disorders." A total of 446 and 155 cases, and 435 and 273 cases, who mainly abused BZRAs or OTC drugs, respectively, were extracted from the database of the two NPH Surveys. Demographic variables, education, employment, criminal record, drug use during the previous year, psychiatric diagnosis, and types of abused drugs were compared between 2018 and 2022. A comparison of BZRA abusers revealed a decreased number of users during the previous year and an increase in the comorbidity rate of other disorders (F3 and F4 in ICD-10) in 2022. Etizolam, flunitrazepam, triazolam, and zolpidem were used most in both years, with an increase in zolpidem and a decrease in triazolam in 2022. A comparison of OTC drug abusers revealed a higher proportion of women and young patients in 2022. An increase in the comorbidity rate of F3 and F9 and a significant increase in the use of dextromethorphan products were observed in 2022, although codeine products were in the majority in both years. By comparing NPH Surveys before and after the COVID-19 pandemic, both BZRA abusers and OTC drug abusers present complex pathologies, requiring tailor-made treatment. The younger OTC drug abusers were particularly evident among women, and the abuse of dextromethorphan-containing OTC drugs has increased alarmingly.

EXPRESSION OF NEUROFILAMENTS IN THE RETINA IN EXPERIMENTAL DIABETIC RETINOPATHY AND THE INFLUENCE OF THE BENZODIAZEPINE RECEPTOR AGONIST CARBACETAM

Background. One of the typical neurochemical pathogenetic mechanisms causing the dysfunction of retinal neurons in diabetic retinopathy (DR) is a deficiency of GABA-ergic mediation. To some extent, this justifies the prospect of using GABA receptor modulators, including benzodiazepines.&#x0D; Aim: To determine the expression of neurofilaments in the initial stages of the experimental DR development and the influence of the benzodiazepine receptor agonist Carbacetam.&#x0D; Materials and methods. DR was modeled in 35 three-month-old male Wistar rats by a single injection of streptozotocin (50 mg/kg; Sigma-Aldrich, Co, China). The rats were divided into 3 groups: control, with the introduction of Insulin (30 Units; Novo Nordisk A/S, Bagsvaerd, Denmark) and with the introduction of Insulin and Carbacetam (5 mg/kg). NF-H neurofilaments (ThermoFisher Scietific, USA) were detected in the retina by immunohistochemistry.&#x0D; Results. Before DR modeling, NF-H-positive staining was detected in the inner and outer layers of the retina in mainly longitudinal fibers of different lengths, which corresponded to the axons of horizontal and amacrine cells; as well as in fibers and axonal hills of ganglion neurons. In the dynamics of the DR development in the plexiform layers of the retina, a progressive decrease in the intensity of staining was observed. In the optic fiber layer, staining was concentrated around dilated microvessels that tended to form microaneurysms. On the 28th day, NF-H-positive staining disappeared in the inner plexiform layer. Administration of Insulin with Carbacetam prevented the loss of NF-H-positive staining in the layers of the retina.&#x0D; Conclusion. The use of the benzodiazepine receptor agonist Carbacetam may be a promising direction for the correction of retinal neurodegeneration in DR.

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.

Prescriber Acceptability of a Direct-to-Patient Intervention for Benzodiazepine Receptor Agonist Deprescribing and Behavioural Management of Insomnia in Older Adults.

Behavioural treatments are recommended first-line for insomnia, but long-term benzodiazepine receptor agonist (BZRA) use remains common and engaging patients in a deprescribing consultation is challenging. Few deprescribing interventions directly target patients. Prescribers' support of patient-targeted interventions may facilitate their uptake. Recently assessed in the Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study, Sleepwell (mysleepwell.ca) was developed as a direct-to-patient behaviour change intervention promoting BZRA deprescribing and non-pharmacological insomnia management. BZRA prescribers of YAWNS NB participants were invited to complete an online survey assessing the acceptability of Sleepwell as a direct-to-patient intervention. The survey was developed using the seven construct components of the theoretical framework of acceptability (TFA) framework. Respondents (40/250, 17.2%) indicated high acceptability, with positive responses per TFA construct averaging 32.3/40 (80.7%). Perceived as an ethical, credible, and useful tool, Sleepwell also promoted prescriber-patient BZRA deprescribing engagements (11/19, 58%). Prescribers were accepting of Sleepwell and supported its application as a direct-to-patient intervention.

Is there a better way to wean chronic benzodiazepine receptor agonists use by substituting a DORA (and starting CBT-I)?

Is there a better way to wean chronic benzodiazepine receptor agonists use by substituting a DORA (and starting CBT-I)?

Insomnia Guidelines—The European Update 2023

The last ten years have seen the development and publication of numerous national and international guidelines devoted to the diagnosis and treatment of insomnia. These include guidelines by the American College of Physicians (ACP), the American Academy of Sleep Medicine (AASM), the British Sleep Society (BSS), the German Sleep Society (GSS), and the European Sleep Research Society (ESRS). Though coming from very diverse authors and backgrounds, these guidelines by and large agree concerning the therapeutic recommendations: cognitive behavioral treatment of insomnia (CBT-I), a multicomponent psychotherapeutic intervention, is unequivocally recommended as a first-line treatment. In this report, we will focus on the most recent guideline update from the ESRS, which was published in November 2023. After suggesting a careful diagnostic procedure, CBT-I, both applied face to face (F2F) or digitally (dCBT-I), is again recommended as a first-line treatment based on the available evidence. Hypnotic medications like benzodiazepines (BZ), benzodiazepine receptor agonists (BZRA), sedating antidepressants, and others are approved for short-term-treatment of up to four weeks. Orexin receptor antagonists (i.e., daridorexant) and prolonged release melatonin are considered as options for longer-term treatment when carefully considering the advantages and disadvantages. Both light therapy and exercise regimens were viewed as promising; however, they still lack convincing evidence for the time being. Given the fact that not every patient responds satisfactorily or even remits following CBT-I or other treatment options, the research agenda calls for the development and evaluation of new therapeutic avenues and combination therapies.

‘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.

Benzodiazepine receptor agonist carbacetam modulates the level of vascular endothelial growth factor in the retina of rats with streptozotocin-induced diabetes

One of the primary mechanisms of retinal neurodegeneration in diabetes mellitus is gamma-aminobutyric acid (GABA) deficiency that makes the use of GABA-benzodiazepine receptor modulators a promising option for the correction of this diabetic complication. The aim of this study was to determine the effect of the benzodiazepine receptor agonist carbacetam on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in retina of rats with hyperglycemia. Experimental diabetes was modeled by a single administration of streptozotocin (50 mg/kg) to three-month-old male Wistar rats. Immunoblotting and immunohistochemical studies were performed using monoclonal antibodies against VEGF and HIF-1α. It was shown that the development of diabetic retinopathy (DR) at the early stages was accompanied by a progressive multifold increase in the retina content of VEGF on 7-28 days and HIF-1α on 28th day. Insulin and insulin+carbacetam treatment significantly alleviated diabetes-induced overexpression of both HIF-1α and VEGF. Carbacetam was shown to block the diabetogenic increase in VEGF content in retina. The introduction of insulin with carbacetam significantly reduced the expression of VEGF and the development of specific morphological manifestations of DR. Thus, restoration of GABA-ergic signaling can be used as a promising therapeutic option for the correction of DR disorders. Keywords: carbacetam, GABA-benzodia­zepine receptors, HIF-1α hyperglycemia, retinopathy, streptozotocin-induced diabetes, VEGF

A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists.

Although novel hypnotics have recently emerged, there are currently no data comparing the clinical potency of benzodiazepine receptor agonists (BZRAs) and novel hypnotics, or the effectiveness of different methods of switching between them. This study examined how novel hypnotics might help reduce BZRA use in real-world practice. 289 patients with psychiatric disorders who took BZRAs for over 1 year before switching to either of 2 dual-orexin receptor antagonists (DORAs; suvorexant [SUV] or lemborexant [LEM]) or a melatonin receptor agonist (ramelteon [RMT]) were enrolled. We collected data on BZRAs at baseline and 3 months after commencement of SUV/LEM/RMT. Significant reductions in BZRAs were observed for all 3 agents: -4.10, -2.80, and -1.65 mg in diazepam-equivalent doses in the SUV, LEM, and RMT groups, respectively. Dose reduction was significantly greater in the DORA than the RMT group (F = 15.053, P < .001). Within the DORA group, dose reduction was significantly greater in patients taking SUV than those taking LEM (F = 4.337, P = .043). The switching success rate did not differ among the switching methods for any of the hypnotics. The reduction rate of BZRAs achieved by the switch fell into their equivalent-potency range estimated from clinical trials. The results suggest that DORAs can replace approximately 1 tablet of a BZRA. The difference in dose reduction between DORAs and RMT reflected the greater sleeping potency of the DORAs, whereas that between SUV and LEM might have reflected patient backgrounds: patients taking LEM may have been more strongly dependent on BZRAs. Tachibana M, Kanahara N, Oda Y, Hasegawa T, Kimura A, Iyo M. A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists. J Clin Sleep Med. 2024;20(4):603-613.

