Background:
Nonfatal opioid overdose is an opportunity to identify and treat substance use disorders, but treatment patterns after the overdose are unknown.
Objective:
To determine prescribed opioid dosage after an opioid overdose and its association with repeated overdose.
Design:
Retrospective cohort study.
Setting:
A large U.S. health insurer.
Participants:
2848 commercially insured patients aged 18 to 64 years who had a nonfatal opioid overdose during long-term opioid therapy for noncancer pain between May 2000 and December 2012.
Measurements:
Nonfatal opioid overdose was identified using International Classification of Diseases, Ninth Revision, Clinical Modification, codes from emergency department or inpatient claims. The primary outcome was daily morphine-equivalent dosage (MED) of opioids dispensed from 60 days before to up to 730 days after the index overdose. We categorized dosages as large (≥100 mg MED), moderate (50 to <100 mg MED), low (<50 mg MED), or none (0 mg MED). Secondary outcomes included time to repeated overdose stratified by daily dosage as a time-varying covariate.
Results:
Over a median follow-up of 299 days, opioids were dispensed to 91% of patients after an overdose. Seven percent of patients (n = 212) had a repeated opioid overdose. At 2 years, the cumulative incidence of repeated overdose was 17% (95% CI, 14% to 20%) for patients receiving high dosages of opioids after the index overdose, 15% (CI, 10% to 21%) for those receiving moderate dosages, 9% (CI, 6% to 14%) for those receiving low dosages, and 8% (CI, 6% to 11%) for those receiving no opioids.
Limitation:
The cohort was limited to commercially insured adults.
Conclusion:
Almost all patients continue to receive prescription opioids after an overdose. Opioid discontinuation after overdose is associated with lower risk for repeated overdose.
Primary Funding Source:
Health Resources and Services Administration.
References
- 1.
Caudill-Slosberg MA ,Schwartz LM , andWoloshin S . Office visits and analgesic prescriptions for musculoskeletal pain in U.S.: 1980 vs. 2000. Pain. 2004;109:514-9. [PMID: 15157714] CrossrefMedlineGoogle Scholar - 2.
Boudreau D ,Von Korff M ,Rutter CM ,Saunders K ,Ray GT ,Sullivan MD ,et al . Trends in long-term opioid therapy for chronic non-cancer pain. Pharmacoepidemiol Drug Saf. 2009;18:1166-75. [PMID: 19718704] CrossrefMedlineGoogle Scholar - 3.
Sullivan MD ,Edlund MJ ,Fan MY ,Devries A ,Brennan Braden J , andMartin BC . Trends in use of opioids for non-cancer pain conditions 2000–2005 in commercial and Medicaid insurance plans: the TROUP study. Pain. 2008;138:440-9. [PMID: 18547726] CrossrefMedlineGoogle Scholar - 4.
Jones CM ,Mack KA , andPaulozzi LJ . Pharmaceutical overdose deaths, United States, 2010. JAMA. 2013;309:657-9. [PMID: 23423407] CrossrefMedlineGoogle Scholar - 5.
Centers for Disease Control and Prevention (CDC) . Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. MMWR Morb Mortal Wkly Rep. 2011;60:1487-92. [PMID: 22048730] MedlineGoogle Scholar - 6.
Centers for Disease Control and Prevention (CDC) . Emergency department visits involving nonmedical use of selected prescription drugs – United States, 2004–2008. MMWR Morb Mortal Wkly Rep. 2010;59:705-9. [PMID: 20559200] MedlineGoogle Scholar - 7.
Manchikanti L ,Abdi S ,Atluri S ,Balog CC ,Benyamin RM ,Boswell MV ,et al .American Society of Interventional Pain Physicians . American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2—guidance. Pain Physician. 2012;15:S67-116. [PMID: 22786449] MedlineGoogle Scholar - 8.
Chou R ,Fanciullo GJ ,Fine PG ,Adler JA ,Ballantyne JC ,Davies P ,et al .American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel . Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10:113-30. [PMID: 19187889] CrossrefMedlineGoogle Scholar - 9.
Dunn KM ,Saunders KW ,Rutter CM ,Banta-Green CJ ,Merrill JO ,Sullivan MD ,et al . Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152:85-92 LinkGoogle Scholar - 10.
Bohnert AS ,Valenstein M ,Bair MJ ,Ganoczy D ,McCarthy JF ,Ilgen MA ,et al . Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305:1315-21. [PMID: 21467284] CrossrefMedlineGoogle Scholar - 11. Injury Surveillance Workgroup 7. Consensus Recommendations for National and State Poisoning Surveillance. Atlanta, GA: The Safe States Alliance; 2012. Accessed at www.safestates.org/resource/resmgr/imported/ISW7%20Full%20Report_3.pdf on 22 June 2015. Google Scholar
- 12.
Unick GJ ,Rosenblum D ,Mars S , andCiccarone D . Intertwined epidemics: national demographic trends in hospitalizations for heroin- and opioid-related overdoses, 1993–2009. PLoS One. 2013;8:e54496. [PMID: 23405084] CrossrefMedlineGoogle Scholar - 13.
