Co-prescription Of Benzodiazepines Research Articles

Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy: a population-based cohort study

ObjectiveTo investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone.DesignPopulation-based cohort study.SettingScotland, UK.ParticipantsParticipants were people prescribed ORT...

Time trends and patterns in opioid prescription use following orthopaedic surgery in Ontario, Canada, from 2004/2005 to 2017/2018: a population-based study

ObjectivesIncreased use of opioids and their associated harms have raised concerns around prescription opioid use for pain management following surgery. We examined trends and patterns of opioid prescribing following elective...

Opioid and Benzodiazepine Co-Prescribing Trends from the Emergency Department from 2012 to 2019: A National Analysis

BackgroundIn 2016, the U.S. Food and Drug Administration (FDA) issued its strongest safety warning (“Black Box Warning”) for concomitant use of prescription opioids and benzodiazepines due to overdose deaths. ObjectiveOur objective was to look at trends of opioid and benzodiazepine co-prescribing in the emergency department (ED) using national data, because recent data are sparse. MethodsThis is a retrospective review of data collected by the National Hospital Ambulatory Medical Care Survey between 2012 and 2019. Our primary outcome was to determine whether there was a trend in ED visits when opioids and benzodiazepines were co-prescribed at discharge. We also compared the rate of visits when co-prescribing occurred before (2012–2015) and after (2017–2019) the 2016 FDA warning. We identified commonly co-prescribed benzodiazepines and opioids, and the rate of naloxone co-prescribing. We used descriptive statistics and bivariate tests to describe data. ResultsBetween 2012 and 2019, there were 4,489,613 ED visits (0.41% of ED visits) when benzodiazepines and opioids were co-prescribed. There was no trend in the rate of co-prescribing overall, but a decrease in visits after the 2016 FDA Black Box Warning (2012–2015: mean 0.49%; 2017–2019: mean 0.29%; p < 0.0001). There were 7980 ED visits (0.18%) when naloxone was co-prescribed for these visits within this time frame and an increase over time (p < 0.001). ConclusionsOur study found that between 2012 and 2019, there was no overall reduction in co-prescribing of opioids and benzodiazepines across EDs nationwide, but a decrease after the 2016 Black Box Warning.

E051 A systematic review of audit and feedback tools to reduce opioid prescribing for chronic non-cancer pain

Abstract Background/Aims Opioid prescribing has increased considerably over the 15 years for chronic non-cancer pain in the UK, including for musculoskeletal conditions. Whilst there are national and international guidelines to reduce inappropriate opioid prescribing, these are not always adhered to in practice. Audit and feedback is a common intervention for supporting clinical behaviour change. Little is known if such tools have been used to support safer opioid prescribing to date. This systematic review aimed to describe audit and feedback tools that were designed, implemented and led to changes in opioid prescribing practices. Methods A systematic review of the literature was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework (PRISMA). Both Embase and MEDLINE were searched to identify studies that included audit and feedback tools in patients prescribed opioids with chronic non-cancer pain until the 31st of May 2021. Results Of the 539 studies imported, following removal of duplicates, 497 studies were screened. Following title and abstract review 6 full-text studies were assessed for eligibility. A total of three studies were deemed to meet inclusion criteria. Approaches found included: The Controlled Medication Advisory Board (CMAB), Systems Consultation and the Opioid Safety Initiative (OSI). CMAB involved the use of a dashboard to provide feedback to clinicians on referred patients. As a result the opioid prescribing rate per 100 patient visits decreased by 31% and the rate of co-prescription of benzodiazepines and opioids decreased by 56%. Systems Consultation involved the use of audit and feedback, academic detailing and external facilitation to reduce opioid prescribing. Systems consultation resulted in a statistically significant reduction in the morphine equivalent daily doses. The OSI used automatic electronic medical records auditing to enable clinic leaders to identify physician prescribing patterns via a dashboard. OSI enabled a 9.9% reduction in opioid prescriptions from 571,476 to 514,883. Conclusion Computerised audit and feedback tools may be effective interventions to support opioid stewardship initiative and promote safer opioid prescribing. Such approaches being used internationally could pave the way for similar initiatives in the UK and future research evaluating their impact on patient safety. Disclosure J. Feldman: None. M. Jani: Grants/research support; National Institute for Health and Care Research Advanced Fellowship (NIHR301413).

Association of Primary Care Visit Length With Potentially Inappropriate Prescribing

Time is a valuable resource in primary care, and physicians and patients consistently raise concerns about inadequate time during visits. However, there is little evidence on whether shorter visits translate into lower-quality care. To investigate variations in primary care visit length and quantify the association between visit length and potentially inappropriate prescribing decisions by primary care physicians. This cross-sectional study used data from electronic health record systems in primary care offices across the US to analyze adult primary care visits occurring in calendar year 2017. Analysis was conducted from March 2022 through January 2023. Regression analyses quantified the association between patient visit characteristics and visit length (measured using time stamp data) and the association between visit length and potentially inappropriate prescribing decisions, including inappropriate antibiotic prescriptions for upper respiratory tract infections, coprescribing of opioids and benzodiazepines for painful conditions, and prescriptions that were potentially inappropriate for older adults (based on the Beers criteria). All rates were estimated using physician fixed effects and were adjusted for patient and visit characteristics. This study included 8 119 161 primary care visits by 4 360 445 patients (56.6% women) with 8091 primary care physicians; 7.7% of patients were Hispanic, 10.4% were non-Hispanic Black, 68.2% were non-Hispanic White, 5.5% were other race and ethnicity, and 8.3% had missing race and ethnicity. Longer visits were more complex (ie, more diagnoses recorded and/or more chronic conditions coded). After controlling for scheduled visit duration and measures of visit complexity, younger, publicly insured, Hispanic, and non-Hispanic Black patients had shorter visits. For each additional minute of visit length, the likelihood that a visit resulted in an inappropriate antibiotic prescription changed by -0.11 percentage points (95% CI, -0.14 to -0.09 percentage points) and the likelihood of opioid and benzodiazepine coprescribing changed by -0.01 percentage points (95% CI, -0.01 to -0.009 percentage points). Visit length had a positive association with potentially inappropriate prescribing among older adults (0.004 percentage points; 95% CI, 0.003-0.006 percentage points). In this cross-sectional study, shorter visit length was associated with a higher likelihood of inappropriate antibiotic prescribing for patients with upper respiratory tract infections and coprescribing of opioids and benzodiazepines for patients with painful conditions. These findings suggest opportunities for additional research and operational improvements to visit scheduling and quality of prescribing decisions in primary care.

Gabapentin, Concomitant Prescription of Opioids, and Benzodiazepines among Kidney Transplant Recipients.

Gabapentinoids, commonly used for treating neuropathic pain, may be misused and coprescribed with opioid and benzodiazepine, increasing the risk of mortality and dependency among kidney transplant recipients. We identified adult kidney transplant recipients who enrolled in Medicare Part D in 2006-2017 using the United States Renal Data System/Medicare claims database. We characterized recipients' post-transplant concomitant prescription of gabapentinoids, opioids, and benzodiazepine stratified by transplant year and recipient factors (age, sex, race, and diabetes). We investigated whether concomitant prescriptions were associated with postkidney transplant mortality using Cox regression. Models incorporated inverse probability weighting to adjust for confounders. Among 63,359 eligible recipients, 13% of recipients filled at least one gabapentinoid prescription within 1 year after kidney transplant. The prevalence of gabapentinoid prescriptions increased by 70% over the study period (16% in 2017 versus 10% in 2006). Compared with nonusers, gabapentinoids users were more likely to have diabetes (55% versus 37%) and obesity (46% versus 34%). Of the 8509 recipients with gabapentinoid prescriptions, 45% were coprescribed opioids, 7% were coprescribed benzodiazepines, and 3% were coprescribed both opioids and benzodiazepines. Compared with no study prescriptions, gabapentinoid monotherapy (adjusted hazard ratio [aHR]=1.25; 95% confidence interval [CI], 1.16 to 1.32) and combination therapy (gabapentinoids and opioids [aHR=1.49; 95% CI, 1.39 to 1.60], gabapentinoids and benzodiazepines [aHR=1.46; 95% CI, 1.03 to 2.08], and coprescribing all three [aHR=1.88; 95% CI, 1.18 to 2.98]) were all associated with a higher risk of postkidney transplant mortality. Gabapentinoid coprescription with both benzodiazepines and opioids among kidney transplant recipients increased over time. Kidney transplant recipients prescribed gabapentinoids had a higher risk of post-transplant mortality, and the risk was higher with opioids or benzodiazepine coprescription.

Co-prescribing of opioids and benzodiazepines/Z-drugs associated with all-cause mortality-A population-based longitudinal study in primary care with weak opioids most commonly prescribed.

Introduction: The risk of mortality associated with the co-prescribing of benzodiazepines and opioids has been explored in a number of papers mainly focusing on strong opioids. The mortality risk associated with the use of weak opioids has not been dealt with to a similar extent. Objective: To assess the mortality risk in primary care patients with consistent 3-year co-prescribing of benzodiazepine/Z-drugs (benzodiazepine receptor modulators) and mainly weak opioids (codeine, tramadol). Methods: Of 221,804 patients contacting the primary healthcare centres, 124,436 were selected for further analysis, 88,832 participants fulfilled the inclusion criteria, aged 10–69 years and were divided into four groups with neither any use of benzodiazepines/Z-drugs nor opioids as Group 1, 3 years’ use of opioids and no/minimal benzodiazepines/Z-drugs as Group 2, with benzodiazepines/Z-drugs and no/minimal opioids as Group 3, and finally both benzodiazepines/Z-drugs and opioids as Group 4. Hazard ratios were calculated with the no-drug group as a reference, using Cox proportional hazards regression model adjusted for age, sex, number of chronic conditions and cancer patients excluded (n = 87,314). Results: Hazard ratios for mortality increased both in Group 3 where it was 2.66 (95% CI 2.25–3.09) and in Group 4 where it was 5.12 (95% CI 4.25–6.17), with increased dose and higher number of chronic conditions. In Group 4 an opioid dose-dependent increase in mortality among persons using >1000 DDDs benzodiazepines/Z-drugs was observed when those on less than ≤300 DDDs of opioids with HR 4.94 (95% CI 3.54–6.88) were compared to those on >300 DDDs with HR 7.61/95% CI 6.08–9.55). This increase in mortality was not observed among patients on <1000 DDDs of benzodiazepines/Z-drugs. Conclusion: The study supports evidence suggesting that mortality increases in a dose-dependent manner in patients co-prescribed benzodiazepines/Z-drugs and weak opioids (codeine, tramadol). An association between the number of chronic conditions and a rise in mortality was found. Long-term use of these drugs should preferably be avoided. Non-pharmacological therapy should be seriously considered instead of long-term use of benzodiazepines/Z-drugs, and deprescribing implemented for chronic users of these drugs when possible.

Cross-sectional study of the prevalence of prescription opioids misuse in French patients with chronic non-cancer pain: An update with the French version of the POMI scale.

Public health issues related to chronic pain management and the risks of opioid misuse and abuse remain a challenge for practitioners. Data on the prevalence of disorders related to the use of prescribed opioids in patients suffering from chronic pain remains rather patchy, in particular because of the absence of a gold standard for their clinical assessment. We estimated the prevalence of prescription opioid misuse (POM), using a specific and validated opioid misuse scale (POMI-5F scale), in adults with chronic non-cancer pain. Nine-hundred-fifty-one (951) patients with opioids prescription and followed-up in pain clinics and addictology centers for chronic non-cancer pain (CNCP) completed the survey interview. The results suggest that 44.4% of participants have POM, accompanied by overuse (42.5%), use of opioids for effects other than analgesia (30.9%), withdrawal syndrome (65.7%), and craving (6.9%). The motivations cited for POM, apart from pain relief, were to calm down, relax and improve mood. POM was shown to be related to male sex (OR 1.52), young age (OR 2.21) and the presence of nociplastic pain (OR 1.62) of severe intensity (OR 2.31), codeine use (OR 1.72) and co-prescription of benzodiazepines (OR 1.59). Finally, despite the presence of three subgroups of misusers, no factor was associated with the intensity of misuse, reinforcing the view that distinguishing between strong and weak opioids is not appropriate in the context of use disorder. Almost half of patients with CNCP misuse their prescribed opioid. Practitioners should be attentive of profiles of patients at risk of POM, such as young, male patients suffering from severe nociplastic pain, receiving prescription for codeine and a co-prescription for benzodiazepine. We encourage French-speaking practitioners to use the POMI-5F scale to assess the presence of POM in their patients receiving opioid-based therapy. Clinical Trial Registration clinicaltrials.gov, identifier NCT03195374

Frailty Risks of Prescription Analgesics and Sedatives across Frailty Models: the Health and Retirement Study.

Limited evidence for incident frailty risks associated with prescription analgesics and sedatives in older (≥65 years) community-living adults prompted a more comprehensive investigation. We used data from older Health and Retirement Study respondents and three frailty models (frailty index, functional domain, frailty phenotype with 8803, 10,470, and 6850 non-frail individuals, respectively) and estimated sub-hazard ratios of regular prescription drug use (co-use, analgesic use, and sedative use), by frailty model. We addressed confounding with covariate adjustment and propensity score matching approaches. The baseline prevalence of analgesic and sedative co-use, analgesic use, and sedative use among non-frail respondents was 1.8%, 12.8%, and 4.7% for the frailty index model, 4.2%, 16.2%, and 5.3% for the functional domain model, and 4.3%, 15.4%, and 6.1% for the frailty phenotype model, respectively. Cumulative frailty incidence over 10 years was 39.3%, 36.1%, and 14.2% for frailty index, functional domain, and frailty phenotype models, respectively; covariate-adjusted sub-hazard ratio estimates were 2.00 (1.63-2.45), 1.83 (1.57-2.13), and 1.68 (1.21-2.33) for co-use; 1.72 (1.56-1.89), 1.38 (1.27-1.51), and 1.51 (1.27-1.79) for analgesic use; and 1.46 (1.24-1.72), 1.25 (1.07-1.46), and 1.31 (0.97-1.76) for sedative use. Frailty risk ranking (co-use > analgesic use > sedative use) persisted across all model sensitivity analyses. Consistently significant frailty risk estimates of regular prescription analgesic and sedative co-use and of prescription analgesic use support existing clinical, public health, and regulatory guidance on opioid and benzodiazepine co-prescription, on opioid prescription, and on NSAID prescription. Frailty phenotype measurement administration limited power to detect significant frailty risks. Research into specific pharmaceutical exposures and comparison of results across cohorts will be required to contribute to the deprescribing evidence base.

Naloxone prescribing practices in the Military Health System before and after policy implementation.

Despite public health campaigns, policies, and educational programs, naloxone prescription rates among people receiving opioids remains low. In June 2018, the U.S. Military Health System (MHS) released 2 policies to improve naloxone prescribing. The objective of this study was to examine whether the policies resulted in increased naloxone coprescription rates for patients who met the criteria for 1 or more risk indicators (eg, long-term opioid therapy, benzodiazepine coprescription, morphine equivalent daily dose ≥50 mg, and elevated overdose risk score) at the time of opioid dispense. Prescription and risk indicator data from January 2017 to February 2021 were extracted from the MHS Data Repository. Naloxone coprescription rates from January 2017 to September 2018 were used to forecast prescribing rates from October 2018 to February 2021 overall and across risk indicators. Forecasted rates were compared with actual rates using Bayesian time series analyses. The probability of receiving a naloxone coprescription was higher for patients whose opioid prescriber and pharmacy were both within military treatment facilities vs both within the purchased-care network. Bayesian time series results indicated that the number of patients who met the criteria for any risk indicator decreased throughout the study period. Naloxone prescribing rates increased across the study period from <1% to 20% and did not significantly differ from the forecasted rates across any and each risk indicator (adjusted P values all >0.05). Future analyses are needed to better understand naloxone prescribing practices and the impact of improvements to electronic health records, decision support tools, and policies.

