Non-benzodiazepine Hypnotics Research Articles

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.

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

Background: 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. Objective: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS. Methods: 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. Results: 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. Conclusion: The prevalence of CNS-active polypharmacy has increased among people with MS with a growing disparity by sex.

Non-benzodiazepine Hypnotics and Police-Reported Motor Vehicle Crash Risk among Older Adults: A Sequential Target Trial Emulation.

Non-benzodiazepine hypnotics ( "Z-drugs") are prescribed for insomnia, but might increase risk of motor vehicle crash (MVC) among older adults through prolonged drowsiness and delayed reaction times. We estimated the effect of initiating Z-drug treatment on the 12-week risk of MVC in a sequential target trial emulation. After linking New Jersey driver licensing and police-reported MVC data to Medicare claims, we emulated a new target trial each week (July 1, 2007 - October 7, 2017) in which Medicare fee-for-service beneficiaries were classified as Z-drug-treated or untreated at baseline and followed for an MVC. We used inverse probability of treatment and censoring weighted pooled logistic regression models to estimate risk ratios (RR) and risk differences with 95% bootstrap confidence limits (CLs). There were 257,554 person-trials, of which 103,371 were Z-drug-treated and 154,183 untreated, giving rise to 976 and 1,249 MVCs, respectively. The intention-to-treat RR was 1.06 (95%CLs 0.95, 1.16). For the per-protocol estimand, there were 800 MVCs and 1,241 MVCs among treated and untreated person-trials, respectively, suggesting a reduced MVC risk (RR 0.83 [95%CLs 0.74, 0.92]) with sustained Z-drug treatment. Z-drugs should be prescribed to older patients judiciously but not withheld entirely over concerns about MVC risk.

A Nationwide Emergency Department Data Analysis to Predict Beers List Medications Use Among Older Adults

BackgroundThe use of potentially inappropriate medications (PIMs) is considered an important quality indicator for older adults seen in the ambulatory care setting. Study ObjectivesTo evaluate the pattern of potentially inappropriate medication (PIMs) use as specified in the Beers Criteria, for older adults during emergency department (ED) visits in the United States. MethodsUsing data from the National Hospital Ambulatory Care Survey (NHAMCS) we identified older adults (age 65 or older) discharged home from an ED visit in 2019. We defined PIMs as those with an ‘avoid’ recommendation under the American Geriatrics Society (AGS) 2019 Beers Criteria in older adults. Logistic regression models were used to assess demographic, clinical, and hospital factors associated with the use of any PIMs upon ED discharge. ResultsOverall, 5.9% of visits by older adults discharged from the ED included administration or prescriptions for PIMs. Among those who received any PIMs, 25.5% received benzodiazepines, 42.5 % received anticholinergics, 1.4% received nonbenzodiazepine hypnotics, and 0.5% received barbiturates. A multivariable model showed statistically significant associations for age 65 to 74 (OR 1.91, 95% CI 1.39–2.62 vs. age >=75), dementia (OR 0.45, 95% CI 0.21–0.95), lower immediacy (OR 2.45, 95% CI 1.56–3.84 vs. higher immediacy), and Northeastern rural region (OR 0.34, 95% CI 0.21–0.55 vs. Midwestern rural). ConclusionWe found that younger age and lower immediacy were associated with increased prescriptions of PIMs for older adults seen, while dementia and Northeastern rural region was associated with reduced use of PIMs seen and discharged from EDs in United States.

Psychiatric comorbidities and prescribing tendencies of sleep medications and related medications in young people with insomnia: a United States commercial claims-based analysis.

To characterize children and youth newly diagnosed with insomnia and to describe their use of sleep and other related prescription medications. Within a commercial claims database (January 1, 2016-December 31, 2021), we identified children and youth (2-24 years) with a newly recorded insomnia diagnosis (G47.0x; F51.0x) and examined psychiatric diagnoses in the prior 6 months. We evaluated sleep and related prescription medications dispensed in the week after new insomnia diagnoses (i.e. trazodone, other antidepressants, hydroxyzine, alpha-agonists, benzodiazepines, non-benzodiazepine hypnotics "z-drugs," antipsychotics, and others). Analyses were stratified by age and psychiatric comorbidities. Among 68 698 children and 108 118 older youth (18-24 years) with a new insomnia diagnosis, three-quarters had a diagnosed comorbid psychiatric condition; anxiety disorders, depression, and ADHD were the most common. Among those without comorbid psychiatric diagnoses, 20.2% of children and 37.4% of older youth had a sleep or related medication dispensed in the following week. In children without a comorbid psychiatric diagnosis, alpha-agonists, hydroxyzine, and trazodone were the most common medications; in older youth, trazodone was the most common medication followed by hydroxyzine, z-drugs, and SSRIs. Sleep and related prescription medications were more commonly dispensed to those with psychiatric comorbidities. From 2017 to 2021, there was an increase in hydroxyzine prescriptions following a new insomnia diagnosis and decline in z-drug and benzodiazepine prescriptions. Our findings from a nationwide sample of young people with insomnia highlight the high prevalence of psychiatric comorbidities and variety of sleep and related medications they receive. Characterizing prescribing tendencies informs guideline development and future research.