Walley AY ,Xuan Z ,Hackman HH ,Quinn E ,Doe-Simkins M ,Sorensen-Alawad A ,et al . Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013;346:f174. [PMID: 23372174] CrossrefMedlineGoogle Scholar - 14.
Von Korff M ,Korff MV ,Saunders K ,Thomas Ray G ,Boudreau D ,Campbell C ,et al . De facto long-term opioid therapy for noncancer pain. Clin J Pain. 2008;24:521-7. [PMID: 18574361] CrossrefMedlineGoogle Scholar - 15.
Mattick RP ,Breen C ,Kimber J , andDavoli M . Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;2:CD002207. [PMID: 24500948] MedlineGoogle Scholar - 16.
Snapinn SM ,Jiang Q , andIglewicz B . Illustrating the impact of a time-varying covariate with an extended Kaplan–Meier estimator. Am Stat. 2005;59:301-7. CrossrefGoogle Scholar - 17.
Edlund MJ ,Steffick D ,Hudson T ,Harris KM , andSullivan M . Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain. 2007;129:355-62. [PMID: 17449178] CrossrefMedlineGoogle Scholar - 18.
Ives TJ ,Chelminski PR ,Hammett-Stabler CA ,Malone RM ,Perhac JS ,Potisek NM ,et al . Predictors of opioid misuse in patients with chronic pain: a prospective cohort study. BMC Health Serv Res. 2006;6:46. [PMID: 16595013] CrossrefMedlineGoogle Scholar - 19.
Edlund MJ ,Martin BC ,Fan MY ,Devries A ,Braden JB , andSullivan MD . Risks for opioid abuse and dependence among recipients of chronic opioid therapy: results from the TROUP study. Drug Alcohol Depend. 2010;112:90-8. [PMID: 20634006] CrossrefMedlineGoogle Scholar - 20.
Boscarino JA ,Rukstalis M ,Hoffman SN ,Han JJ ,Erlich PM ,Gerhard GS ,et al . Risk factors for drug dependence among out-patients on opioid therapy in a large U.S. health-care system. Addiction. 2010;105:1776-82. [PMID: 20712819] CrossrefMedlineGoogle Scholar - 21.
Centers for Disease Control and Prevention (CDC) . Overdose deaths involving prescription opioids among Medicaid enrollees – Washington, 2004–2007. MMWR Morb Mortal Wkly Rep. 2009;58:1171-5. [PMID: 19875978] MedlineGoogle Scholar - 22.
Bohnert AS ,Ilgen MA ,Galea S ,McCarthy JF , andBlow FC . Accidental poisoning mortality among patients in the Department of Veterans Affairs Health System. Med Care. 2011;49:393-6. [PMID: 21407033] CrossrefMedlineGoogle Scholar - 23.
Garcia AM . State laws regulating prescribing of controlled substances: balancing the public health problems of chronic pain and prescription painkiller abuse and overdose. J Law Med Ethics. 2013;41 Suppl 1:42-5. [PMID: 23590739] CrossrefMedlineGoogle Scholar - 24.
Daubresse M ,Gleason PP ,Peng Y ,Shah ND ,Ritter ST , andAlexander GC . Impact of a drug utilization review program on high-risk use of prescription controlled substances. Pharmacoepidemiol Drug Saf. 2014;23:419-27. [PMID: 23881609] doi:10.1002/pds.3487 CrossrefMedlineGoogle Scholar
Author, Article and Disclosure Information
Grant Support: Dr. Larochelle was supported by the Health Resources and Services Administration (grants T32 HP10251 and T32 HP12706), Ryoichi Sasakawa Fellowship Fund, and Harvard Pilgrim Health Care Institute.
Disclosures: Dr. Larochelle reports grants from the Health Resources and Services Administration and Ryoichi Sasakawa Fellowship Fund and nonfinancial support from the Harvard Pilgrim Health Care Institute during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0038.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Statistical code: Available from Dr. Larochelle (e-mail, marc.larochelle[email protected]). Study protocol and data set: Not available.
Corresponding Author: Marc R. Larochelle, MD, MPH, Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118; e-mail, [email protected].
Current Author Addresses: Drs. Larochelle and Liebschutz: Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118.
Dr. Zhang, Mr. Ross-Degnan, and Mr. Wharam: Department of Population Medicine, Harvard Medical School, 133 Brookline Avenue, 6th Floor, Boston, MA 02215.
Author Contributions: Conception and design: M.R. Larochelle, J.M. Liebschutz, D. Ross-Degnan, J.F. Wharam.
Analysis and interpretation of the data: M.R. Larochelle, J.M. Liebschutz, D. Ross-Degnan.
Drafting of the article: M.R. Larochelle, J.F. Wharam.
Critical revision of the article for important intellectual content: M.R. Larochelle, J.M. Liebschutz, F. Zhang, D. Ross-Degnan, J.F. Wharam.
Final approval of the article: M.R. Larochelle, J.M. Liebschutz, F. Zhang, D. Ross-Degnan, J.F. Wharam.
Statistical expertise: F. Zhang.
Obtaining of funding: J.F. Wharam.
Administrative, technical, or logistic support: M.R. Larochelle, J.F. Wharam.
Collection and assembly of data: M.R. Larochelle, J.F. Wharam.

Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated.