The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain
Open accessAbstract
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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“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]
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Cites
CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016
Dowell, D., Haegerich, T. M., & Chou, R. (2016) · JAMA · doi:10.1001/jama.2016.1464 · Cited by 5,161
Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis
Finnerup, N. B., Attal, N., Haroutounian, S., McNicol, E., Baron, R., Dworkin, R. H., Gilron, I., Haanpää, M., Hansson, P., Jensen, T. S., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70251-0 · Cited by 3,980
Survival analysis using sas®: a practical guide
Allison, P. D. (1995) · International Linear Collider · Cited by 3,570
Evaluating medication effects outside of clinical trials: new-user designs
Ray, W. A. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg231 · Cited by 1,646
Chou, R., Turner, J. A., Devine, E. B., Hansen, R. N., Sullivan, S. D., Blazina, I., Dana, T., Bougatsos, C., & Deyo, R. A. (2015) · Annals of Internal Medicine · doi:10.7326/m14-2559 · Cited by 1,606
Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths
Bohnert, A. S. B. (2011) · JAMA · doi:10.1001/jama.2011.370 · Cited by 1,509
Vital signs: overdoses of prescription opioid pain relievers---United States, 1999--2008.
Paulozzi, L. J., Jones, C. M., Mack, K. A., & Rudd, R. A. (2011) · PubMed · Cited by 1,350
Opioid Prescriptions for Chronic Pain and Overdose
Dunn, K. M., Saunders, K. W., Rutter, C. M., Banta‐Green, C. J., Merrill, J. O., Sullivan, M. D., Weisner, C. M., Silverberg, M. J., Campbell, C. I., Psaty, B. M., et al. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-152-2-201001190-00006 · Cited by 1,265
Opioid Therapy for Chronic Pain
Ballantyne, J. C., & Mao, J. (2003) · New England Journal of Medicine · doi:10.1056/nejmra025411 · Cited by 960
A Flood of Opioids, a Rising Tide of Deaths
Okie, S. (2010) · New England Journal of Medicine · doi:10.1056/nejmp1011512 · Cited by 832
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Colloca, L., Ludman, T., Bouhassira, D., Baron, R., Dickenson, A. H., Yarnitsky, D., Freeman, R. L., Truini, A., Attal, N., Finnerup, N. B., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.2 · Cited by 2,253
CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022
Dowell, D., Ragan, K. R., Jones, C. M., Baldwin, G. T., & Chou, R. (2022) · MMWR. Recommendations and Reports · doi:10.15585/mmwr.rr7103a1 · Cited by 1,886
Krebs, E. E., Gravely, A., Nugent, S., Jensen, A. C., DeRonne, B., Goldsmith, E. S., Kroenke, K., Bair, M. J., & Noorbaloochi, S. (2018) · JAMA · doi:10.1001/jama.2018.0899 · Cited by 983
Opioids for Chronic Noncancer Pain
Busse, J. W., Wang, L., Kamaleldin, M., Craigie, S., Riva, J. J., Montoya, L., Mulla, S. M., Lopes, L. C., Vogel, N., Chen, E., et al. (2018) · JAMA · doi:10.1001/jama.2018.18472 · Cited by 766
Epidemiology of cardiovascular disease in young individuals
Andersson, C., & Vasan, R. S. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.154 · Cited by 760
Metadata
- Authors
- Ray, W. A., Chung, C. P., Murray, K. T., Hall, K., & Stein, C. M.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Ray, Wayne A.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2016-06-14
- Volume
- 315
- Issue
- 22
- Pages
- 2415
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- 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
- FWCI
- 52.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- 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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