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Cited by 369Opioid Use Disorder TreatmentPain Management and Opioid UsePharmaceutical Practices and Patient Outcomes

Prescription of long-acting opioids and mortality in patients with chronic noncancer pain

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Ray, Wayne A., Chung, Cecilia P., Murray, Katherine T., Hall, Kathi, Stein, C. Michael·2016·JAMA
DOI 10.1001/jama.2016.7789PMC PMC5030814
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Abstract

IMPORTANCE: Long-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes. OBJECTIVE: To compare all-cause mortality for patients with chronic noncancer pain who were prescribed either long-acting opioids or alternative medications for moderate to severe chronic pain. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care. EXPOSURES: Propensity score-matched new episodes of prescribed therapy for long-acting opioids or either analgesic anticonvulsants or low-dose cyclic antidepressants (control medications). MAIN OUTCOMES AND MEASURES: Total and cause-specific mortality as determined from death certificates. Adjusted hazard ratios (HRs) and risk differences (difference in incidence of death) were calculated for long-acting opioid therapy vs control medication. RESULTS: There were 22,912 new episodes of prescribed therapy for both long-acting opioids and control medications (mean [SD] age, 48 [11] years; 60% women). The long-acting opioid group was followed up for a mean 176 days and had 185 deaths and the control treatment group was followed up for a mean 128 days and had 87 deaths. The HR for total mortality was 1.64 (95% CI, 1.26-2.12) with a risk difference of 68.5 excess deaths (95% CI, 28.2-120.7) per 10,000 person-years. Increased risk was due to out-of-hospital deaths (154 long-acting opioid, 60 control deaths; HR, 1.90; 95% CI, 1.40-2.58; risk difference, 67.1; 95% CI, 30.1-117.3) excess deaths per 10,000 person-years. For out-of-hospital deaths other than unintentional overdose (120 long-acting opioid, 53 control deaths), the HR was 1.72 (95% CI, 1.24-2.39) with a risk difference of 47.4 excess deaths (95% CI, 15.7-91.4) per 10,000 person-years. The HR for cardiovascular deaths (79 long-acting opioid, 36 control deaths) was 1.65 (95% CI, 1.10-2.46) with a risk difference of 28.9 excess deaths (95% CI, 4.6-65.3) per 10,000 person-years. The HR during the first 30 days of therapy (53 long-acting opioid, 13 control deaths) was 4.16 (95% CI, 2.27-7.63) with a risk difference of 200 excess deaths (95% CI, 80-420) per 10,000 person-years. CONCLUSIONS AND RELEVANCE: Prescription of long-acting opioids for chronic noncancer pain, compared with anticonvulsants or cyclic antidepressants, was associated with a significantly increased risk of all-cause mortality, including deaths from causes other than overdose, with a modest absolute risk difference. These findings should be considered when evaluating harms and benefits of treatment.

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  • Long-term opioid treatment increases the risk of death due to unintentional overdose and cardiorespiratory problems.

    “It has been found that the use of long-term opioid treatment increases the risk of death due to unintentional overdose and cardiorespiratory problems [5].”

    From Pain acceptance creates an emotional context that protects against the misuse of prescription opioids: A study in a sample of patients with chronic noncancer pain (2021) · cites this paper as [5]

    The Results report higher cardiovascular mortality among patients prescribed long-acting opioids, and the Discussion says the elevated risk was not confined to unintentional overdose deaths. But the study concerns long-acting opioids, not necessarily long-term treatment: the Discussion says the increased mortality was confined to the first 180 days. It also proposes respiratory effects as a possible explanation for cardiovascular deaths rather than establishing increased deaths from cardiorespiratory problems as a combined category. (LLM, conf=0.88)

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Authors
Ray, W. A., Chung, C. P., Murray, K. T., Hall, K., & Stein, C. M.
Affiliations
Vanderbilt University (US)
Corresponding author
Ray, Wayne A.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2016-06-14
Volume
315
Issue
22
Pages
2415
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2016.7789
PMC
PMC5030814
OpenAlex
W2429408914
Cited by
369
References
44
Citations by year
2026: 10 · 2025: 21 · 2024: 23 · 2023: 25 · 2022: 29 · 2021: 41 · 2020: 57 · 2019: 48 · 2018: 56 · 2017: 41 · 2016: 15 · 2014: 1 · 2013: 1
FWCI
52.88
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Rheumatology Research Foundation
  • National Heart, Lung, and Blood Institute (R01HL081707)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23AR064768)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
Keywords
long-acting opioids, chronic non-cancer pain, all-cause mortality, out-of-hospital death, opioid overdose, Medicaid patients, opioid prescribing, cardiovascular mortality, respiratory mortality
MeSH terms
Analgesics, Opioid, Anticonvulsants, Antidepressive Agents, Cardiovascular Diseases, Cause of Death, Female, Fentanyl, Humans, Male, Methadone, Middle Aged, Morphine, Oxycodone, Drug Prescriptions, Retrospective Studies, Risk, Proportional Hazards Models, Propensity Score, Chronic Pain, Drug Overdose

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