Long-term opioid therapy for chronic noncancer pain is becoming increasingly common in community practice. Concomitant with this change in practice, rates of fatal opioid overdose have increased. The extent to which overdose risks are elevated among patients receiving medically prescribed long-term opioid therapy is unknown.
To estimate rates of opioid overdose and their association with an average prescribed daily opioid dose among patients receiving medically prescribed, long-term opioid therapy.
Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at the time of overdose.
9940 persons who received 3 or more opioid prescriptions within 90 days for chronic noncancer pain between 1997 and 2005.
Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes—nonfatal and fatal overdoses—were identified through diagnostic codes from inpatient and outpatient care and death certificates and were confirmed by medical record review.
51 opioid-related overdoses were identified, including 6 deaths. Compared with patients receiving 1 to 20 mg/d of opioids (0.2% annual overdose rate), patients receiving 50 to 99 mg/d had a 3.7-fold increase in overdose risk (95% CI, 1.5 to 9.5) and a 0.7% annual overdose rate. Patients receiving 100 mg/d or more had an 8.9-fold increase in overdose risk (CI, 4.0 to 19.7) and a 1.8% annual overdose rate.
Increased overdose risk among patients receiving higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation.
Patients receiving higher doses of prescribed opioids are at increased risk for overdose, which underscores the need for close supervision of these patients.
Primary Funding Source:
National Institute of Drug Abuse.
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Author, Article, and Disclosure Information
Kate M. Dunn,
From Group Health Research Institute and University of Washington, Seattle, Washington; Arthritis Research Campaign National Primary Care Centre, Keele University, Keele, United Kingdom; and Northern California Kaiser Permanente, Oakland, and University of California, San Francisco, California.
Disclaimer: Dr. Von Korff had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Grant Support: This research was supported by a grant to Dr. Von Korff from the National Institute of Drug Abuse (DA022557). Dr. Dunn participated in this work with Dr. Von Korff at the Group Health Research Institute through a grant from the Wellcome Trust (083572).
Disclosures:Consultancies: M.D. Sullivan (Eli Lilly, ABT Bio-Pharma). Stock ownership or options (other than mutual funds): K.W. Saunders (Merck & Co.). Grants received: M.D. Sullivan (Wyeth, Eli Lilly, Aetna, Johnson & Johnson, Ortho-McNeil). Grants pending: M. Von Korff (Johnson & Johnson).
Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Von Korff (e-mail, vonkorff.
Corresponding Author: Michael Von Korff, ScD, Group Health Research Institute, Group Health Cooperative, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101; e-mail, vonkorff.
Current Author Addresses: Dr. Dunn: Arthritis Research Campaign National Primary Care Centre, Primary Care Sciences, Keele University, Keele ST5 5BG, United Kingdom.
Ms. Saunders and Dr. Rutter: Group Health Research Institute, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448.
Dr. Banta-Green: Alcohol and Drug Abuse Institute, University of Washington, 1107 Northeast 45th Street, Suite 120, Box 354805, Seattle, WA 98105-4631.
Dr. Merrill: Department of Medicine, RR-512, Health Sciences Building, University of Washington, Box 356420, Seattle, WA 98195-6420.
Dr. Sullivan: Department of Psychiatry & Behavioral Sciences, University of Washington, 1959 Northeast Pacific Street, Box 356560, Room BB1644, Seattle, WA 98195-6560.
Drs. Weisner, Silverberg, and Campbell: Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612.
Dr. Psaty: Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Metropolitan Park East Tower, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101.
Dr. Von Korff: Group Health Research Institute, Group Health Cooperative, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101.
Author Contributions: Conception and design: K.M. Dunn, K.W. Saunders, C.M. Rutter, C.J. Banta-Green, J.O. Merrill, C.M. Weisner, C.I. Campbell, M. Von Korff.
Analysis and interpretation of the data: K.M. Dunn, K.W. Saunders, C.M. Rutter, C.J. Banta-Green, J.O. Merrill, M.D. Sullivan, M.J. Silverberg, C.I. Campbell, B.M. Psaty, M. Von Korff.
Drafting of the article: K.M. Dunn, M.D. Sullivan, M Von Korff.
Critical revision of the article for important intellectual content: K.M. Dunn, K.W. Saunders, C.M. Rutter, C.J. Banta-Green, J.O. Merrill, M.D. Sullivan, C.M. Weisner, M.J. Silverberg, C.I. Campbell, B.M. Psaty, M. Von Korff.
Final approval of the article: K.M. Dunn, K.W. Saunders, C.M. Rutter, C.J. Banta-Green, J.O. Merrill, M.D. Sullivan, C.M. Weisner, M.J. Silverberg, C.I. Campbell, B.M. Psaty, M. Von Korff.
Statistical expertise: C.M. Rutter, B.M. Psaty.
Obtaining of funding: C.M. Weisner, C.I. Campbell, M. Von Korff.
Administrative, technical, or logistic support: K.W. Saunders.
Collection and assembly of data: K.M. Dunn, K.W. Saunders, M. Von Korff.