The impact of CARA mandates on nurse practitioner controlled substance prescribing in Oregon: a cohort study

BackgroundIn 2017, the United States Comprehensive Addiction and Recovery Act (CARA) expanded authorization to prescribe buprenorphine for opioid use disorder (OUD) to nurse practitioners (NPs). Compared to physicians, NPs were required to complete 16 additional hours of training on controlled substance prescribing before a buprenorphine waiver application. As this differential additional education mandate was seen as a potential barrier, we evaluated the impact of this requirement on both NP waiver acquisition and prescribing of controlled substances, comparing NPs who obtained waivers to those who had not.MethodsThrough 2016–2018 Oregon Prescription Drug Monitoring Program and linked NP licensure data, we identified factors associated with waiver acquisition at baseline (2016) and evaluated changes in controlled substance prescribing before (2016) and after waiver acquisition (2018). Using chi-square and Mann-Whitney U testing, we calculated and described controlled substance prescribing types, rates, and patient level quantities including co-prescribing of benzodiazepines and opioids by NPs. Multivariable linear regression compared prescribing by waivered and non-waivered NPs for significant changes in non-buprenorphine controlled substance prescribing.ResultsWaivered NPs were more likely to have a psychiatric certification, have prior disciplinary action, and have generally higher levels of non-buprenorphine controlled substance prescribing than their non-waivered counterparts. While there was a significant increase in opioid prescriptions per patient among waivered NPs, following CARA implementation, co-prescribing of benzodiazepines and opioids significantly declined among waivered NPs relative to non-waivered NPs.ConclusionsAlthough educational requirements were rescinded in 2021 for most applicants, enhanced opioid prescribing training should be incorporated into professional educational offerings regardless of regulatory mandate. We recommended continued focus on education regarding avoidance of high risk prescribing such as co-prescribing of opioids and benzodiazepines. NPs who acquire waivers may take on higher risk patients already using opioids, and these findings may represent transitions in practice and patient setting.

Coprescribing of benzodiazepines with SSRIs continues to raise concern

Simultaneous initiation of benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) in young people with anxiety disorders declined from 2008 to 2016 but remains relatively common, a study examining a U.S. commercial insurance database reported. Coprescribing of benzodiazepines and SSRIs was not associated with longer duration in SSRI treatment.

Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study

ObjectiveExamine the association between the co-prescribing of opioids, benzodiazepines, gabapentinoids (pregabalin and gabapentin) and selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors (SSRI/SNRIs) in different combinations and the risk of...

Prescription fill patterns for benzodiazepine and opioid drugs during the COVID-19 pandemic in the United States

BackgroundCOVID-19 and resulting mitigation measures in the United States (US) brought about limited access to medical care that has been linked to increases in mental health problems, excessive substance use, and drug overdoses. The increase in co-prescription of benzodiazepines and opioids may indicate population-level changes in health behaviors that can be exacerbated by limited access, hence necessitating the tracking of these drugs during COVID-19. We evaluated the impact of the declaration of COVID-19 as a US national emergency on prescription patterns in 2020. MethodsPrescriptions of benzodiazepines and opioids were analyzed using data aggregated on a weekly basis across 38 states over the January 2019-December 2020 period. Data were from Bamboo Health Prescription Drug Monitoring Program and covered all individuals regardless of insurance status. Generalized additive models estimated the effects of the March 13, 2020 declaration on proportion of prescriptions to all controlled substances by comparing volumes before to after the week of March 13 in 2020 (range: January 27-May 24) and comparing this trend to its 2019 counterpart. ResultsWhen comparing the January 27-March 9 period to the March 16-May 24 period in 2020, there was a statistically significant 2.0% increase in the proportion of benzodiazepine dispensations to all controlled substances, and a significant 1.7% mean decrease in proportion of opioid dispensations to all controlled substances. A significant return approaching pre-declaration levels was observed only for opioids (beginning week of May 18, 2020). ConclusionsThe results suggest significant impacts of the COVID-19 pandemic on dispensations of benzodiazepines and opioids across the US. Continued monitoring of prescription trends and maintenance of adequate and accessible access to mental healthcare are important for understanding public health crises related to substance use.

Initiation of Long-Acting Opioids Following Hospital Discharge Among Medicare Beneficiaries.

Guidelines recommend against initiating long-acting opioids during acute hospitalization, owing to higher risk of overdose and morbidity compared to short-acting opioid initiation. We investigated the incidence of long-acting opioid initiation following hospitalization in a retrospective cohort of Medicare beneficiaries with an acute care hospitalization in 2016 who were ≥65 years old, did not have cancer or hospice care, and had not filled an opioid prescription within the preceding 90 days. Among 258,193 hospitalizations, 47,945 (18.6%) were associated with a claim for a new opioid prescription in the week after hospital discharge: 817 (0.3%) with both short- and long-acting opioids, 125 (0.1%) with long-acting opioids only, and 47,003 (18.2%) with short-acting opioids only. Most long-acting opioid claims occurred in surgical patients (770 out of 942; 81.7%). Compared with beneficiaries prescribed short-acting opioids only, beneficiaries prescribed long-acting opioids were younger, had a higher prevalence of diseases of the musculoskeletal system and connective tissue, and had more known risk factors for opioid-related adverse events, including anxiety disorders, opioid use disorder, prior long-term high-dose opioid use, and benzodiazepine co-prescription. These findings may help target quality-improvement initiatives.

System intervention in community pharmacy setting: Leading to better patient care through reducing harm associated with coprescribing benzodiazepines and opioids.

The opioid epidemic is frequently discussed including the staggering numbers involved with coprescribing opioids and benzodiazepines associated with death. Community pharmacists, with the help of a system intervention, have a unique opportunity to help reduce the coprescribing of benzodiazepines and opioids and reduce the associated risk of death. A single center retrospective chart review was conducted after a system intervention was placed, as a quality improvement project, from November 2019 to May 2020. Independent community pharmacy. Data included demographics, dosing of each medication pre- and post-intervention, and naloxone status. Main outcome(s) measures: The primary outcome evaluated was reduction in dose/discontinuation of these prescriptions. The secondary outcome evaluated was the number of naloxone prescriptions ordered per protocol and picked up. The primary outcome did not show statistical difference; however, the secondary outcomes showed statistical significance. In conclusion, community pharmacists, with the help of evolving technologies, can reduce harm associated with the coprescribing of benzodiazepines and opioids.

Trends in prescribing pattern of opioid and benzodiazepine substitutes among Medicare part D beneficiaries from 2013 to 2018: a retrospective study

ObjectiveOpioid and benzodiazepine co-prescribing is associated with a substantial increase in opioid overdose deaths. In this study, we examine the prescribing trends of substitutes of opioids and benzodiazepines alone or...

Mental Health and Benzodiazepine Use Among Patients on Chronic Opioid Therapy.

Higher daily doses of opioids as well as co-prescription of benzodiazepines have been associated with risk of overdose. The current study characterizes prescribing patterns in a family medicine practice with regard to patient mental health diagnoses, benzodiazepine prescriptions, morphine milligram equivalent opioid dose, and patient demographics. Patients on chronic opioid therapy were studied in 2018 and 2019. Mental health diagnoses, opioid dose, benzodiazepine prescriptions and demographic characteristics were extracted from the electronic health record. Data were compared between years and logistic regression was used to determine which patient characteristics were associated with likelihood of decreased opioid dose. A total of 387 patients were prescribed chronic opioid therapy in 2018, and 231 in 2019. In 2018, 49.9% of patients prescribed chronic opioids had mental health diagnoses. In 2019, this proportion rose to 92.2%. In 2019, 205 of the original 387 patients were still with the practice but were not prescribed chronic opioids. Among the factors studied, psychiatric diagnosis and higher opioid dose were associated with a significantly lower likelihood of tapering doses. As practices taper or de-prescribe opioids, or implement harm reduction methods such as de-prescribing benzodiazepines, it is important to understand patient characteristics and their relationship to success with tapering. This study adds to the evidence that odds of successfully tapering opioids may be significantly impacted by patients' mental health diagnosis and opioid dose.