Is it possible to deprescribe benzodiazepine receptor agonists in older adults?

Aim: to analyze the viability and related factors for deprescribing benzodiazepine receptor agonists (BZRA).Methods: this is a longitudinal, prospective, interventional study performed with older adults assisted at a geriatric psychiatry outpatient clinic; these were divided into two groups: BZRA users and non-users. The instruments used in this study were a general questionnaire, the Geriatric Depression Scale (short form), the Geriatric Anxiety Inventory, and the Pittsburgh Sleep Quality Index.Results: we evaluated 74 patients, 40 (54.1%) of which were BZRA users and 34 (45.9%) were non-users, with an average age of 71.3 ± 7.5 years. Patients who used BZRA had a higher dropout rate of the deprescription process 26 (65%). Seven patients completely stopped using BZRAs (17.5%) and five reduced their use (12.5%). The mean scores for depression and anxiety symptoms were lower at the final assessment. As to sleep quality, BZRA users presented higher baseline values and both groups presented reductions in scores at the end of the treatment.Conclusion: deprescribing is viable and safe. However, there is resistance by both the patient and prescribers. The levels of anxiety, depression, and sleep quality improved after discontinuing BZRA.

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Comparative short-term safety and efficacy of hypnotics: A quantitative risk-benefit analysis.

Several professional societies have provided recommendations for prescribing medications for insomnia. None has provided an integrative analysis that concurrently quantifies safety and efficacy (e.g., risk-benefit ratios). This represents an important gap for informing clinician decision-making. Accordingly, the aim of the present review is to provide such an analysis for five classes of sleep-promoting medications. Adverse event data values were extracted from the most recent FDA-approved package inserts and converted to an integer before being placebo-adjusted and standardized as a rate per 1000 (AEr). Efficacy data, pre-to-post self-reported data for active and placebo conditions were acquired from pivotal trials identified in "white papers" and systematic reviews/meta-analyses. Weighted effect sizes were calculated for subjective sleep latency, wake time after sleep onset and total sleep time, and then were averaged by medication class for each sleep continuity variable. Overall efficacy was represented by a single variable, SWT (sleep latency + wake time after sleep onset + total sleep time). Risk-benefit was represented using a simple ratio value. For safety, it was found that melatonin receptor agonists had the lowest adverse event rate (AEr = 43.1), and non-benzodiazepine benzodiazepine receptor agonists had the highest rate (AEr = 255.0). For efficacy, it was found that the pre-to-post placebo adjusted effect sizes were largest for benzodiazepines (effect size = 1.94) and smallest for melatonin receptor agonists (effect size = 0.109). For risk-benefit, histamine antagonist had the most favourable profile (risk-benefit = 69.5), while melatonin receptor agonist had the least favourable profile (risk-benefit = 395.7). Overall, the combined metric for risk-benefit suggests that treatment with a histamine antagonist is optimal and potentially represents the best first-line therapy for the medical management of insomnia.

From prescribing dilemma to knowledge in practice: The ontological politics of benzodiazepines and Z-drugs

The discrepancy between official guidelines and clinical practice is hardly more pronounced than in the case of benzodiazepines and Z-drugs, also known as benzodiazepine receptor agonists (BZRA). Using social-constructionist positioning theory, we unravel how health care professionals deal with the dilemma of prescribing this medication. Our results reveal a prescribing spectrum that is discursively organised around four different storylines used by professionals. The storylines are organised along three axes that are related to a) prescribers' opinions on prescribing and the negotiation of the related risks, b) the power dynamics between provider and patient in the prescribing process and c) the rhetorical use of arguments. The discerned storylines allow us to explore the emotional and moral side of prescribing and demarcate clinical mindlines -internalised tacit guidelines-that professionals adhere to when they prescribe. By relying on Annemarie Mol's conceptualisation of ontological politics, we explain how these storylines enact multiple versions of this class of medication and justify seemingly contradictory prescribing practices.

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.