The Intersection of Insomnia Disorder and Major Depressive Disorder: A Clinical Perspective

Major depressive disorder (MDD) is associated with profound sleep architectural alterations including reduced slow wave activity, increased delta sleep ratio, REM sleep disinhibition, shortened REM onset latency, and increased REM density. Antidepressants, though mitigating depressive symptoms, often disrupt sleep patterns, highlighting the delicate balance between treatment benefits and sleep-related impacts. Comprehensive assessment and management of insomnia is pivotal due to its significant implications for effective clinical management and treatment outcomes in MDD. Nonpharmacological treatments, notably cognitive-behavioral therapy for insomnia (CBTi), and digital CBTi (dCBTi) should be considered. CBTi unravels maladaptive sleep beliefs and behaviors, yielding improvements in both insomnia and MDD symptoms. Digital CBTi platforms extend accessibility, offering potential relief to a broader demographic. Sedating antidepressants, nonbenzodiazepine hypnotics, and atypical antipsychotics address insomnia within MDD, with cautious consideration for side effects. A combination of pharmacotherapy with CBTi might yield augmented outcomes in patients with MDD and comorbid insomnia. Ketamine, electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagal nerve stimulation (VNS), and deep brain stimulation (DBS) explore novel dimensions in treating treatment-resistant depression, potentially influencing sleep disruptions. [ Psychiatr Ann . 2023;53(11):502–507.]

Treatment of insomnia in myasthenia gravis-A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia.

This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia. This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4-5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication. A total of 75 MG patients with insomnia were included in this study. After 4-5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders. Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment.

Coprescribing of opioids and psychotropic medications among Medicare-enrolled older adults on long-term opioid therapy

BackgroundPressures to reduce opioid prescribing have potential to incentivize coprescribing of opioids (at lower dose) with psychotropic medications. Evidence concerning the extent of the problem is lacking. This study assessed trends in coprescribing and characterized coprescribing patterns among Medicare-enrolled older adults with chronic noncancer pain (CNCP) receiving long-term opioid therapy (LTOT). MethodsA cohort study was conducted using 2012-2018 5% National Medicare claims data. Eligible beneficiaries were continuously enrolled and had no claims for cancer diagnoses or hospice use, and ≥ 2 claims with diagnoses for CNCP conditions within a 30-day period in the 12 months before the index date (LTOT initiation). Coprescribing was defined as an overlap between opioids and any class of psychotropic medication (antidepressants, benzodiazepines, antipsychotics, anticonvulsants, muscle relaxants, and nonbenzodiazepine hypnotics) based on their prescription fill dates and days of supply in a given year. The occurrence of coprescribing, coprescribing intensity, and number of days of overlap with psychotropic medications were calculated for each calendar year. ResultsThe eligible study population of individuals on LTOT ranged from 2038 in 2013 to 1751 in 2018. The occurrence of coprescribing among eligible beneficiaries decreased from 73.41% in 2013 to 70.81% in 2015 and then increased slightly to 71.22% in 2018. Among eligible beneficiaries with at least one overlap day, the coprescribing intensity with any class of psychotropic medications showed minimal variation throughout the study period: 74.73% in 2013 and 72.67% in 2018. Across all the years, the coprescribing intensity was found to be highest with antidepressants (2013, 49.90%; 2018, 50.33%) followed by benzodiazepines (2013, 25.42%; 2018, 19.95%). ConclusionCoprescribing was common among older adults with CNCP who initiated LTOT but did not rise substantially in the period studied. Future research should investigate drivers behind coprescribing and safety of various patterns of use.