Emergency Department Utilization Among People Living With HIV on Chronic Opioid Therapy.

Chronic pain among people with HIV (PWH) is a driving factor of emergency department (ED) utilization, and it is often treated with chronic opioid therapy (COT). We conducted a cross-sectional analysis of a prospective observational cohort of PWH on COT at 2 hospital-based clinics to determine whether COT-specific factors are associated with ED utilization among PWH. The primary outcome was an ED visit within 12 months after study enrollment. We used stepwise logistic regression including age, gender, opioid duration, hepatitis C, depression, prior ED visits, and Charlson comorbidity index. Of 153 study participants, n = 69 (45%) had an ED visit; 25% of ED visits were pain-related. High dose opioids, benzodiazepine co-prescribing, and lack of opioid treatment agreements were not associated with ED utilization, but prior ED visits (p = 0.002), depression (p = 0.001) and higher Charlson comorbidity score (p = 0.003) were associated with ED utilization. COT-specific factors were not associated with increased ED utilization among PWH.

Association Between Benzodiazepine Use With or Without Opioid Use and All-Cause Mortality in the United States, 1999-2015

Although overall rates of opioid use have been plateauing, coprescriptions of benzodiazepines and opioids have increased greatly in recent years. It is unknown whether this combination is an independent risk factor for all-cause mortality as opposed to being more frequently used by persons with a baseline elevated risk of death. To evaluate whether benzodiazepine use, with or without opioid use, is associated with increased all-cause mortality relative to the use of low-risk antidepressants. This retrospective cohort study used a large, nationally representative US data set (the National Health and Nutrition Examination Surveys [NHANES]) from 1999 to 2015. Eight cycles of NHANES data were used, spanning 37 610 person-years of follow-up time among 5212 individuals. Statistical analysis was performed from August 24, 2019, through May 23, 2020. The primary exposure variable was benzodiazepine and opioid coprescriptions. Individuals taking selective serotonin reuptake inhibitors (SSRIs) served as an active comparator reference group. All-cause mortality was obtained via linkage of NHANES to the National Death Index. Propensity scores were calculated from covariates associated with sociodemographic factors, comorbidities, and medication use for more than 1000 prescription types. Propensity score-weighted mortality hazards were calculated from Cox proportional hazards regression models. Of 5212 participants aged 20 years or older (1993 men [38.2%]; mean [SD] age, 54.8 [16.9] years) followed up for a median of 6.7 years (range, 0.2-16.8 years), 101 deaths (33.0 per 1000 person-years) occurred among those receiving cotreatment, 236 deaths (26.5 per 1000 person-years) occurred among those receiving only benzodiazepines, and 227 deaths (20.2 per 1000 person-years) occurred among SSRI recipients taking neither opioids nor benzodiazepines. After propensity score weighting, a significant increase in all-cause mortality was associated with benzodiazepine and opioid cotreatment (hazard ratio, 2.04 [95% CI, 1.65-2.52]) and benzodiazepines without opioids (hazard ratio, 1.60 [95% CI, 1.33-1.92]). Subgroup analyses revealed an increased risk of mortality for individuals receiving cotreatment who were 65 years or younger but not for those older than 65 years; similar findings were observed for those receiving benzodiazepines without opioids. This study found a significant increase in all-cause mortality associated with benzodiazepine use with or without opioid use in comparison with SSRI use. Benzodiazepine and opioid cotreatment, in particular, was associated with a 2-fold increase in all-cause mortality even after taking into account medical comorbidities and polypharmacy burden.