Association Between Benzodiazepine Use With or Without Opioid Use and All-Cause Mortality in the United States, 1999-2015.
Analgesics, Opioid
/ therapeutic use
Benzodiazepines
/ therapeutic use
Chronic Disease
/ epidemiology
Cohort Studies
Comorbidity
Drug Therapy, Combination
/ mortality
Female
Humans
Male
Mental Disorders
/ drug therapy
Middle Aged
Mortality
Practice Patterns, Physicians'
/ trends
Prescription Drugs
/ therapeutic use
Proportional Hazards Models
Retrospective Studies
Risk Factors
United States
/ epidemiology
Journal
JAMA network open
ISSN: 2574-3805
Titre abrégé: JAMA Netw Open
Pays: United States
ID NLM: 101729235
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
entrez:
9
12
2020
pubmed:
10
12
2020
medline:
30
1
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33295972
pii: 2773826
doi: 10.1001/jamanetworkopen.2020.28557
pmc: PMC7726637
doi:
Substances chimiques
Analgesics, Opioid
0
Prescription Drugs
0
Benzodiazepines
12794-10-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2028557Subventions
Organisme : NIAAA NIH HHS
ID : U10 AA008401
Pays : United States
Organisme : NIDA NIH HHS
ID : K12 DA041449
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA044744
Pays : United States
Organisme : NIMH NIH HHS
ID : R25 MH112473
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA036583
Pays : United States
Organisme : NIAAA NIH HHS
ID : F32 AA027941
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA025689
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA024888
Pays : United States
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