Association of Fatal Overdose Notification Letters With Prescription of Benzodiazepines: Secondary Analysis of a Randomized Clinical Trial.
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ABSTRACT:
SUBMITTER: Kelley MA
PROVIDER: S-EPMC9396468 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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Association of Fatal Overdose Notification Letters With Prescription of Benzodiazepines: Secondary Analysis of a Randomized Clinical Trial.
Kelley Marcella A MA Lev Roneet R Lucas Jonathan J Knight Tara T Stewart Emily E Menchine Michael M Doctor Jason N JN
JAMA internal medicine 20221001 10
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Project description:Objectives To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose.Design Retrospective analysis of claims data, 2001-13.Setting Administrative health claims database.Participants 315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid.Interventions Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug. Main outcome measures Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose.Results 9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P<0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P<0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P<0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16).Conclusions From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.
| S-EPMC5421443 | biostudies-literature
Project description:Background and aimsIn the US, benzodiazepine overdose deaths increased at an alarming rate in the past two decades. Benzodiazepines were also the most common drugs involved in prescription opioid overdose deaths. Benzodiazepine prescribing has been monitored by Prescription Drug Monitoring Programs (PDMPs), but little was known about whether PDMPs reduced drug overdose deaths involving benzodiazepines.Design and methodsThis study used a difference-in-difference design with state-quarter aggregate data on drug overdose deaths. The primary data source was Mortality Multiple Cause Files in 1999-2016. Three age-adjusted rates of drug overdose deaths were examined, including those involving benzodiazepines, those involving prescription opioids, and those involving both benzodiazepines and prescription opioids. The policy variables included PDMP data access for benzodiazepines and mandatory use of PDMP data for benzodiazepines. Linear multivariable regressions were used to assess the associations of PDMP policies specific to benzodiazepines with drug overdose death rates, controlling for other state-level policy and socioeconomic factors, state and time fixed effects, and state-specific time trends.ResultsNo significant associations were found between PDMP data access for benzodiazepines and changes in drug overdose death rates involving benzodiazepines and/or prescription opioids. Similarly, no significant associations were found between mandatory use of PDMP data for benzodiazepines and changes in drug overdose death outcomes.Discussion and conclusionsThis study suggested no evidence that PDMP policies specific to benzodiazepines were associated with reduction in benzodiazepine overdose death rates. Future research is warranted to examine detailed features of PDMPs and continuously monitor the impacts of PDMP policies on benzodiazepine-related consequences.
| S-EPMC6641857 | biostudies-literature
Project description:Drug overdose is a public health crisis in the United States, due in part to the unintended consequences of increases in prescribing of opioid analgesics. Many clinicians evaluate risk markers for opioid-related harms when prescribing opioids for chronic pain; however, more data on predictive risk markers are needed. Risk markers are attributes (modifiable and non-modifiable) that are associated with increased probability of an outcome. This review aims to identify risk markers associated with fatal and non-fatal prescription drug overdose by synthesizing findings in the existing peer-reviewed and grey literature. Eligible cohort, case-control, cross-sectional, and case-cohort studies were reviewed and data were extracted for qualitative and quantitative synthesis.Summary odds ratios (SOR) were estimated from 29 studies for six risk markers: sex, age, race, psychiatric disorders, substance use disorder (SUD), and urban/rural residence. Heterogeneity was assessed and effect estimates were stratified by study characteristics. Of the six risk markers identified, SUD had the strongest association with drug overdose death (SOR = 5.24, 95% confidence interval (CI) = 3.53 - 7.76), followed by psychiatric disorders (SOR = 3.94, 95% CI = 3.09 - 5.01), white race (SOR = 2.28, 95% CI = 1.93 - 2.70), the 35-44 year age group relative to the 25-34 year reference group (SOR = 1.52, 95% CI = 1.31 - 1.76), and male sex (SOR = 1.33, 95% CI = 1.17 - 1.51).This review highlights fatal and non-fatal prescription drug risk markers most frequently assessed in peer-reviewed and grey literature. There is a need to better understand modifiable risk markers and underlying reasons for drug misuse in order to inform interventions that may prevent future drug overdoses.
| S-EPMC5545182 | biostudies-other
Project description:BackgroundDrug overdose (OD) deaths in the U.S. continue to rise. After opioids, benzodiazepines (BZD) are the medication most commonly involved in prescription overdoses, yet OD risk factors among those prescribed BZD are not well understood. Our objective was to examine characteristics of BZD, opioid, and other psychotropic prescriptions associated with increased drug OD risk following a BZD prescription.MethodsWe completed a retrospective cohort study using a 20% sample of Medicare beneficiaries with prescription drug coverage. We identified patients with a BZD prescription ("index") claim between 1 April 2016 and 31 December 2017. In the 6 months pre-index, those without and with BZD claims comprised incident and continuing cohorts, which were split by age (incident < 65 [n = 105,737], 65 + [n = 385,951]; continuing < 65 [n = 240,358], 65 + [n = 508,230]). Exposures of interest were: average daily dose and days prescribed of the index BZD; baseline BZD medication possession ratio (MPR) for the continuing cohort; co-prescribed opioids and psychotropics. Our primary outcome was a treated drug OD event (including accidental, intentional, undetermined, or adverse effect) within 30 days of the index BZD, examined using Cox proportional hazards.ResultsAmong incident and continuing BZD cohorts, 0.78% and 0.56% experienced an OD event. Compared to 14-30 days, a < 14-day fill corresponded to higher OD risk in incident (< 65 adjusted hazard ratio [aHR] 1.16 [95% CI 1.03-1.31]; 65 + : aHR 1.21 [CI 1.13-1.30]) and continuing (< 65: aHR 1.33 [CI 1.15-1.53]; 65 + : aHR 1.43 [CI 1.30-1.57]) cohorts. Among continuing users, lower baseline exposure (i.e., MPR < 0.5) was associated with increased OD risk for those < 65 (aHR 1.20 [CI 1.06-1.36]); 65 + (aHR 1.12 [CI 1.01-1.24]). Along with opioids, concurrent antipsychotic use and antiepileptic use were associated with elevated risk of OD in all 4 cohorts (e.g., aHRs for the continuing 65 + cohort: opioid, 1.73 [CI 1.58-1.90]; antipsychotic, 1.33 [CI 1.18-1.50]; antiepileptic, 1.18 [1.08-1.30]).ConclusionsIn both the incident and continuing cohorts, patients dispensed fewer days' supply were at increased OD risk; those in the continuing cohort with more limited baseline BZD exposure were also at elevated risk. Concurrent medication exposures including opioids, antipsychotics, and antiepileptics were associated with short-term elevated OD risk.
| S-EPMC10199543 | biostudies-literature
Project description: Not available
| S-EPMC6549287 | biostudies-literature
Project description:BackgroundConcurrent use of benzodiazepines in opioid users has been linked to a higher risk of an emergency room visit or inpatient admission for opioid overdose and death from drug overdose. Further research is needed to confirm the findings and analyze contributing risk factors for opioid overdoses in a large commercially insured population.ObjectivesTo estimate the risk of opioid overdose associated with opioid users exposed to various combinations of opioid, benzodiazepine, and non-benzodiazepine sedative-hypnotic therapy. To identify other factors that are associated with increased risk for opioid overdose.DesignRetrospective cohort study.PatientsNew start adult users of opioids, defined as naïve to opioids for 6 months, in Kaiser Permanente California regions from January 2013 through September 2017.Main measuresInpatient or emergency department admissions due to opioid-related overdose.Key resultsA total of 2,241,530 patients were included in this study. Patients exposed to opioids, benzodiazepines, and non-benzodiazepine sedative-hypnotics at any point during their follow-up were 60% more likely to overdose than those who were only exposed to opioids (p < 0.0001). Those exposed to opioids and benzodiazepines were 20% more likely to have an opioid-related overdose than those exposed to opioids only (p < 0.0001). Significant risk factors for opioid overdose included exposure to all three medication classes, higher opioid dosage strengths, elderly age (age ≥ 65 years), history of previous overdose, and substance use disorder.ConclusionsResults from this study demonstrate a significant increase in risk of opioid overdose in patients exposed to combinations of sedative-hypnotics with opioids compared to those only taking opioids. Findings from this study provide evidence that opioids should be avoided in combination with benzodiazepines and non-benzodiazepine sedative-hypnotics, used at the lowest dose possible, and used with caution in the elderly, those with previous history of overdose, and those with substance use disorder at baseline.
| S-EPMC7080944 | biostudies-literature
Project description:Background: Drug overdoses (fatal and non-fatal) are among the leading causes of death in population with substance use disorders. The aim of the current study was to identify risk factors for fatal and non-fatal drug overdose for predominantly opioid-dependent treatment-seeking population. Methods: Data were collected from 640 adult patients using a self-reported 25-item Overdose Risk (OdRi) questionnaire pertaining to drug use and identified related domains. The exploratory factor analysis (EFA) was primarily used to improve the interpretability of this questionnaire. Two sets of EFA were conducted; in the first set of analysis, all items were included, while in the second set, items related to the experience of overdose were removed. Logistic regression was used for the assessment of latent factors' association with both fatal and non-fatal overdoses. Results: EFA suggested a three-factor solution accounting for 75 and 97% of the variance for items treated in the first and second sets of analysis, respectively. Factor 1 was common for both sets of EFA analysis, containing six items (Cronbach's α = 0.70) focusing around "illicit drug use and lack of treatment." In the first set of analysis, Factors 2 (Cronbach's α = 0.60) and 3 (Cronbach's α = 0.34) were focusing around "mental health and emotional trauma" and "chronic drug use and frequent overdose" domains, respectively. The increase of Factor 2 was found to be a risk factor for fatal drug overdose (adjusted coefficient = 1.94, p = 0.038). In the second set of analysis, Factors 2 (Cronbach's α = 0.65) and 3 (Cronbach's α = 0.59) as well as Factor 1 were found to be risk factors for non-fatal drug overdose ever occurring. Only Factors 1 and 3 were positively associated with non-fatal overdose (one in a past year). Conclusion: The OdRi tool developed here could be helpful for clinical studies for the overdose risk assessment. However, integrating validated tools for mental health can probably help refining the accuracy of latent variables and the questionnaire's consistency. Mental health and life stress appear as important predictors of both fatal and non-fatal overdoses.