The outcome of using zolpidem for treatment of postoperative posterior fossa syndrome in children with brain tumor

Abstract Introduction: At present, there is no supporting evidence-based therapy of proven efficacy to treat posterior fossa syndrome (PFS) after surgical resection of posterior fossa tumors in children where only 22% of patients may experience a full recovery. However, zolpidem, a nonbenzodiazepine hypnotics drug, seems to be a possible treatment option for PFS symptoms. Methods and Materials: This was a retrospective chart review for all children with brain tumors younger than 15 years diagnosed with confirmed PFS after surgical resection at King Abdulaziz Medical City, Jeddah, and received zolpidem to alleviate the PFS symptoms between May 2016 and April 2019. Results: A total of 6 pediatric patients who experienced PFS symptoms (median of 4 days, range 1–7 days) were included. The most commonly observed symptoms were irritability, hypotonia, swallowing deficit, unsteady walking, and delayed speech. To alleviate the PFS symptoms, zolpidem was commenced 2–5 days postoperatively. The median duration of use was 13.5 days. During the hospital course, recovery of speech was observed after 2 weeks in most patients (50%) while 83.3% of patients recovered their normal speech in 4 months although not fully ambulated. No discontinuation of zolpidem use was reported because of adverse events. Conclusion: Most of our children (83.3%) who experienced PFS postresection responded to zolpidem trials which may represent a promising research field.

Systematic assessment of non-medical use of prescription drugs using doctor-shopping indicators: A nation-wide, repeated cross-sectional study.

The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the same drug) during 10years for more than 200 psychoactive prescription drugs in the 67 million inhabitants in France. This was a nation-wide, repeated cross-sectional study. Data are from the French National Health Data System in 2010, 2015 and 2019 for 214 psychoactive prescription drugs (i.e. anaesthetics, analgesics, antiepileptics, anti-Parkinson drugs, psycholeptics, psychoanaleptics, other nervous system drugs and antihistamines for systemic use). The detection and quantification of doctor-shopping relied upon an algorithm that detects overlapping prescriptions from repeated visits to different physicians. We used two doctor-shopping indicators aggregated at population level for each drug dispensed to more than 5000 patients: (i) the quantity doctor-shopped, expressed in defined daily doses (DDD), which measures the total quantity doctor-shopped by the study population for a given drug; and (ii) the proportion doctor-shopped, expressed as a percentage, which standardizes the quantity doctor-shopped according to the use level of the drug. The analyses included approximately 200 million dispensings to approximately 30 million patients each year. Opioids (e.g. buprenorphine, methadone, morphine, oxycodone and fentanyl), benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) (e.g. diazepam, oxazepam, zolpidem and clonazepam) had the highest proportions doctor-shopped during the study period. In most cases, the proportion and the quantity doctor-shopped increased for opioids and decreased for benzodiazepines and Z-drugs. Pregabalin had the sharpest increase in the proportion doctor-shopped (from 0.28 to 1.40%), in parallel with a sharp increase in the quantity doctor-shopped (+843%, from 0.7 to 6.6DDD/100 000 inhabitants/day). Oxycodone had the sharpest increase in the quantity doctor-shopped (+1000%, from 0.1 to 1.1DDD/100 000 inhabitants/day), in parallel with a sharp increase in the proportion doctor-shopped (from 0.71 to 1.41%). Detailed results for all drugs during the study period can be explored interactively at: https://soeiro.gitlab.io/megadose/. In France, doctor-shopping occurs for many drugs from many pharmacological classes, and mainly involves opioid maintenance drugs, some opioids analgesics, some benzodiazepines and Z-drugs and pregabalin.

High Prescribing and State-Level Variation in Z-Drug Use Among Medicare Patients.

Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance; these drugs increase the risk of fall-related injuries in older adults. The American Geriatrics Society's Beers criteria classifies Z-drugs as high-risk and strongly recommends avoiding prescribing Z-drugs to older adults due to adverse effects. The study objectives were to determine the prevalence of Z-drug prescribing among Medicare Part D patients and identify state or specialty-dependent prescribing differences. This study also aimed to determine prescribing patterns of Z-drugs to Medicare patients. Z-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions per provider within each specialty was also determined. Zolpidem was the most prescribed Z-drug (95.0%). Prescriptions per 100 enrollees were significantly high in Utah (28.2) and Arkansas (26.7) and significantly low in Hawaii (9.3) relative to the national average (17.5). Family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly high among psychiatrists. Contrary to the Beers criteria, Z-drugs are prescribed to older adults at high rates.

Optimising the prescribing of drugs that may cause dependency: An evidence and gap map of systematic reviews.

We set out to map the quantitative and qualitative systematic review evidence available to inform the optimal prescribing of drugs that can cause dependency (benzodiazepines, opioids, non-benzodiazepine hypnotics, gabapentinoids and antidepressants). We also consider how this evidence can be used to inform decision-making in the patient care pathway for each type of medication. Eight bibliographic databases were searched for the period 2010 to 2020. All included reviews were initially appraised using four items from the Collaboration for Environmental Evidence Synthesis Assessment Tool, with reviews that scored well on all items proceeding to full quality appraisal. Key characteristics of the reviews were tabulated, and each review was incorporated into an evidence and gap map based on a patient care pathway. The care pathway was based upon an amalgamation of existing NICE guidelines and feedback from clinical and patient stakeholders. We identified 80 relevant reviews and displayed them in an evidence and gap map. The evidence included in these reviews was predominantly of low overall quality. Areas where systematic reviews have been conducted include barriers and facilitators to the deprescribing of drugs that may cause dependency, although we identified little evidence exploring the experiences or evaluations of specific interventions to promote deprescribing. All medications of interest, apart from gabapentinoids, were included in at least one review. The evidence and gap map provides an interactive resource to support (i) policy developers and service commissioners to use evidence in the development and delivery of services for people receiving a prescription of drugs that may cause dependency, where withdrawal of medication may be appropriate, (ii) the clinical decision-making of prescribers and (iii) the commissioning of further research. The map can also be used to inform the commissioning of further systematic reviews. To address the concerns regarding the quality of the existing evidence based raised in this report, future reviews should be conducted according to best-practice guidelines. Systematic reviews focusing on evaluating interventions to promote deprescribing would be particularly beneficial, as would reviews focusing on addressing the paucity of evidence regarding the deprescription of gabapentinoids.

Prevalence and correlates of the misuse of z-drugs and benzodiazepines in the National Survey on Drug Use and Health.

Benzodiazepines and non-benzodiazepine hypnotics (z-drugs) are commonly prescribed for their anxiolytic and hypnotic properties, though they can also be misused. In studies examining the epidemiology of prescription drug misuse, these medication classes are commonly combined, rendering inadequate knowledge of their patterns of misuse. The objective of this study was to characterize the population prevalence, conditional dependence, and sociodemographic and clinical correlates of the misuse of benzodiazepines and z-drugs. Data from the National Survey on Drug Use and Health from 2015 to 2019 were used to estimate population-level prevalence and characteristics of benzodiazepine and z-drug misuse. Groups were derived based on past-year misuse of benzodiazepines alone, z-drugs alone, or both drug types. Unadjusted regression analyses were used to compare groups on characteristics of interest. Exposure to benzodiazepines and/or z-drugs via prescription or misuse was common; however, only 2% of the population was estimated to have misused a benzodiazepine in the past year, and less than 0.5% misused z-drugs. People who misused only z-drugs were generally older, more likely to have health insurance, more educated, and had less severe psychiatric symptoms. This group was also more likely to report misuse to cope with sleep difficulty. Although concurrent substance use was highly prevalent in all groups, people who misused z-drugs alone generally reported less concurrent substance use than the other groups. The misuse of z-drugs is less common than benzodiazepines, and people who misuse only z-drugs appear to generally have lower clinical severity. Nonetheless, a substantial subgroup of people exposed to z-drugs report concurrent, past-year use of other substances. Further research on z-drug misuse, including consideration of whether it should be grouped with other anxiolytic/hypnotic drugs, is needed.

Comparative Risk of Harm Associated with Zopiclone or Trazodone Use in Nursing Home Residents: a Retrospective Cohort Study in Alberta, Canada.

There is growing evidence of harm associated with trazodone and nonbenzodiazepine sedative hypnotics (e.g., zopiclone); however, their comparative risk of harm is unknown. We conducted a retrospective cohort study with linked health administrative data, which enrolled older (≥66 years old) nursing home residents living in Alberta, Canada, between December 1, 2009, and December 31, 2018; the last follow-up date was June 30, 2019. We compared the rate of injurious falls and major osteoporotic fractures (primary outcome) and all-cause mortality (secondary outcome) within 180 days of first prescription of zopiclone or trazodone with cause-specific hazard models and inverse probability of treatment weights to control for confounding; primary analysis was intention-to-treat and secondary analysis was per-protocol (i.e., residents censored if dispensed the other exposure drug). Our cohort included 1,403 residents newly dispensed trazodone and 1,599 residents newly dispensed zopiclone. At cohort entry, the mean resident age was 85.7 (standard deviation [SD] 7.4), 61.6% were female, and 81.2% had dementia. New zopiclone use was associated with similar rates of injurious falls and major osteoporotic fractures (intention-to-treat-weighted hazard ratio 1.15, 95% confidence interval [CI] 0.90-1.48; per-protocol-weighted hazard ratio 0.85, 95% CI 0.60-1.21) and all-cause mortality (intention-to-treat-weighted hazard ratio 0.96, 95% CI 0.79-1.16; per-protocol-weighted hazard ratio 0.90, 95% CI 0.66-1.23) compared to trazodone. Zopiclone was associated with a similar rate of injurious falls, major osteoporotic fractures, and all-cause mortality compared to trazodone-suggesting one medication should not be used in lieu of the other. Appropriate prescribing initiatives should also target zopiclone and trazodone.

Long-Term Use of Insomnia Medications: An Appraisal of the Current Clinical and Scientific Evidence.

While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the evidence supporting the focus statement, "No insomnia medication should be used on a daily basis for durations longer than 3 weeks at a time". The panelists' assessment was also compared to findings from a national survey of practicing physicians, psychiatrists, and sleep specialists. Survey respondents revealed a wide range of opinions regarding the appropriateness of using the US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia lasting more than 3 weeks. After discussion of the literature, the panel unanimously agreed that some classes of insomnia medications, such as non-benzodiazepines hypnotics, have been shown to be effective and safe for long-term use in the appropriate clinical setting. For eszopiclone, doxepin, ramelteon and the newer class of dual orexin receptor antagonists, the FDA label does not specify that their use should be of a limited duration. Thus, an evaluation of evidence supporting the long-term safety and efficacy of newer non-benzodiazepine hypnotics is timely and should be considered in practice recommendations for the duration of pharmacologic treatment of chronic insomnia.

Identifying barriers and facilitators to deprescribing benzodiazepines and sedative hypnotics in the hospital setting using the Theoretical Domains Framework and the Capability, Opportunity, Motivation and Behaviour (COM-B) Model: a qualitative study

ObjectivesGeriatric guidelines strongly recommend avoiding benzodiazepines and non-benzodiazepine sedative hypnotics in older adults. Hospitalisation may provide an important opportunity to begin the process of deprescribing these medications, particularly as new...

Polypharmacy and medication related falls risk in orthogeriatric femoral fracture patients Polypharmacy and medication related falls risk in orthogeriatric femoral fracture patients

Aim: To reportpolypharmacy rates and identify specific medications that increase falls riskin orthogeriatric femoral fracture patients. Method: A retrospectivesub-analysis, using the electronic medical records of patients admitted with a minimaltrauma femoral fracture to a tertiary teaching hospital during a 12-monthperiod was undertaken. Specific medications associated with falls risk wereclassified under three specific groups: benzodiazepines, tricyclicantidepressants (TCAs), and non-benzodiazepine hypnotics. Results: A sample of 131patients was included in the audit. Of these, 99 patients (75.6%) were reportedto be taking five or more medications prior to their falls related admission.From this, 49 patients (37.4%) were taking ten or more medications. One in fivepatients were found to be taking specified falls risk medications prior toadmission, primarily benzodiazepines (75.8%). Conclusion: Orthogeriatricpatients admitted to hospital with a femoral fracture following a minimaltrauma fall were commonly taking five or more medications prior to admission.Over a third of patients that were reported to take ten or more pre-admissionmedications were taking specified falls risk medications. This highlights theneed for medication-reviews and de-prescribing, particularly focusing on fallsrisk medications, to reduce incidence of falls and minimal trauma fractures inhigh risk patients

Use of Benzodiazepines and Z-Drugs in Multiple Sclerosis.

ObjectiveUse of benzodiazepines and Z-drugs (non-benzodiazepine sedative hypnotics) is controversial due to adverse health outcomes in the general population. However, little is known about their use in people with multiple sclerosis (MS). We estimated the incidence and prevalence of benzodiazepine and Z-drug use (jointly BZD) in the MS population as compared to an age-, sex- and geographically-matched population without MS, and examined the association of mood/anxiety disorders with the use of BZD over a twenty-year period.MethodsUsing administrative data from Manitoba, Canada, we identified 2,985 persons with incident MS and 14,891 persons without MS matched 5:1 on sex, birth year and region. We applied validated case definitions to identify persons with any mood/anxiety disorder. Dispensations of BZD were identified. To assess the association between MS, mood/anxiety disorders and BZD use we constructed generalized linear models adjusting for age, sex, index year, socioeconomic status, urban/rural residence, physical comorbidities, and health care use. We also examined patterns of BZD use.ResultsIn 2016, the crude incidence of benzodiazepine use in the MS cohort was 2.10% (95%CI: 1.43–2.98%), 1.49-fold higher than in the non-MS cohort (1.41%; 95%CI: 1.18–1.67%). The crude incidence of Z-drug use in the MS cohort was 1.77% (95%CI: 1.20–2.51%), 1.78-fold higher than in the non-MS cohort (0.99%; 95%CI: 0.81–1.21%). After adjusting for covariates, among individuals without an active mood/anxiety disorder, the MS cohort had a 39% increased incidence rate of benzodiazepine use and a 72% increased incidence rate of Z-drug use as compared to the non-MS cohort. Among individuals with an active mood/anxiety disorder, the incidence of BZD use did not differ between the MS and non-MS cohorts. A higher proportion of people with MS used BZD for ≥6 months than people without MS.ConclusionUse of BZD is more common in people with MS than in general population controls, and use of these agents is in persons with MS is often chronic.

The Tolerance and Dependence of Zolpidem, Not a ‘So Safe’ Drug?

Zolpidem is a short-acting non-benzodiazepine hypnotics and has a short elimination half-life that was introduced in the 1980s. It has an favorable and safe profile compared to short-acting benzodiazepines (BZD), so it was expected that the disadvantages of BZD, such as sedation the next day and daytime sleepiness, as well as dependence and withdrawal symptoms, could be overcome. However, there is a growing body of case reports on zolpidem abuse and dependence, as well as withdrawal syndrome and epileptic seizures related to zolpidem discontinuation. Many subsequent studies have revealed that increasing concentrations of zolpidem result in loss of receptor selectivity, and binds to other subunits of the GABA-A receptor, similar to benzodiazepine. Nevertheless, zolpidem is one of the most commonly prescribed hypnotics in Korea, and related abuse and dependence cases are increasing. Thus, it is necessary to understand the developing mechanism of abuse and dependence related zolpidem, and be prepared with strategies to detoxify or intervene in any related condition.

Overdose deaths involving non-BZD hypnotic/sedatives in the USA: Trends analyses

There is sparse knowledge on overdose deaths resulting from non-benzodiazepines and gabapentinoids usage. We examined overdose death rate across demographics categories and the overdose death trends over time. Using data from the National Center for Health Statistics (USA), we identified 21,167 persons that died with an overdose ICD code as the underlying cause of death and had a T42.6/T42.7 ICD code, which include gabapentinoids and z-drugs, among their multiple causes of death. The overdose death rate was calculated per 100,000 persons for every year between 2000 and 2018. We used joinpoint regression analyses to assess trends over time. We identified a rise in the proportion of deaths with a T42.6/T42.7 ICD code between 2000 and 2006 (yearly change: +0.06) and between 2006 and 2015 (yearly change: +0.32). From 2000 to 2008, the proportion of deaths with any other T code rose significantly (yearly change: +3.56). Between 2008 and 2018, there was also a significant rise (yearly change: +1.31). From 2000 to 2015, the proportion of deaths with a T42.6/T42.7 ICD code with any other T code rose (yearly change: +2.58). From 2000 to 2015, the proportion of deaths with a T42.6/T42.7 ICD code with a concurrent benzodiazepine T code rose (yearly change: +1.98). From 2000 to 2005, the proportion of alcohol T codes rose non-significantly (yearly change: +0.35). Finally, the proportion of alcohol T codes fell significantly between 2008 and 2018 (yearly change: - 0.74). Deaths due to non-benzodiazepine hypnotics and gabapentinoids increased significantly over the last two decades. Clinicians should not assume that replacing benzodiazepines and opioids with these medications necessarily lowers risk to the patient. This study was funded by an internal grant from the Columbia University President's Global Innovation Fund (PI: Martins).