Dataset Information

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

ABSTRACT: Importance: 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.

Objective: 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.

Design, setting, and participants: 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.

Exposures: The primary exposure variable was benzodiazepine and opioid coprescriptions. Individuals taking selective serotonin reuptake inhibitors (SSRIs) served as an active comparator reference group.

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

SUBMITTER: Xu KY

PROVIDER: S-EPMC7726637 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Xu Kevin Y KY Hartz Sarah M SM Borodovsky Jacob T JT Bierut Laura J LJ Grucza Richard A RA

JAMA network open 20201201 12

<h4>Importance</h4>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.<h4>Objective</h4>To evaluate whether benzodiazepine use, with or without opioid use, is associated with increased all-cause mortality relative to the ...[more]

PMID: 33295972

Similar Datasets

Project description:Importance:The use of benzodiazepines or alcohol together with opioids increases overdose risk, but characterization of co-involvement by predominant opioid subtype is incomplete to date. Understanding the use of respiratory depressants in opioid overdose deaths (OODs) is important for prevention efforts and policy making. Objective:To assess the prevalence and number of alcohol- or benzodiazepine-involved OODs by opioid subtypes in the United States from 1999 to 2017. Design and Setting:This repeated cross-sectional analysis used data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database of all opioid-involved poisoning deaths from January 1, 1999, to December 31, 2017, for the United States. State-level binge drinking prevalence rates for 2015 to 2017 were obtained from the Behavior Risk Factor Surveillance System of the Centers for Disease Control and Prevention, and benzodiazepine prescribing rates for 2012 (most recent available data) were obtained from IMS Health, a commercial database. Data were analyzed from July 10, 2018, to May 16, 2019. Main Outcomes and Measures:Prevalence of alcohol or benzodiazepine co-involvement for all OODs and by opioid subtype, nationally and by state. Results:From 1999 to 2017, 399 230 poisoning deaths involved opioids, of which 263 601 (66.0%) were male, and 204 560 (51.2%) were aged 35 to 54 years. Alcohol co-involvement for all opioid overdose deaths increased nonlinearly from 12.4% in 1999 to 14.7% in 2017. By opioid subtype, deaths involving heroin and synthetic opioids (eg, fentanyl; excluding methadone) had the highest alcohol co-involvement at 15.5% and 14.9%, respectively, in 2017. Benzodiazepine co-involvement in all OODs increased nonlinearly from 8.7% in 1999 to 21.0% in 2017. Benzodiazepines were present in 33.1% of prescription OODs and 17.1% of synthetic OODs in 2017. State-level rates of binge drinking were significantly correlated with alcohol co-involvement in all OODs (r = 0.34; P = .02). State benzodiazepine prescribing rates were significantly correlated with benzodiazepine co-involvement in all OODs (r = 0.57; P < .001). Conclusions and Relevance:This study found that alcohol and benzodiazepine co-involvement in opioid-involved overdose deaths was common, varied by opioid subtype, and was associated with state-level binge drinking and benzodiazepine prescribing rates. These results may inform state policy initiatives in harm reduction and overdose prevention efforts.