| S-EPMC8506126 | biostudies-literature
Project description: Not available
| S-EPMC9856831 | biostudies-literature
Project description:ImportanceGiven high rates of opioid-related fatal overdoses, improving naloxone access has become a priority. States have implemented different types of naloxone access laws (NALs) and there is controversy over which of these policies, if any, can curb overdose deaths. We hypothesize that NALs granting direct authority to pharmacists to provide naloxone will have the greatest potential for reducing fatal overdoses.ObjectivesTo identify which types of NALs, if any, are associated with reductions in fatal overdoses involving opioids and examine possible implications for nonfatal overdoses.Design, setting, and participantsState-level changes in both fatal and nonfatal overdoses from 2005 to 2016 were examined across the 50 states and the District of Columbia after adoption of NALs using a difference-in-differences approach while estimating the magnitude of the association for each year relative to time of adoption. Policy environments across full state populations were represented in the primary data set. The association for 3 types of NALs was associated: NALs providing direct authority to pharmacists to prescribe, NALs providing indirect authority to prescribe, and other NALs. The study was conducted from January 2017 to January 2019.ExposuresFatal and nonfatal overdoses in states that adopted NAL laws were compared with those in states that did not adopt NAL laws. Further consideration was given to the type of NAL passed in terms of its association with these outcomes. We hypothesize that NALs granting direct authority to pharmacists to provide naloxone will have the greatest potential for reducing fatal overdoses.Main outcomes and measuresFatal overdoses involving opioids were the primary outcome. Secondary outcomes were nonfatal overdoses resulting in emergency department visits and Medicaid naloxone prescriptions.ResultsIn this evaluation of the dispensing of naloxone across the United States, NALs granting direct authority to pharmacists were associated with significant reductions in fatal overdoses, but they may also increase nonfatal overdoses seen in emergency department visits. The effect sizes for fatal overdoses grew over time relative to adoption of the NALs. These policies were estimated to reduce opioid-rated fatal overdoses by 0.387 (95% CI, 0.119-0.656; P = .007) per 100 000 people in 3 or more years after adoption. There was little evidence of an association for indirect authority to dispense (increase by 0.121; 95% CI, -0.014 to 0.257; P = .09) and other NALs (increase by 0.094; 95% CI, -0.040 to 0.227; P = .17).Conclusions and relevanceAlthough many states have passed some type of law affecting naloxone availability, only laws allowing direct dispensing by pharmacists appear to be useful. Communities in which access to naloxone is improved should prepare for increases in nonfatal overdoses and link these individuals to effective treatment.
| S-EPMC6503576 | biostudies-literature
Project description:ObjectivePolicy ramifications of the COVID-19 pandemic shape the concurrent housing and overdose crises in the USA. Housing insecurity is a known risk factor for overdose, yet how residential eviction may influence fatal overdose risk is understudied. We sought to evaluate the spatiotemporal relationship between neighbourhood-level residential eviction rates and overdose mortality in Rhode Island (RI) before and during a statewide eviction moratorium in response to COVID-19.MethodsWe conducted an ecological study at the census tract level in RI (N=240) by modelling the association between quintiles of eviction rates and fatal overdose rates from 2016 to 2021. We applied a Bayesian spatiotemporal approach using an integrated nested Laplace approximation and adjusted for an a priori determined set of time-varying demographic and policy covariates.ResultsDescriptively, we observed a direct, dose-response relationship between quintiles of eviction incidence rates over the full study period and fatal overdose. Prior to the implementation of a statewide eviction moratorium, census tracts in the highest eviction quintile had increased rates of overdose mortality, relative to those in the lowest quintile (posterior mean relative rate = 1.49, 95% credible interval: 1.05 to 2.13). Associations during the periods of eviction moratorium were non-significant.ConclusionThis work highlights the neighbourhood-level relationship between residential eviction and fatal overdose risk in the absence of an eviction moratorium. Enhanced investment in eviction prevention policies, such as rent relief and limitations to the circumstances under which landlords can file for eviction, may complement harm reduction efforts to reduce neighbourhood-level overdose inequalities.
| S-EPMC11812863 | biostudies-literature