Benzodiazepine Prescriptions Research Articles

Evolution in the prescription and cost of non-intravenous rescue benzodiazepines for the treatment of seizure emergencies.

The proportion of patients with epilepsy who have a non-intravenous rescue benzodiazepine (non-IV-rBZD) available for seizure emergencies is unknown. This study aims to describe prescription patterns from 2006 to 2022, factors associated with prescription, and the impact of recently introduced intranasal benzodiazepines on prescription and cost. Retrospective analysis of the MarketScan Database, a claims database of privately insured patients in the United States. Among 213 384 patients (53% female, median (p25-p75) age: 33 (17-50) years) with epilepsy taking long-term anti-seizure medications with follow-up of 2.62 (1.54-4.73) years, only 30 371 patients (14.2%) had at least one non-IV-rBZD prescription. The proportion of patients with at least one non-IV-rBZD prescription was higher among: (1) younger patients (61.4% in the 0-5 year age group, 44.2% in the 6-12 year age group, 23.9% in the 13-21 year age group, 4.8% in the 22-35 year age group, 1.8% in the 36-50 year age group, 1.3% in the 51-60 year age group, and 1.0% in the older than 60 years age group); (2) patients with refractory epilepsy (24.3% vs 10.9% in non-refractory epilepsy); and (3) patients with more emergency department visits or hospital admissions for epilepsy (7.1% among patients with 0, 19.2% among patients with 1-3, and 31.1% among patients with more than 3). Multivariate analysis confirmed young age, refractory epilepsy, and emergency department visits or hospitalizations for epilepsy as strong independent predictors of having at least one non-IV-rBZD prescription. Prescriptions for intranasal midazolam and intranasal diazepam have increased rapidly; they had moderately increased the overall proportion of patients with a non-IV-rBZD prescription, whereas the inflation-adjusted cost of non-IV-rBZDs has markedly increased. The vast majority of patients with epilepsy have not filled a prescription for non-IV-rBZDs. Seizure emergency readiness can be markedly improved, especially among adults. The cost of non-IV-rBZDs has increased with intranasal rescue medications.

Impact of a System-Wide Clinician Educational Program on Benzodiazepine and Non-Benzodiazepine Sedative-Hypnotic Prescribing in an Integrated Health System

Impact of a System-Wide Clinician Educational Program on Benzodiazepine and Non-Benzodiazepine Sedative-Hypnotic Prescribing in an Integrated Health System

Increases in benzodiazepine prescribing for postpartum anxiety during COVID-19.

Postpartum mood disorders affect many women following childbirth. Prescribing medication for depression and anxiety is one strategy for the effective treatment of postpartum mood disorders. Left untreated, mothers experiencing these disorders and their infants face increased risks of adverse health outcomes. Little is known about how diagnosis and treatment of postpartum mood disorders changed during COVID-19. We used a retrospective pooled cross-sectional design in a sample of privately-insured postpartum women in U.S. claims data from January 1, 2016 to December 31, 2020. We measured changes in diagnoses of anxiety and depression and changes in prescription fills and days supplied of classes of medications used to treat these conditions (antidepressants, benzodiazepines, and z-drugs). We used ordinary least squares (OLS) regression for each outcome variable during the pre-pandemic period and forecast expected outcomes the observation period. Forecasted and actual values of the outcomes were then compared. Following the onset of the COVID-19 pandemic in March 2020, diagnoses of depression and anxiety were not significantly higher among privately insured postpartum women in the United States. The proportion of privately-insured postpartum women filling a benzodiazepine prescription increased by 15.2%. We find diagnosis of postpartum mood disorders did not increase after the onset of the COVID-19 pandemic, however, fills of benzodiazepines increased among privately-insured postpartum women. Given prior evidence of increased depressive and anxiety symptoms among postpartum women during COVID-19, this suggests increased barriers to appropriate diagnoses and treatment for depression during this period.

Concurrent Perioperative Benzodiazepine and Opioid Utilization in Opioid-Naive Patients Undergoing Soft Tissue Hand Surgery.

While concomitant opioid and benzodiazepine use is discouraged due to an increased risk of sedation/overdose, the extent of perioperative opioid utilization in hand surgery patients already using benzodiazepines is unknown. Using an administrative claims database, we identified adults undergoing carpal tunnel, DeQuervain, or trigger finger release, palmar fasciectomies, ganglion/mucoid cyst removals, and hand/wrist soft tissue mass excisions from 2011 to 2021. We identified opioid-naive patients with a benzodiazepine prescription within 90 days before surgery. Outcomes included the percentage of patients prescribed opioids and the amount of opioids prescribed, new persistent opioid utilization, postoperative emergency department (ED) visits, hand therapy utilization, and opioid overdose. We used multivariable regression models to adjust for age, sex, region, insurance, procedure, and comorbidities. Patients with benzodiazepine utilization had a higher adjusted odds of perioperative opioid prescriptions, amount of opioids filled, and new, persistent opioid use compared with patients without benzodiazepine use (all P < .001). In the multivariable analysis, patients with benzodiazepine use received +30.8 (95% CI: 28.9-32.8) morphine milligram equivalents and had an odds ratio of 1.48 (95% CI: 1.44-1.52) for developing new, persistent opioid use compared with patients without benzodiazepine use. Patients with preoperative benzodiazepine use also had increased postoperative ED visits and hand therapy utilization. Opioid-naive patients undergoing soft tissue hand surgery who are using benzodiazepines were prescribed opioids more frequently/at higher amounts and experienced an increased odds of developing new, persistent opioid use. Surgeons could consider reducing opioid prescriptions in patients already using benzodiazepines in favor of nonopioid pain strategies.

Nationwide trends in diagnosed sedative, hypnotic or anxiolytic use disorders in adolescents and young adults enrolled in Medicaid: 2001-2019.

Sedative, hypnotic or anxiolytic use disorders (SHA-UD) are defined by significant impairment or distress caused by recurrent sedative, hypnotic or anxiolytic use. This study aimed to measure trends in the prevalence of SHA-UD diagnoses in adolescent and young adult US Medicaid enrollees from 2001 to 2019. Annual, cross-sectional study, 2001-2019. Medicaid Analytic eXtracts (MAX) and Transformed Medicaid Analytic Files (TAF) from 42 US states with complete data. Adolescents (13-17 years) and young adults (18-29 years) with ≥10months Medicaid enrollment in the calendar year; analytic sample contained 5.7 (2001) to 13.2 (2019) million persons per year. Annual prevalence of SHA-UD in adolescent and young adult Medicaid enrollees [defined as an inpatient or outpatient ICD code (304.1x, 305.4x, F13.1x, F13.2x) in the calendar year] was stratified by sex, race/ethnicity, receipt of a benzodiazepine, z-hypnotic or barbiturate prescription, and selected mental health diagnoses. Absolute and relative percent-changes from 2001 vs. 2019 were summarized. Secondary analyses were restricted to states with more consistent data capture. The prevalence of SHA-UD diagnoses statistically significantly increased for adolescents (0.01% to 0.04%) and young adults (0.05% to 0.24%) from 2001 to 2019. Increasing trends were observed in sex and race/ethnicity subgroups, with greatest relative increases among Non-Hispanic Black (624%) and Hispanic (529%) young adults. The trend increased among those with and without a benzodiazepine, z-hypnotic or barbiturate prescription; i.e. young adults with (2001 = 0.39% to 2019 = 1.77%) and without (2001 = 0.03% to 2019 = 0.18%) a prescription. Most adolescents (76%) and young adults (91%) with a SHA-UD diagnosis in 2019 had a comorbid substance use disorder. Sedative, hypnotic or anxiolytic use disorders (SHA-UD) diagnoses increased 3- to 5-fold between 2001 and 2019 for adolescent and young adult US Medicaid enrollees, with prevalence remaining low in adolescents. The increase over two decades may be attributed to changes in the availability, use and misuse of sedative, hypnotic and anxiolytic medications and to increased detection, awareness and diagnosing of SHA-UD.

P1278 The use of pain and sedative medications among individuals with a diagnosis of Inflammatory Bowel Disease

Abstract Background Individuals with inflammatory bowel disease (IBD) frequently experience pain, poor sleep and anxiety even when disease activity is well controlled. A nationwide UK study showed that 42% individuals with IBD want help with pain and 56% want help with fatigue.(1) Unfortunately, pharmacological management of these symptoms is often inadequate and frequently associated with significant side effects, particularly when pain medications and sedatives are prescribed chronically or concurrently. Despite the risks, there is a lack of evidence regarding the trend in use of these medications in European IBD populations. Methods An extract of over 80,000 individuals with IBD was obtained from the general practice database "Clinical Practice Research Datalink" (CPRD) including details of prescriptions, diagnoses and demographics. Data from 1st January 2010 to 31st December 2019 was analysed to assess prescribing trends for opioids, gabapentinoids, benzodiazepines, and Z-drugs. We examined overall, chronic, and concurrent prescribing patterns. Chronic prescribing was defined as continuous use of opioids for more than 3 months, or Z-drugs and benzodiazepines for more than 4 weeks, in accordance with national guidelines.(2–4) Concurrent prescribing, assessed in 2-year intervals, was defined as overlapping prescriptions of opioids, gabapentinoids, Z-drugs, or benzodiazepines. Data were analysed using Stata 18 and R. Results Over the study period, the annual prevalence of gabapentinoids, and Z-drug use increased (2.5% to 5.5% and 3.3% to 3.4% respectively) while strong opioid (9.2%-8.5%), weak opioid (12.1%-9.9%) and benzodiazepine use (6.1%-5.6%) decreased (see Figure 1). The annual prevalence of chronically prescribed medications in 2019 were 2.5% strong opioids, 3.4% weak opioids, 2.4% benzodiazepines and 1.8% Z-drugs. Over 1 in 5 gabapentinoid prescriptions were concurrent with another pain or sedative medication; 17% with strong opioids, 6% benzodiazepines and 4% Z-drugs, while 18% of strong opioids, 18% Z-drugs and 18% benzodiazepines were concurrently prescribed with another pain medication or sedative (see Table 1). Conclusion Overall, prescribing rates of pain medications and sedatives in individuals with IBD remain concerning. While opioid use has dropped and sedative use is stable, gabapentinoid use has increased, and all are often co-prescribed. Chronic prescribing of these medications provides no clear benefit and poses significant risks. Future efforts should prioritise reducing chronic and concurrent prescribing of pain and sedative medications

Characterizing Difficulties and Management of Sleep Disturbances in a Tertiary Palliative Care Unit-A Retrospective Review.

Objective: Difficulty sleeping is common in palliative care, however often unrecognized by palliative care physicians. This retrospective review aims to gain a better understanding of the causes and treatment of sleeping disturbances in a tertiary palliative care unit. Methods: This study included 200 palliative care inpatients admitted between January 1, 2015, and August 31, 2020. Patients with sleep disturbances were placed into 3 subgroups: insomnia, delirium, and those with an unclear diagnosis. These categories were analyzed by bivariate analysis (ANOVA, Kruskal-Wallis) to determine statistical significance. Results: A total of 156 (78%) patients had symptoms suggestive of sleep disturbance and 163 (81.5%) patients were prescribed a sedative for sleep disturbance. Most patients were prescribed lorazepam (52 [26%]), followed by haloperidol (47 [23.5%]), and zopiclone (33 [16.5%]). Benzodiazepine and zopiclone prescribing decreased over time, while antipsychotic prescribing remained stable. When analyzed according to the most likely cause of the sleep disturbance, patients with insomnia had a higher Palliative Performance Score (P < .035) and were more likely to have a previous medical history of insomnia (P < .0003) than those with delirium. Both insomnia and delirium were quickly diagnosed but patients with unclear sleep disturbances took longer to recognize and treat. Conclusion: These results suggest that sleep disturbances are common at the end of life and can be challenging to categorize. Using specific criteria may be helpful in differentiating insomnia versus delirium and ultimately lead to more consistent approaches to management.

Benzodiazepine and z-drug prescribing in critical care survivors and the risk of rehospitalisation or death due to falls/trauma and due to any cause: a retrospective matched cohort study using the UK Clinical Practice Research Datalink.

Benzodiazepines and z-drugs are often prescribed to critical care survivors due to high prevalence of mental health problems and insomnia. However, their safety has not been studied in this population. Retrospective cohort study of 28,678 adult critical care survivors hospitalised in 2010 and 2018: 4844 prescribed benzodiazepines or z-drugs, matched to 23,834 unexposed survivors using UK Clinical Practice Research Datalink linked datasets. Multivariable stratified Cox regression was used to estimate the adjusted hazards ratio (adjHR) with 95% confidence intervals (CI) of community benzodiazepine/z-drug prescribing and falls/trauma-related events, as well as all-cause 30-day rehospitalisation or death. We performed subgroup analyses on patients without pre-critical care admission prescription of benzodiazepines/z-drugs ('treatment-naïve'), and sensitivity analyses excluding patients receiving palliative care after discharge. Prescription of benzodiazepines or z-drugs showed no conclusive evidence of increased risk of falls/trauma-related events in the whole cohort (adjHR 1.27; 95%CI 0.76-2.14) or in treatment-naïve individuals (adjHR 1.79; 95%CI 0.61-5.26), because estimates lacked precision due to low event rates. For all-cause rehospitalisation or death, benzodiazepines/z-drugs were associated with increased risk (whole cohort adjHR 1.24, 95%CI 1.14-1.36; treatment-naïve adjHR 1.66, 95%CI 1.49-1.86). However, after excluding patients treated for palliative care, the association persisted only in treatment-naïve individuals (whole cohort adjHR 1.08, 95%CI 0.98-1.19; treatment-naïve adjHR 1.42, 95%CI1.25-1.62). Community benzodiazepine and z-drug prescribing was associated with increased risk of all-cause, but not falls/trauma-related, rehospitalisations and deaths in critical care survivors who had not been prescribed these before hospitalisation. Clinicians should balance the possible benefits with the likely harms of prescribing these drugs in this potentially vulnerable patient group.

Effects of Protocol-driven Care by Internists on Adherence to Clinical Practice Guidelines for Hip Fracture Surgery Patients: An Interrupted Time Series Study Using a Nationwide Inpatient Database

Background Patients with hip fractures tend to have a poor prognosis. Although guideline-compliant practices are known to improve patient outcomes, there is a lack of evidence regarding the use of intervention to improve guideline adherence in hip fracture patients. The objective of our study was to evaluate guideline adherence by internists providing care to patients with hip fractures, using a protocol developed based on various guidelines. Method Protocol-driven care for hip fracture patients by internists began in April 2018 at our hospital. After its initiation, orthopedic surgeons performed the surgery, and the internists provided all other medical care. A controlled interrupted time-series analysis was used to evaluate the effects of protocol-driven care on guideline adherence to compare our hospital with other hospitals, using data extracted from a nationwide Japanese inpatient database covering the period April 2014 to March 2023. Results A total of 221,620 inpatients from 373 hospitals were included in the study. The initiation of protocol-driven care was associated with the guideline-recommended prescriptions: osteoporosis medication (Incidence rate ratio (IRR): 8.09; 95% CI 4.02-17.74), acetaminophen (IRR: 2.11; 95% CI 1.55-2.90), non-steroidal anti-inflammatory drugs (IRR: 0.16; 95% CI 0.11-0.24), and opioids (IRR: 5.96; 95% CI 3.14-12.15). However, there was no effect on the proportion of benzodiazepine prescriptions, surgery within 48 hours, deep venous thrombosis prophylaxis, or other perioperative outcomes, including medical fees. Conclusions The initiation of protocol-driven care by internists resulted in improved adherence to osteoporosis medication prescriptions and postoperative analgesic use compared with orthopedic care. This approach can be used as an effective method of care for elderly patients undergoing surgery.

Self-Harm as a Contributor to the Opioid Epidemic: Data From the Toxicology Investigators Consortium Registry.

Although considerable focus has been placed on understanding the causes of opioid drug overdoses, the intentions for such overdoses are not well characterized. We investigated the motivations behind nonfatal opioid exposures resulting in serious adverse health outcomes. We analyzed prospectively collected data on nonfatal opioid overdoses in the multicenter Toxicology Investigators Consortium (ToxIC) Core Registry between 2014 and 2021. Included patients were age ≥11 years with serious toxicity after use of pharmaceutical and/or nonpharmaceutical opioids for whom the reasons for opioid exposure were determined. Pharmaceutical opioids were defined as United States Food and Drug Administration-approved medications. All other opioids were classified as nonpharmaceuticals. The 5250 cases meeting the criteria were 56.6% male with a median age of 36 years (IQR, 26-50). There were 2960 (56.4%) opioid misuse cases and 1456 (27.7%) self-harm attempts. Within the self-harm group, 1242 (85.3%) were suicidal, and 1187 (95.6%) of these used pharmaceutical opioids in their suicide attempt. Only 94 (4.2%) patients using nonpharmaceutical opioids did so in a suicide attempt. Pharmaceutical opioid suicide attempts as a percent of all registry cases peaked between 2015 and 2017 and fell dramatically thereafter (P = 0.005). For comparison, benzodiazepine overdoses similarly decreased (P = 0.003), whereas non-opioid analgesic or antidepressant overdoses increased. A majority of serious opioid overdoses were sequelae of opioid misuse, but over a quarter were intentional self-harm attempts, primarily involving pharmaceutical opioids. Decreased prescribing of opioids and benzodiazepines after 2016-2017 may have resulted in decreased pharmaceutical opioid and benzodiazepine misuse and self-harm attempts. Similar trends were not seen for nonpharmaceutical opioids.

The Association Between Delirium Upon Admission to a Rehabilitation Hospital and Motor Rehabilitation Outcomes Among Hip Fracture Surgery Patients: A Historical Cohort Study.

Background: Delirium is a common neuropsychiatric syndrome characterized by the acute and fluctuating impairment of cognition, attention, and consciousness, which is prevalent in older adults following surgical procedures. Despite the recognized impact of delirium on recovery, its specific effects on motor rehabilitation outcomes in the geriatric population remain underexplored. This historical cohort study aimed to evaluate the association between the presence of delirium upon admission to a rehabilitation hospital and the motor functional gain at discharge among older patients following hip fracture surgery. Methods: The collected data included socio-demographic characteristics, comorbidities, medications, Mini-Mental State Examination (MMSE) scores, and the Functional Independence Measure (FIM). Motor rehabilitation outcomes were assessed using Motor Absolute Functional Gain (mAFG), the Montebello Rehabilitation Factor Score (mMRFS), and Rehabilitation Efficiency (mRE). Results: Of the 143 hip fracture patients admitted for rehabilitation, 38 (26.6%) were diagnosed with delirium. Patients with delirium had lower MMSE scores (18.1 ± 5.8 vs. 22.4 ± 6.0, p < 0.001), higher benzodiazepine prescription rates (50.0% vs. 14.3%, p < 0.001), and longer lengths of stay in acute care and rehabilitation (42.7 ± 10.4 vs. 37.3 ± 11.2 days, p = 0.01). Despite significant improvements in the FIM scores for both groups (p < 0.001), patients with delirium had lower mAFG (11.87 ± 7.26 vs. 15.91 ± 8.73, p = 0.01), mMRFS (0.22 ± 0.14 vs. 0.31 ± 0.15, p = 0.001), and mRE (0.28 ± 0.17 vs. 0.44 ± 0.25, p < 0.001). However, the multivariate regression models showed no association between delirium and functional improvement after adjusting for confounders. Conclusions: While both patients with and without delirium showed improvement in their motor functions by the time they were discharged from a rehabilitation hospital, patients with delirium showed lower absolute and relative improvements. Tailored programs addressing the special needs of patients with delirium after hip fracture surgery may enhance outcomes for this vulnerable population. A specialized, multidisciplinary approach tailored to the patient's cognitive status and overall condition is key to maximizing the recovery of older hip fracture patients with delirium.

Naloxone coprescribing best practice advisory for patients at high risk for opioid-related adverse events.

To implement an electronic health record best practice advisory (BPA) to promote coprescribing of naloxone to patients at high risk of serious opioid-related adverse events (ORADEs). This pre-post quasi-experimental study evaluated 9 months of opioid and naloxone prescription data before and after BPA implementation. The Froedtert & the Medical College of Wisconsin enterprise is comprised of 45 ambulatory clinics and 10 hospitals, including the only adult Level 1 trauma center in eastern Wisconsin. Patients who received opioid prescriptions in the preimplementation time period (n = 106,615 prescriptions) and post-implementation time period (n = 107,352 prescriptions) were included. BPA activation criteria included entry of a prescription with a morphine equivalent daily dose of 50 or greater with at least a 5-day supply, concomitant opioid and benzodiazepine prescription, or opioid prescription entry for a patient with a documented history of opioid overdose. The BPA defaulted to coprescribe naloxone, while also providing suppression options. The primary endpoint was the change in naloxone prescription rate for patients on chronic opioid therapy (COT) with a morphine milligram equivalent daily dose (MEDD) per day of 50 or greater. The naloxone coprescription rate for COT patients with a MEDD of 50 or greater increased from 12.2 percent (95 percent confidence interval [CI] 10.4-14.4) to 34.79 percent (95 percent CI 31.8-38.2) after the BPA was implemented (odds ratio 2.85, 95 percent CI 2.37-3.42, p-value < 0.001). Use of BPA increased the rate of naloxone coprescribing for patients at risk of serious ORADE.

EPH32 Trends in Benzodiazepine and Z-Drug Prescribing and Long-Term Use in Hong Kong: A Descriptive Cross-Sectional Study

EPH32 Trends in Benzodiazepine and Z-Drug Prescribing and Long-Term Use in Hong Kong: A Descriptive Cross-Sectional Study

Does Physicians' Clinical Competence, Communication Ability, or Cultural Background Influence Potentially Inappropriate Prescribing of Benzodiazepines and Z-Drugs Among Older Adults With Insomnia?

The objective of this study is to estimate the association between physician's age, sex, clinical and communication competencies, and cultural background on benzodiazepines and Z-drugs (BDZ) prescribing to older adults with insomnia. A cohort of international medical graduates (IMGs) who completed their pre-residency licensure exam in 1998-2004 were linked to all U.S. Medicare patients they provided care to in 2014-2015. Their care records in Parts A, B, and D from all physicians were extracted. The first outpatient visit for insomnia to a study IMG was identified for each patient in that period. The outcome was incident BDZ prescribing by the study physician following the visit. Main exposures were physician age, sex, citizenship at birth, and clinical and communication competency as measured on the licensure exam. The association between physician characteristics and BDZ prescribing, adjusting for physician and patient covariates, was estimated using generalized estimating equations multivariable logistic regression. We analyzed 28 018 patients seen by 4069 unique physicians. IMGs born in all other regions of the world were less likely to prescribe BDZs compared to U.S.-born IMGs, with physicians from the United Kingdom being least likely (OR 0.54 [95%CI 0.34-0.85]). Neither physician's clinical competency nor communication ability were associated with BDZ prescribing (OR per 10% increase, respectively: 0.95 [95%CI 0.88-1.02] and 0.98 [95%CI 0.93-1.04]). Older physicians remain more likely to prescribe BDZ (OR per 5-year increase 1.04 [95%CI 1.00-1.08]). The associations between cultural background and physician's age on BDZ prescribing highlight the potential targets for remedial solutions to reduce the use of potentially inappropriate medications.

Patient Characteristics and Practice Variation Associated With New Community Prescription of Benzodiazepine and z-Drug Hypnotics After Critical Illness: A Retrospective Cohort Study Using the UK ClinicalPracticeResearch Datalink.

Survivors of critical illness are often affected by new or worsened mental health conditions and sleep disorders. We examined the incidence, practice variation and factors associated with new benzodiazepine and z-drug community prescriptions among critical illness survivors. A retrospective cohort study using the UK Clinical Practice Research Datalink data included 52 846 adult critical care survivors hospitalised in 2010 and 2018 who were not prescribed benzodiazepines or z-drugs before hospitalisation. We performed multilevel multivariable logistic regression to assess patient factors associated with new (any prescription within 90 days) and with new-and-persistent (2+ prescriptions within 180 days) benzodiazepine or z-drug prescribing, and to evaluate variation by primary care practice. 5.2% (2769/52846) of treatment-naïve survivors (95% CI 5.1-5.4) were prescribed a benzodiazepine or z-drug, and 2.5% (1311/52846) had new-and-persistent prescribing. A history of insomnia (adjusted OR 1.96; 95% CI 1.74-2.21), anxiety or depression (adjusted OR 1.40; 95% CI 1.28-1.53) and recent prescription opioid use (adjusted OR 1.47; 95% CI 1.34-1.61) were associated with new community prescription. Sex was not associated with new prescriptions and older patients were less likely to receive a prescription. 2.6% of the variation in new prescribing and 4.1% of the variation in new-and-persistent prescribing were attributable to the prescribing practice. One in twenty critical illness survivors receive a new community benzodiazepine or z-drug prescription. Further research is needed to understand where in the patient care pathway initiation occurs and the risk of adverse events in survivors of recent critical illness.

Four-year evaluation of drug-impaired driving drug concentrations.

Drug-impaired driving is a significant public health and safety concern in the USA. To help assess current patterns of drug use in drivers, we evaluated 4 years of drug positivity in a large cohort of suspected impaired drivers. Samples collected between January 2017 and December 2020 were tested via a method compliant with the National Safety Council's Alcohol, Drugs, and Impairment Division's Tier I scope of recommended drugs. In 2017, NMS Labs received 17 346 driving under the influence of drugs cases, 17 471 in 2018, 19 050 in 2019, and 16 539 in 2020. The most common drug class detected was cannabinoids in ∼50% of the cases each year. The most common drugs detected over the 4 years were delta-9 tetrahydrocannabinol (delta-9 THC), ethanol, amphetamine/methamphetamine, fentanyl, and alprazolam. Delta-9 THC increased in positivity over the study, having been identified in 45% of cases in 2017, 46% in 2018, 46% in 2019, and 49% in 2020. Ethanol was found in 59% of cases in 2017, 59% in 2018, 61% in 2019, and 53% in 2020. Delta-9 THC and ethanol were the most common drug combination, found together in ∼19% of the cases every year of the study. Statistically significant increases in the average concentration of the following drugs were observed: fentanyl (5.7 ng/mL in 2017 to 9.6 ng/mL in 2020), methamphetamine (301 ng/mL in 2017 to 381 ng/mL in 2020), and delta-9-THC (6.4 ng/mL in 2017 to 7.3 ng/mL in 2020). Other findings included increases in the maximum reported concentrations between 2017 and 2020 for amphetamine (1400 to 2700 ng/mL), methamphetamine (5550 to 13 000 ng/mL), and fentanyl (56 to 310 ng/mL). Statistically significant concentration decreases were noted for several central nervous system depressants, notably prescription benzodiazepines, and several prescription narcotic analgesics.

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&lt;.001), the rate of ischemic stroke was 16% and 23.4%(p=.008), the rate of MI was 11.9% and 22.5%(p&lt;.001), and the rate of hospitalization was 51.8% and 59.5%(p&lt;.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&lt;.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.

Dispensing of zolpidem and benzodiazepines in Brazilian private pharmacies: a retrospective cohort study from 2014 to 2021.

The study aimed to evaluate Zolpidem and Benzodiazepines prescription and dispensing data in private pharmacies in Brazil from 2014 to 2021. Methods: This retrospective cohort study was carried out with retrospective open data from the Brazilian Federal Government from January 2014 to August 2021 containing medicines registered in the National Controlled Products Management System (SNGPC). Between January 2014 and August 2021, a total of 32,441,392 sales of thirteen drugs from the z-drug and benzodiazepine classes used to treat sleep disorders were recorded in Brazil. Throughout the entire period, clonazepam emerged as the most popular drug, accounting for 29.8% of total sales. Alprazolam followed in second place with 20.6% of sales, while zolpidem came in third with 14.4%. The normal-release form of zolpidem was consistently the highest-selling variant during the evaluation period. However, the fast-acting-release form exhibited the most significant growth, indicated by a noticeable upward trend in sales since 2020. In contrast, the extended-release form of zolpidem remained stable over the years. The increased sales of zolpidem in Brazilian private pharmacies raise concerns about potential misuse and dependence on this drug mainly for the treatment of insomnia. The epidemic of sleeping pills arises in a scenario of expectancy of short-term amelioration of symptoms, with no correspondence in best clinical practice. Education and counseling for both healthcare professionals and the general population are essential to address this growing health concern and ensure the safe and appropriate use of medications for sleep disorders.

Prescription of benzodiazepines and antidepressants among Sami and non-Sami — How childhood violence shapes prescription patterns: the SAMINOR 2 questionnaire survey and the Norwegian prescription database

BackgroundMedication for mental health problems represents a significant proportion of overall medication use and the prescription of psychotropic medicine has increased in many western countries over the last decades. Childhood violence (CV) is strongly associated with mental health problems, which in turn may increase the likelihood of being prescribed psychotropic medication. However, the association between CV and prescription of benzodiazepines (BDZ) and antidepressants is rarely described, and no such study has been performed among the Indigenous Sami people.MethodsData from the SAMINOR 2 Questionnaire Survey (2012) was linked to the Norwegian Prescription Database. Information on filled prescriptions for BDZ and antidepressants in 2004–2019 was collected for 11,296 persons (55.8% women, 22.6% Sami). Gender-stratified chi-square tests and two-sample t-tests were used to test for differences between groups. Logistic regression was applied to investigate the association between CV and filled prescriptions for BDZ and antidepressants.ResultsDuring the 16-year study period, 16.7% of all women filled at least one prescription for BDZ. The figures were significantly lower among Sami women (14.1%) compared to non-Sami women (17.4%) (p = .003). Among all women, 23.6% filled at least one prescription for antidepressants, with no difference between ethnic groups. Filled prescriptions among men were 10.0% and 14.2%, respectively, with no difference between ethnic groups. During each year, and in total, a significantly higher proportion of women exposed to CV received at least one prescription for BDZ and antidepressants, respectively, compared to women not exposed to CV, with no differences between ethnic groups. Among men, the pattern was similar.ConclusionA lower proportion of Sami women filled prescriptions for BDZ than non-Sami women. Those who reported exposure to CV filled prescriptions for BDZ and antidepressants more often than those who did not report CV. There were no overall differences between Sami and non-Sami; the dispensing rates of antidepressants and BDZ were similar for Sami and non-Sami, and the effects of CV on the dispensing of antidepressants and BDZ were also similar. This study highlights the importance of preventing CV, and of identifying a history of CV when treating adults with mental health problems.

The association between benzodiazepine prescriptions and the risk of laxative use in schizophrenia treatment.

Constipation is one of the most common adverse effects in schizophrenia treatment, and it can sometimes cause severe gastrointestinal disease. However, the results of association studies between constipation and psychotropic medications in patients with schizophrenia are inconsistent. Therefore, we investigated the characteristics of psychotropic and laxative prescriptions at discharge in patients with schizophrenia to clarify the association between psychotropics and constipation. We analyzed the data of 139 patients with schizophrenia with or without laxative prescriptions at discharge from eight institutions in 2020. Sixty-two patients were prescribed laxatives at discharge. The prescription of benzodiazepines in the laxative use group (66.1%) was significantly higher than that in the non-laxative use group (39.0%) (p = 1.4 × 10-3), and the mean number of benzodiazepines in the laxative use group (1.2 ± 1.1/day) was significantly higher than that in the non-laxative use group (0.7 ± 0.9/day) (p = 2.6 × 10-3). Multivariate logistic regression analyses revealed that benzodiazepine prescriptions were significantly associated with laxative usage (odds ratio, 3.059; 95% confidence interval, 1.523-6.144; p = 2.0 × 10-3). Benzodiazepines may be associated with constipation in patients with schizophrenia. Therefore, clinicians should be cautious when prescribing benzodiazepines for the treatment of schizophrenia.