Project description:ObjectiveTo assess variables associated with opioid prescriptions filled perioperatively after hysterectomy and the risk of prolonged opioid use through 1 year after hysterectomy.MethodsIn this retrospective cohort study, we used the 2005-2015 IBM MarketScan databases to identify women aged at least 18 years who underwent hysterectomy. For opioid use, we identified filled prescriptions for opioid medications. We excluded women with prevalent opioid use, defined as an opioid prescription filled 180 to 30 days preoperatively or at least two prescriptions filled in the 30 days before surgery. We defined perioperative opioid use as any opioid prescription filled within 30 days before or 7 days after surgery. We used log-binomial regression to identify independent predictors of perioperative opioid prescription fill. To assess the risk of long-term opioid use, we estimated the proportion of women with ongoing monthly opioid prescriptions through 12 months after surgery and the proportion of women with any opioid prescription 3-6 months after surgery, mimicking published estimates.ResultsAmong 569,634 women who underwent hysterectomy during the study period, 176,537 (30.9%) were excluded owing to prevalent opioid use. We found that 331,322 (84.3%) women filled a perioperative opioid prescription, with median quantity of 30 pills (interquartile range 25-40), and that younger (adjusted risk ratio [adjRR]18-24 0.91) and older (adjRR65-74 0.84; adjRR75+ 0.70) patients were less likely to receive a perioperative prescription compared with women aged 45-54. The proportion of women with continuous monthly fills of opioids through 2, 3, 6, and 12 months after surgery was 1.40%, 0.34%, 0.06%, and 0.02%, respectively.ConclusionMost women who underwent hysterectomy in the United States from 2005 to 2015 filled a perioperative opioid prescription with a median quantity of 30 pills. The risk of prolonged opioid use through 6 months is quite low, at 0.06% or 1 in 1,547.

Project description:ImportanceAs the opioid epidemic evolves, it is vital to identify changes in the geographical distribution of opioid-related deaths, and the specific opioids to which those deaths are attributed, to ensure that federal and state public health interventions remain appropriately targeted.ObjectiveTo identify changes in the geographical distribution of opioid-related mortality across the United States by opioid type.Design, setting, and participantsCross-sectional study using joinpoint modeling and life table analysis of individual-level data from the National Center for Health Statistics on 351?630 US residents who died from opioid-related causes from January 1, 1999, to December 31, 2016, for all of the United States and the District of Columbia. The analysis was conducted from September 6 to November 23, 2018.ExposuresDeaths involving any opioid, heroin, synthetic opioids, and natural and semisynthetic opioids.Main outcomes and measuresOpioid-related mortality rate, annual percent change in the opioid-related mortality rate, and life expectancy lost at age 15 years by state and opioid type.ResultsFrom 1999 to 2016, a total of 231?264 men and 120?366 women died from opioid-related causes across the whole United States. Sixty-six observations were removed owing to missing data on age; therefore, 351?564 US residents were included in this study. The mean (SD) age at death was 39.8 (12.5) years for men and was 43.5 (12.9) years from women. Opioid-related mortality rates, especially from synthetic opioids, rapidly increased in all of the eastern United States. In most states, mortality associated with natural and semisynthetic opioids (ie, prescription painkillers) remained stable. In contrast, 28 states had mortality rates from synthetic opioids that more than doubled every 2 years (ie, annual percent change, ?41%), including 12 with high mortality rates from synthetic opioids (>10 per 100?000 people). Among these 28 states, the mortality rate from natural and semisynthetic opioids ranged from 2.0 to 18.7 per 100?000 people (with a mean mortality rate of 6.0 per 100?000 people). The District of Columbia had the fastest rate of increase in mortality from opioids, more than tripling every year since 2013 (annual percent change, 228.3%; 95% CI, 169.7%-299.6%; P?<?.001), and a high mortality rate from synthetic opioids in 2016 (18.8 per 100?000 people); the mortality rate from natural and semisynthetic opioids was 6.9 per 100?000 people. Nationally, overall opioid-related mortality resulted in 0.36 years of life expectancy lost in 2016, which was 14% higher than deaths due to firearms and 18% higher than deaths due to motor vehicle crashes; 0.17 years of the life expectancy lost was due specifically to synthetic opioids. In 2016, New Hampshire and West Virginia lost more than 1 year of life expectancy due to opioid-related mortality.Conclusions and relevanceOpioid-related mortality, particularly mortality associated with synthetic opioids, has increased in the eastern United States. These findings indicate that policies focused on reducing opioid-related deaths may need to prioritize synthetic opioids and rapidly expanding epidemics in northeastern states and consider the potential for synthetic opioid epidemics outside of the heroin supply.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets