Use Of Benzodiazepines Research Articles

Protein phosphatase 2A inhibitors: a possible pharmacotherapy for benzodiazepine dependence.

Benzodiazepines (BZDs) activate the γ-aminobutyric acid (GABA) subtype A (GABAA) receptors, and thus are widely used medicines for the treatment of anxiety and insomnia. For chronic use, tolerance to BZDs is a major problem. Patients with chronic insomnia that develop tolerance to BZDs lose therapeutic effects but also potentially suffer from BZD dependence resulting in BZD withdrawal. The development of such treatments is important for the appropriate use of BZDs. Research articles regarding investigation of BZD dependencewere searched on PubMed, Embase, and Scopus databases using keywords "benzodiazepine", "dependence", "treatment". When BZDs are taken chronically, continuous GABAA binding results in up-regulation of α-amino-3-hydroxy-5-methyl-4-lisoxazolepropionic acid (AMPA) glutamate receptor function and release of brain-derived neurotrophic factor (BDNF). Released BDNF binds to its specific receptor tropomyosin-related kinase receptor B (TrkB). Enhanced BDNF-TrkB signaling activates protein phosphatase 2A (PP2A). Activated PP2A dephosphorylates GABAA receptors, resulting in the downregulation of the GABAA receptor function. Reduced GABAA receptor function augments long-term potentiation (LTP), AMPA-mediated glutamatergic neuroplasticity, by reducing LTP inhibition by GABAA receptor function. Augmented LTP enhances extreme anxiety, which leads to BZD dependence. Therefore, iInhibiting dephosphorylation of the GABAA receptor by PP2A, PP2A inhibitors could reduce LTP and anxiety, restoring BZD effectiveness and resulting in possible therapeutic effects for BZD dependence.

Abstract 4140180: The Effect of Benzodiazepine Use in Patients with Atrial Fibrillation and Obstructive Sleep Apnea

Introduction: Sleep apnea is a common sleep disorder that can worsen atrial fibrillation(AF) prognosis. Benzodiazepines(BZD) are commonly prescribed for insomnia, which often accompanies sleep apnea. However, BZDs have been associated with worsening of sleep apnea due to respiratory depression, pharyngeal muscle relaxation, and increase of arousal threshold, which all may lead to prolonged hypoxia. There is little research on the effect of BZD use in AF patients with sleep apnea. Therefore, the objective of this study is to investigate the effects of BZD usage on outcomes in the AF population with sleep apnea. Methods: Data from patients with AF and sleep apnea seen at Tulane Medical Center between 2010 and 2019 was obtained from Research Action for Health Network(REACHnet), a Clinical Research Network in PCORnet®. Patients with AF and sleep apnea were divided between those with a prescription of BZD and those without BZD. These two groups were compared using the Kaplan-Meier method for time-to outcome for all-cause mortality, ischemic stroke, myocardial infarction(MI), and hospitalizations in the five years following their AF diagnosis. Cox regression analysis was used to investigate proportional hazards and control for demographics, comorbidities, and medication use. Results: There were 524 total patients included with AF and sleep apnea. Of these, 413(78.8%) were not prescribed BZDs, while 111(21.1%) were taking BZDs. Use of BZDs was associated with worse outcomes. In the no BZD and the BZD group over the 5 years following AF diagnosis, the rate of mortality was 6.1% and 12.6%(p<.001), the rate of ischemic stroke was 16% and 23.4%(p=.008), the rate of MI was 11.9% and 22.5%(p<.001), and the rate of hospitalization was 51.8% and 59.5%(p<.001), respectively. In multivariate Cox regression, use of BZD was associated with higher mortality(HR: 2.65; CI: 2.26-3.05; p=.013) and hospitalization(HR: 2.15; CI: 1.99-2.31;p<.001). Conclusion: BZD use was associated with an over 2-fold increase in all-cause mortality and hospitalizations in patients with AF and sleep apnea. This suggests that BZDs should be used with caution in this patient population, and other treatment modalities for insomnia should be considered.

