Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study

Autor: C. Michael Stein, Beth A. Malow, James R. Daugherty, Katherine T. Murray, Wayne A. Ray, Cecilia P. Chung
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Epidemiology
Physiology
Nonbenzodiazepine
Social Sciences
Cardiovascular Medicine
Hypnotic
Benzodiazepines
0302 clinical medicine
Medical Conditions
Medicine and Health Sciences
Hypnotics and Sedatives
030212 general & internal medicine
Aged
80 and over
Analgesics
Mortality rate
Hazard ratio
Drugs
General Medicine
Substance abuse
Analgesics
Opioid
Neurology
Cardiovascular Diseases
Cohort
Medicine
Drug Therapy
Combination
Female
medicine.drug
Research Article
medicine.medical_specialty
Prescription Drugs
Insomnia
medicine.drug_class
Death Rates
Political Science
Cardiology
Public Policy
Medicare
03 medical and health sciences
Population Metrics
Internal medicine
medicine
Humans
Pain Management
Mortality
Aged
Retrospective Studies
Pharmacology
Population Biology
business.industry
Trazodone
Biology and Life Sciences
Retrospective cohort study
Cardiovascular Disease Risk
medicine.disease
United States
Dyssomnias
Opioids
Medical Risk Factors
business
Sleep Disorders
Physiological Processes
Sleep
030217 neurology & neurosurgery
Zdroj: PLoS Medicine, Vol 18, Iss 7, p e1003709 (2021)
PLoS Medicine
ISSN: 1549-1676
1549-1277
Popis: Background Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg. Methods and findings The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score–stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables. Conclusions In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine–opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.
In a retrospective cohort study, Dr. Wayne Ray and colleagues investigate concurrent opioid and hypnotic use and mortality in older adults in US.
Author summary Why was this study done? Benzodiazepines and the related z-drugs are sleep medications commonly prescribed for persons 65 years of age or older. Both can interfere with breathing, which, in turn, may cause irregular heartbeat and deaths. Opioid painkillers, often used with sleep medications, also interfere with breathing and thus could increase the likelihood of deaths with benzodiazepines or z-drugs. Trazodone, an antidepressant that in low doses often is prescribed for insomnia, has not been found to affect breathing and thus may be safer for older patients, particularly for those also taking opioids. What did the researchers do and find? We identified 400,924 persons in the US Medicare program 65 or older who began treatment with benzodiazepine, z-drug, or trazodone sleep medications. For patients without and with opioid use, we compared the rate of out-of-hospital deaths—often related to heart problems—and total mortality during treatment with benzodiazepines and z-drugs to that for trazodone. For patients with opioid exposure, benzodiazepines were associated with respective 302% and 221% increases in out-of-hospital and total mortality, and z-drugs were associated with respective 98% and 65% increases in out-of-hospital and total mortality. What do these findings mean? In older populations, the risks of concurrent benzodiazepine–opioid exposure go beyond the known increased likelihood of overdose, suggesting that greater efforts are needed to prevent use of this medication combination. Patients and clinicians should be aware that in combination with opioids, the z-drugs, thought to be relatively safe, may increase the risk of death.
Databáze: OpenAIRE
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