Experiences of treating problematic over the counter and prescription only medication use in substance misuse services

Abstract Introduction There are growing concerns about the misuse of over the counter (OTC) and prescription only medication (POM), due to the associated negative socioeconomic and health implications1. To improve care delivery, stigma needs to be addressed and more needs to be known about the perspectives of staff who are working in substance misuse services (SMS)2. Aims To use confidential semi-structured interviews, to explore the experiences of community English SMS staff who have supported adults that have misused OTC/POM. Methods This research was conducted across five community adult English SMS operated by a national treatment provider. Individuals were eligible for participating in semi-structured interviews if they had current experience of working in a community SMS role which involved supporting adults who had misused OTC/POM, were at least 18 years of age and provided informed consent. Potential participants self-identified as being eligible and interested in being included, after receiving the participant information sheet. The interviews explored their experience of working in SMS and supporting people who have misused OTC/POM, and potential changes to current SMS provision. Thematic analysis of the audio-recording transcripts was undertaken using NVivo®. This research was funded by a Research Award from Pharmacy Research UK and the College of Mental Health Pharmacy [PRUK_CMHP-2019-2-RG]. This research was approved by Humankind/EDP and Aston University’s Life and Health Sciences Ethics Committees (ID#1655). Results Organising interviews was challenging due to pandemic-related work pressures, between October 2020 and January 2021. Thematic analyses of twenty SMS staff transcripts was undertaken and data saturation was thought to have been achieved. Three overarching themes were identified: characteristics of OTC/POM misuse; different groups of people; and negative experiences (with six sub-themes: lack of awareness of risk of harm; unmanaged health conditions; withdrawal symptoms; side-effects; problematic behaviours; and treatment pathways). Oral dependent use of opioids (especially codeine products), benzodiazepines and gabapentinoids predominated. Polypharmacy and the use of other substances sometimes occurred. OTC/POM misuse was associated with a wide range of adverse socioeconomic, physical, and psychological effects. Unmanaged withdrawal symptoms caused concern, contributed to perpetuating misuse, and sudden cessation in supplies created risks. Discussion and Conclusion This study had a unique focus on the experiences of third sector English SMS staff. OTC/POM misuse (and withdrawal symptoms) should be routinely enquired about during healthcare reviews, and tailored harm reduction, pharmacological and psychosocial interventions offered. Increased awareness, vigilance for associated safeguarding issues, and more training is required. SMS should sensitively consider how to incorporate the views of staff with lived experience to further optimise service delivery co-production. As staff were all employed by the same SMS provider, future research, conducted in SMS operated by other providers, and covering a wider geography, may enable more information to be shared, more participants to be recruited, and the results more generalisable. Repeat interviews and member-checking may improve assurance in the findings. The possible need for different SMS for those who only misuse OTC/POM without exacerbating stigma requires further exploration. Future research should identify if demographic characteristics and treatment needs differ by OTC/POM type.

Letter to the Editor Regarding 'Excessive Use of Benzodiazepines Is a Risk Factor for Endotracheal Intubation in Children Who Present to Emergency With Prehospital Status Epilepticus'.

Letter to the Editor Regarding 'Excessive Use of Benzodiazepines Is a Risk Factor for Endotracheal Intubation in Children Who Present to Emergency With Prehospital Status Epilepticus'.

Enlarged choroid plexus related to atrophy of hippocampal subfield volumes and glymphatic dysfunction in benzodiazepine use disorder.

The aim of this study was to explore the relationship of choroid plexus (CP) volume with hippocampal subregion volume and glymphatic system in patients with benzodiazepine use disorders (BUD). Eighty-four participants were recruited including 23 patients with BUD, 29 patients with chronic insomnia (CI) and 32 healthy controls (HC). The morphological alterations in CP, hippocampal subfield volumes and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index were compared between the three groups and the relationships between CP volume and hippocampal subfield volumes and the glymphatic system were further investigated. Compared with the HC individuals, the CP volumes augmented and hippocampal subfield volumes reduced in patients with BUD (P < .05) but not in patients with CI (P > .05). In patients with BUD, there were extensive relationships between augmented CP volume and decreased hippocampal subfield volumes (P < .05, r = -0.421--0.513). CP volume was negatively related with the DTI-ALPS index (r = -0.582, P = .004) within the BUD group. In patients with BUD, the volume of bilateral cornu ammonis (CA)1 body, molecular layer (ML) body, hippocampal tail, left CA1 head volumes, right dentate gyrus body volumes, and right CA4 body volumes were positively related with the Montreal Cognitive Assessment scores (P < .05, r = 0.422-0.683). Right CA1 and ML body volumes positively related with the Mini-Mental State Examination scores (P < .05, r = 0.503-0.575). The enlarged CP related to atrophy of hippocampal subfield volumes and the glymphatic system dysfunction were shown in BUD patients.

Catatonia in anti-NMDA receptor encephalitis: a case series and approach to improve outcomes with electroconvulsive therapy

BackgroundAnti-N-methyl-D-aspartate (NMDA) receptor encephalitis has been recognised to present with the syndrome of catatonia. In severe cases dysautonomia is representative of malignant catatonia. The treatment with benzodiazepines (BZDs) and electroconvulsive therapy (ECT) may decrease morbidity and mortality in patients presenting with anti-NMDA receptor encephalitis and catatonia.MethodsThis is a retrospective case series of eight patients with anti-NMDA receptor encephalitis treated with ECT. We use clinical prediction scores (Clinical Assessment Scale for Autoimmune Encephalitis [CASE] and anti-NMDAR Encephalitis One-Year Functional Status scores) to compare expected outcomes and observed outcomes.ResultsCASE scores in our group ranged between 5 and 19, with a mean score of 13.8 (median 15.5). NEOS scores ranged from 2 to 4, with a mean and median of 3. Of the eight patients, six had a favourable modified Rankin Score (0–2) at a follow-up of 8 to 12 months. Patients received an average of 29.9 ECT treatments in total.ConclusionsBased on clinical prediction scores, this cohort had better than expected functional outcomes. We discuss the use of BZDs and ECT in these cases and propose a treatment algorithm for patients who present with catatonic syndrome in anti-NMDA receptor encephalitis.

Anesthésie locale comparée à l'anesthésie locorégionale dans les procédures TAVI par voie transfémorale

IntroductionTranscatheter aortic valve implantation (TAVI) has become the treatment of choice for the most fragile patients with severe aortic stenosis. The transfemoral route is preferred as the simplest and safest. The aim of our study was to compare the efficacy, tolerance and safety of local vs. locoregional anesthesia in trans-femoral TAVI procedures. Material and methodThis was a single-center retrospective study. Patients treated with femoral TAVI between February 25 and November 15, 2022 at the University Hospital of Reims were included, and two groups (local and locoregional anesthesia) were compared. ResultsTAVI success rate (92.9%), death rate (3.0%) and procedure duration (90.5 ± 13.5 minutes) did not differ between groups (p = 0.18, 0.15 and 0.55 respectively). For intra- and post-procedural treatments, the use of sedation, analgesics and benzodiazepines did not differ between groups. The cumulative dose of Remifentanil used per-procedure was lower in the local anesthesia group than in the locoregional anesthesia group (148.6 ± 71.9 mcg vs. 208.9 ± 110.0 mcg; p = 0.025). ConclusionsIn this non-randomized retrospective study, local and locoregional anesthesia had comparable safety and efficacy in transfemoral TAVI procedures. In a constrained context and with a view to simplification, these results encourage transfemoral TAVIs to be performed under local anaesthesia, and to consider a “PCI-like” approach, without the presence of an anaesthetist, for selected patients without respiratory, musculoskeletal or agitation disorders, or vascular approach difficulties.

Does concomitant diazepam and ethanol use modulate age-related cognitive decline in mice?

BackgroundConcomitant use of alcohol and benzodiazepines are described among elderly, raising concerns about their combined impact on memory. We aimed to evaluate the long-term impact of chronic diazepam use associated with ethanol intoxication on memory in aging mice. MethodsTwelve-month-old male C57BL6 mice were assigned into 4 groups: ethanol (OH), diazepam (DIA), diazepam + ethanol (DOH) and control (CTL). For 16 weeks, ethanol was available ad libitum and diazepam was mixed with food. Behavioral testing, performed during and after treatment cessation included working memory and visual recognition memory assessment. The second session was implemented with spatial reference learning and memory assessment in the Barnes maze test. In vivo magnetic resonance spectroscopy (MRS) acquisitions were performed to quantify hippocampal metabolites during and after cessation treatment. ResultsDuring treatment, visual recognition memory was significantly different between groups with the DIA group exhibiting the worst performance. MRS acquisition highlighted higher glutamate and choline levels in OH and DOH groups in comparison to CTL and DIA groups. After treatment wash-out, there was no difference between in the different memories evaluated. Only the learning phase of the spatial reference memory test differed significantly with worst performance in OH groups. Three months after treatment cessation, there was no remanent effect of diazepam + ethanol on hippocampal metabolites changes. ConclusionsWe did not evidence additive effect of ethanol and diazepam on memory and hippocampal metabolite levels. The disturbances observed during treatment were no remanent, highlighting the benefits of discontinuing these substances.

Strategies to Limit Benzodiazepine Use in Anesthesia for Older Adults

Despite guidelines recommending avoidance of benzodiazepine administration to older patients, many of them now receive benzodiazepines as a part of anesthesia care. The effectiveness of clinician- and patient-facing interventions to discourage such use remains insufficiently characterized. To evaluate the effect of clinician peer comparison, patient informational mail, or a combination of these interventions compared with usual care on the rate of perioperative benzodiazepine administration to older patients. This 2 × 2 factorial, stepped-wedge, cluster randomized clinical trial of a corporate quality improvement initiative was conducted between August 8, 2022, and May 28, 2023, across 415 hospitals, surgery centers, and physician offices in 8 US states served by anesthesia clinicians from a national anesthesia practice. Participants were adults aged 65 years or older who underwent an elective surgical or endoscopic procedure with general anesthesia. Data analyses followed the intention-to-treat principle. Patients were randomly assigned to 1 of 4 groups-clinician peer comparison (wherein clinicians received feedback regarding their performance compared with other clinicians in the practice), patient informational mail (wherein patients received an informational letter encouraging them to have a discussion regarding medication selection with their clinician on the day of surgery), both interventions, or usual care (no intervention). Rate of benzodiazepine administration during anesthesia care and patient satisfaction with anesthesia care (measured by the Anesthesia Patient Satisfaction Questionnaire, version 2). Among the 509 269 enrolled participants (255 871 females [50.2%]; mean [SD] age, 74 [7] years), 81 363 (16.0%) were assigned to clinician peer comparison, 98 520 (19.3%) to patient informational mail, 169 712 (33.3%) to both interventions, and 159 674 (31.4%) to usual care. Among patients who received benzodiazepine during anesthesia care, 24.5% were in the usual care group compared with 19.7% in the clinician peer comparison group, 20.0% in the patient informational mail group, and 19.7% in the combination group. After adjustment for time, none of the study interventions were associated with lower odds of benzodiazepine administration compared with usual care (odds ratio [OR], 1.02 [95% CI, 0.98-1.07]; P = .35 for clinician peer comparison; OR, 1.01 [95% CI, 0.96-1.05]; P = .81 for patient informational mail; and OR, 1.11 [95% CI, 1.05-1.16]; P < .001 for combined interventions). Satisfaction scores were high in all groups and did not vary by treatment assignment. This randomized clinical trial found that clinician peer comparison, patient informational mail, or a combination of both interventions did not reduce benzodiazepine administration to older patients compared with usual care; patient satisfaction remained high throughout the study. Overall, the findings suggest a need to explore other patient-targeted interventions to improve anesthesia care. Clinicaltrials.gov Identifier: NCT05436392.

Association of Benzodiazepine Prescription With Short-Term Prognosis in Elderly Patients Attended in Emergency Department: Results From the EDEN PROJECT.

Benzodiazepine prescription is a growing phenomenon among the elderly population. However, information related to the frequency of these drugs among the elderly population attending in emergency departments (ED) and its impact over prognosis is scarce. The aim of this study is to assess the prevalence of benzodiazepine prescription and to analyze its association with short-term prognosis in elderly patients attended in ED. A retrospective analysis of the EDEN (Emergency Department Elderly in Need) cohort was conducted. This registry included all elderly patients attending in 52 Spanish EDs for any condition, between April 1st and 7th in 2019. Socio-demographic data, comorbidities, and medication were recorded by consulting the patient's electronic health records. The assessed outcomes consisted on new ED visit, hospitalization, and mortality at 30 days after the first ED visit, associated with the use of benzodiazepines at baseline in comparison with no prescription of benzodiazepines. Crude and adjusted logistic regression analyses including patient's comorbidities were performed. Two sensitivity analyses were performed considering concomitant prescription of other central nervous system depressants as well as direct discharge from the ED. 25 557 patients were evaluated (mean age 78 [IQR: 71-84]). 7865 (30.8%) patients were taken benzodiazepines at admission. After adjustment for comorbidities and other central nervous system drugs, benzodiazepine prescription was associated with ED revisit [OR: 1.10 (95%CI: 1.03-1.18)]. Similar results were found in the sensitivity analysis, eliminating patients with central nervous depressors [OR: 1.11 (1.03-1.25)] and patients discharged to home [OR: 1.13 (1.04-1.23)]. No association was found between the use of these drugs and new hospitalizations [OR: 0.90 (0.77-1.05)] or mortality 30 days after discharge [OR: 1.01 (0.88-1.18)]. The results held for all three outcomes in the sensitivity analyses. The use of benzodiazepines is a frequent phenomenon among the elderly population attended in the ED, being associated with an increased risk of new visits to the emergency room, but not with an increased risk of 30-day hospitalization or mortality.

Perspectives on oral benzodiazepine use for anxiety in Mohs micrographic surgery: A response to the Australian survey.

This letter responds to the recent Australian survey by Harris and Lee (Australas J Dermatol, 2024, doi: 10.1111/ajd.14361) on the use of oral benzodiazepines for anxiety management in Mohs micrographic surgery (MMS). While commending the authors' efforts, we provide additional perspectives on current practices, recent evidence and safety considerations. We highlight the alignment with U.S. practices, discuss a recent randomized controlled trial supporting diazepam's efficacy and emphasize the importance of non-pharmacological interventions. The letter also addresses the need for flumazenil availability and calls for standardized guidelines and further research to optimize patient care in MMS.

Hypnotic use and the risk of cardiovascular diseases in insomnia patients

Abstract Background Insomnia, commonly treated with hypnotic agents, is an independent risk factor of cardiovascular diseases. Previous research demonstrated the detrimental effect of hypnotics on the prognosis of cardiovascular patients. Purpose We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia. Methods In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting and competing risk models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of hypnotics-related genes and cardiovascular disease association. The genome-wide association data of CHD, HF, and stroke were there large-scale genome-wide association analyses. Tissue-specified expression quantitative trait loci (eQTL) data was derived from BrainSeq phase II. Results During a median follow-up of 14.3 years, the matched cohort documented a total of 1,019 CHD cases, 406 HF cases, 285 stroke cases, and 197 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality (Figure 1). The inverse probability of treatment weighting and competing risk models didn’t alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. However, GABRG1—a drug target for benzodiazepines—was associated with heightened risks for heart failure, and ischemic stroke (Figure 2). Conclusions Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Z-meds are safe regarding the risk of cardiovascular outcomes in the UKB population with insomnia.Figure 1Figure 2

Post-injury use of opioid analgesics in patients with traumatic injury: A registry-based study.

Opioid analgesics are commonly used to treat acute and chronic pain following traumatic injury. Psychiatric comorbidity has been reported to be associated with increased pain and persistent opioid use. Our aims were to determine the extent of post-injury opioid use and assess whether pre-injury antidepressant, benzodiazepine, and z-hypnotic drug use is associated with increased post-injury opioid use. Data on trauma patients aged 15 years and older included in the Oslo University Hospital Trauma Registry between 2005 and 2014 was linked to data from the Norwegian Prescription Database. We identified opioid dispensing within the first 90 and 365 days following trauma and determined subsequent persistent use. Multivariable logistic regression was applied to examine associations between pre- and post-injury drug use. 3912 of 11,057 patients (35.4%) had opioids dispensed within 90 days after trauma, and 4644 (42.0%) within 365 days. Among 9800 previously opioid-naïve, the proportions were 33.0% and 39.0%, respectively. One year after the first post-injury opioid dispensing, 9.6% of all opioid users and 4.5% of new users were defined as persistent users. Pre-injury benzodiazepine use and z-hypnotic use was associated with new persistent opioid use (adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 1.47-3.45, and aOR 2.04; 95% CI 1.33-3.13, respectively), whereas pre-injury antidepressant use was not (aOR 1.49; 95% CI 0.97-2.30). Opioid use after trauma is widespread. Development of persistent use is limited, particularly in previously opioid-naïve patients. Pre-injury benzodiazepine or z-hypnotic use seem to increase odds of new persistent use. This large registry-based study adds to the body of knowledge on opioid use beyond in-hospital care in patients having sustained traumatic injury, a field which is scarcely investigated and not yet fully understood. It suggests that both previous drug therapy and the nature of opioid treatment initiation may affect outcome. This will help guide clinicians in selecting the appropriate pain management in this patient group.

Comparison of Drug-Assisted Tracheal Intubation Using Benzodiazepines and Induction Agents for First-Pass Intubation Success in Emergency Airway Management: A Retrospective Cohort Study

Objective: To determine first-pass intubation success between benzodiazepines and induction agents in adult patients who underwent drug-assisted intubation in the emergency department (ED). Materials and Methods: A retrospective chart review observational study collected the data of patients who underwent drug-assisted intubation in the ED of a university teaching hospital between January 1, 2021 and August 31, 2022. Two hundred seven patients were enrolled in the present study. The benzodiazepine and induction agent groups were compared in terms of baseline characteristics, and clinical management. Each benzodiazepine and induction agent were compared in first-pass intubation success, time to intubation success, adverse events, and 24-hour mortality. Results: Of the 207 patients included in the present study, 35 patients used benzodiazepine, and 172 patients used induction agents. The two groups had no differences in baseline characteristics. The first-pass intubation success rate was not significantly different among the medications with 90% in nine diazepam patients, 92% in 23 midazolam patients, 89.8% in 79 etomidate patients, and 94% in 79 propofol patients (p=0.553). Complications associated with intubation included hypotension, desaturation, tachycardia, bradycardia, arrhythmia, cardiac arrest, and pneumonia. No differences in 24-hour survival were observed. Conclusion: The sedative medications used during drug-assisted intubation should be chosen based on patient comorbidities and characteristics, as well as physician preferences and experiences. There were no differences between the benzodiazepine and induction agent groups in terms of first-pass intubation success, adverse events, or 24-hour survival. The use of benzodiazepines in settings with limited resources may be considered.

The Role of Propofol in Alcohol Withdrawal Syndrome: A Systematic Review.

The objective of this review was to evaluate the efficacy and safety of propofol in the treatment of critically ill patients diagnosed with alcohol withdrawal syndrome (AWS). A review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria, and Embase, MEDLINE (PubMed), Cochrane CENTRAL, and Web of Science were queried for results through June 2024. Studies providing efficacy or safety data associated with propofol with a reported diagnosis of AWS in critically ill patients were included. Studies evaluating pediatric patients, those without quantitative and qualitative outcome data, and those not readily translatable to English were excluded. Five retrospective cohort analyses of 218 patients were included in this systematic review. Patients were found to have both significant and non-significant increases in time to resolution of AWS symptoms when treated with propofol versus the AWS standard of care. Adjunct treatment with propofol was generally associated with reductions in total benzodiazepine use and increases in both ICU length of stay and duration of mechanical ventilation. The results of this systematic review provide the evidence necessary to support the use of propofol as an efficacious and safe medication in the management of severe and refractory AWS. Further investigation is required to determine optimal dosing strategies and durations of therapy. The results of this systematic review demonstrate the clinical utility of propofol as part of the management strategy for severe and refractory AWS.

Associations of benzodiazepine use with cognitive ability and age-related cognitive decline.

It remains uncertain whether long-term use of benzodiazepines is associated with age-related cognitive decline, and if cognitive ability in early life is the driver of any association. This study examines the association of cognitive ability in young adulthood with later use of benzodiazepines and explores whether the use of benzodiazepines during adult life is associated with cognitive decline in late midlife. The study samples include cognitive tests on the Børge Priens Prøve (BPP) from the conscription board examination (age 19 years) from 335 513 men born 1949-1961 and data from re-examinations of 5183 men 44 years later. Cognitive decline was defined as the difference between scores at the conscription board and the re-examination. Information on purchases of benzodiazepines was obtained from the Danish National Prescription Registry, 1995-2022. Associations were analysed using Cox proportional hazards and linear regression. In total, 120 911 (36%) men purchased benzodiazepines during a follow-up of 20 years. Lower cognitive scores in young adulthood were associated with a higher risk of initiating benzodiazepines (hazard ratio [95% CI] = 0.71[0.68-0.75]). Men with the highest cumulative use of benzodiazepines had larger cognitive decline (β-coefficient [95% CI] = -1.66 [-2.09 to -1.23] BPP scores) compared with never users. Current benzodiazepine users showed a larger cognitive decline than never users (β-coefficient [95% CI] = -2.42[-3.18 to -1.66] BPP scores) and this partially explained the above association. These estimates for cognitive decline were relatively small and may lack clinical relevance. Low cognitive ability increases the risk of benzodiazepine use in adulthood and cognitive decline is more pronounced in those with the highest benzodiazepine use compared with never-use, but the difference lacks clinical significance.

Incidence of Benzodiazepine Use and Misuse Among Adults in Selected Areas of Bangladesh

Background: Benzodiazepines (BDZ) are widely prescribed for anxiety and insomnia in Bangladesh, but their misuse has become a major public health concern. Objective: The aim of this study was to identify the incidence and patterns of use and misuse of BDZ in Bangladesh, and to explore the factors contributing to their misuse. Methodology: A cross-sectional study, including 368 current BDZ users, was conducted in the department of Pharmacology, Monno Medical College, Manikganj, during January, 2021 to December, 2022. The participants were selected randomly. Structured questionnaires were used to include participants’ personal information, drug use characteristics, physiological and psychological effects of drugs usage. Verbal consent was taken from each of the respondents. Results: In this study, 268(72.83%) of the participants were male, where 157(42.66%) were from the age group 31-40 years and 139(37.77%) were single. Among the study population, 51(13.86%) were students, 79(21.47%) had monthly family income above 50,000 Bangladeshi taka. Many of the participants reported that they used BDZs to relieve stress/pressure (108, 29.35%), followed by 95(25.82%) to manage insomnia, 79(21.47%) for relieving anxiety, depression and to get pleasure and others The mostly used drug was clonazepam (112, 30.43%), followed by diazepam (108, 29.35%) and others. Most of the users were influenced by friends (115, 31.25%). The common side effects of using BDZs were confusion (47, 12.77%), fatigue (45, 12.22%), drowsiness (37, 10.05%), and others. The mostly experienced withdrawal effect was headache (86, 23.28%), followed by insomnia (59, 16.25%), confusion (50, 13.48%) and others. Conclusion: BZDs were widely used in selected areas of Bangladesh with high incidence of misuse. The most common reason of misuse was self-medication. Increasing awareness program should be taken for safe and effective use of the drug. Journal of Monno Medical College December, 2023; 9 (2):68-72

Engagement in substance use disorder treatment after an emergency department visit among persons at high risk of opioid overdose: A prediction analysis

BackgroundCertified peer recovery specialists (CPRS) and licensed clinical social workers (LCSWs) can facilitate substance use disorder (SUD) treatment engagement for emergency department (ED) patients at risk for overdose. Predictors of treatment engagement after such behavioral services are unknown. MethodsThis secondary analysis included Rhode Island ED patients at high risk for opioid overdose participating in a randomized controlled trial comparing the effectiveness of CPRS and LCSWs services (2018–2021). SUD treatment engagement within 90 days post-discharge was identified using statewide administrative data. Potential predictors were obtained from baseline questionnaires. Classification and regression trees (CART) were used to identify predictors of treatment engagement. ResultsIn the ED, 323 and 325 participants received CPRS and LCSWs services, respectively, among whom 141 (43.7 %) and 137 (42.2 %) engaged in SUD treatment within 90 days post-discharge. For the CPRS group, predictors of treatment engagement included unhealthy alcohol use, prescription opioid or benzodiazepine use in past 6 months, and lifetime history of: unstable housing, barriers to treatment, bipolar disorder diagnosis, addiction treatment, and recovery services. In the LCSW group, predictors included health insurance, current pain, opioid overdose in past year, and lifetime history of anxiety disorder diagnosis and mental illness treatment. However, CART had low predictive accuracy (CPRS: 60.9 %, LCSW: 54.8 %). ConclusionsAmong ED patients at high risk of opioid overdose receiving behavioral services, 90-day SUD treatment engagement was high. Sociobehavioral and clinical patient characteristics did not accurately predict treatment engagement. Behavioral services should be offered to all ED patients at high risk of opioid overdose.

Medication Changes Among Older Drivers Involved in Motor Vehicle Crashes

Although older adults may use potentially driver-impairing (PDI) medications that can produce psychomotor impairment, little is known about changes to PDI medication use among older adults from the time before to the time after a motor vehicle crash (MVC). To quantify use of and changes in PDI medications among older adults before and after an MVC. This cohort study used linked Medicare claims and police-reported MVC data on 154 096 person-crashes among 121 846 older drivers. Eligible persons were drivers aged 66 years or older, involved in a police-reported MVC in New Jersey from May 1, 2007, through December 31, 2017, and with continuous enrollment in Medicare fee-for-service Parts A and B for at least 12 months and Part D for at least 120 days prior to the MVC. Data were analyzed from January 2022 to May 2024. Use of benzodiazepines, nonbenzodiazepine hypnotics, opioid analgesics, and other PDI medications in the 120 days before and 120 days after the MVC. Because each person could contribute multiple MVCs during the study period if they met eligibility criteria, the unit of analysis was the number of person-crashes. The proportion of person-crashes after which PDI medications were started, discontinued, or continued was quantified as well. Among 154 096 eligible person-crashes, the mean (SD) age of the drivers was 75.2 (6.7) years at the time of the MVC. Of 121 846 unique persons, 51.6% were women. In 80.0% of the person-crashes, drivers used 1 or more PDI medications before the crash, and in 81.0% of the person-crashes, drivers used 1 or more PDI medications after the crash. Use of benzodiazepines (8.1% before the crash and 8.8% after the crash), nonbenzodiazepine hypnotics (5.9% before the crash and 6.0% after the crash), and opioid analgesics (15.4% before the crash and 17.5% after the crash) was slightly higher after the MVC. After the MVC, drivers in 2.1% of person-crashes started benzodiazepines and 1.4% stopped benzodiazepines, drivers in 1.2% of person-crashes started nonbenzodiazepine hypnotics and 1.2% stopped nonbenzodiazepine hypnotics, and drivers in 8.4% of person-crashes started opioid analgesics and 6.3% stopped opioid analgesics. This cohort study suggests that most older drivers involved in MVCs did not use fewer PDI medications after crashes than before crashes. Qualitative research of perceived risks vs benefits of PDI medications is necessary to understand the reasons why MVCs do not appear to motivate clinicians to deprescribe PDI medications as a strategy to avert potential harms, including additional MVCs.

Association between Drug Use and Perception of Mental Health in Women Diagnosed with Fibromyalgia: An Observational Study.

Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and mental health issues. It affects approximately 1.78% of the general population; an estimated 4:1 ratio between women and men is observed. It significantly impacts quality of life and carries both clinical and social stigma. This study aims to evaluate the relationship between drug use and mental health in female patients with fibromyalgia. This study is prospective, observational, and cross-sectional. A questionnaire was administered to 544 subjects, achieving a representative sample size from a population of 800,000 subjects by using an algorithm for proportion estimation with a known sampling frame. The selection was non-random, making the sampling non-probabilistic. Logistic regression models were applied to assess the effect of drug use on perception of mental health; presence of symptoms such as comprehension and memory problems, insomnia, depression, and anxiety; and severity of cognitive symptoms and non-restorative sleep. To quantify the impact, odds ratios and confidence intervals have been observed. The findings indicate the non-recommended use of medications and reveal the ineffectiveness and adverse effects of drug interactions on mental health. The use of benzodiazepines and sedative-hypnotics is significantly associated with a negative perception of mental health. Benzodiazepines do not improve symptoms or significantly reduce their severity. SSRI antidepressants do not enhance mental health perception; however, when used exclusively, they are effective in reducing the severity, but not the prevalence, of cognitive symptoms. The results highlight the complexity of pharmacological management in FM and raise concerns about the inappropriate use of ineffective or counterproductive drug interactions affecting patients' mental health. They underscore the need for multidisciplinary and personalized strategies that include close and careful monitoring, as well as the simultaneous use of non-pharmacological treatments that have demonstrated evidence in improving quality of life without negatively affecting mental health, such as patient education, psychological therapy, physiotherapy, and mindfulness.