Rising rates of unintentional and intentional opioid overdose deaths1 have sharpened interest in probing their association with each other.2 A unified perspective encompasses unintentional and intentional overdoses within self-injury3 and emphasizes shared biological (eg, impulsivity) or social (eg, economic insecurity) risk factors.4 By contrast, a psychological perspective distinguishes the motivation of overdoses as unintentional, intentional, or undetermined intent.5 To evaluate these competing perspectives, we examined mortality following nonfatal opioid overdoses of intentional, unintentional, and undetermined intent. We hypothesized that patients with nonfatal intentional overdoses would be more likely to die by suicide than patients with unintentional overdose while patients with nonfatal unintentional overdoses would be more likely to die of unintentional overdose than suicide.
Statewide California emergency department (ED) visit discharge data from 2009 to 2011 were linked to California death records and analyzed using Stata version 14.0 (StataCorp). Among ED patients with nonfatal opioid drug overdose codes (International Classification of Diseases, Ninth Revision, Clinical Modification codes 965.00 to 965.02 and 965.09), 3 hierarchical cohorts were constructed of patients with nonfatal intentional overdose (codes E950.0 to E952.9), unintentional overdose (codes E850.0 to E869.9), or overdose of undetermined intent (codes E980.0 to E982.9) codes. The Institutional Review Board of University of California, Merced, approved this study with a waiver of informed consent. We calculated 12-month crude mortality rates per 100 000 person-years and 95% CIs during the first 12 months following ED discharge. Deaths were subclassified as unintentional overdose, suicide, all external causes, and natural causes. Annualized standardized mortality rate ratios (SMRs) with 95% CIs were calculated based on 2009 to 2012 California cause-specific mortality rates standardized by sex, age, and race/ethnicity.6 Hazard ratios (HRs) for suicide and unintentional overdose death were estimated using Cox proportional hazard regression adjusting for age, sex, race/ethnicity, and payer.
The sample included 6936 patients with nonfatal intentional opioid overdoses (306 deaths), 16 277 patients with nonfatal unintentional opioid overdoses (1770 deaths), and 5388 patients with nonfatal opioid overdoses of undetermined intent (430 deaths). Patients with nonfatal intentional overdoses included the highest percentage of females and lowest percentage of persons 65 years or older (Table 1). Each nonfatal overdose group had significantly elevated SMRs for natural-cause mortality, suicide, and unintentional overdose death. Suicide SMRs were 76.0 (95% CI, 59.0-93.0) for patients with nonfatal intentional overdoses, 14.5 (95% CI, 9.9-19.0) for patients with unintentional overdoses, and 29.3 (95% CI, 18.0-40.5) for patients with overdoses of undetermined intent. Unintentional overdose SMRs were 66.3 (95% CI, 51.0-81.7) for patients with nonfatal intentional overdoses, 103.3 (95% CI, 91.0-111.5) for patients with unintentional overdoses, and 126.0 (95% CI, 103.0-148.8) for patients with overdoses of undetermined intent (Table 2). In relation to patients with nonfatal unintentional overdoses, adjusted hazards of suicide were significantly greater for patients with nonfatal intentional overdoses (HR, 4.96; 95% CI, 3.34-7.36) and patients with nonfatal overdoses of undetermined intent (HR, 2.18; 95% CI, 1.32-3.60). Compared with patients with nonfatal unintentional overdoses, adjusted hazards of unintentional overdose death were significantly lower for patients with nonfatal intentional overdose (HR, 0.63; 95% CI, 0.48-0.82) but not for patients with nonfatal overdoses of undetermined intent (HR, 1.23; 95% CI, 0.99-1.52).
Following nonfatal opioid overdose, patients were at high risk of mortality from several causes. Suicide risks were greater for patients with nonfatal intentional overdoses compared with unintentional overdoses, while risks of unintentional overdose death were greater for patients with nonfatal unintentional overdoses than intentional overdoses. Shared increased risks for all external-cause mortality across groups support a unified self-injury conceptualization that emphasizes common underlying determinants, while differential mortality risks for suicide and unintentional overdose supports the clinical utility of distinguishing nonfatal overdoses by intent.
Study limitations include potential misclassification related to diagnostic errors in EDs, imprecision in manner of death determinations, and age of the data (from 2009 to 2012), although national fatal intentional opioid overdose rates were nearly constant between 2009 to 2012 and 2017.1 The high risk of unintentional overdose and suicide death following nonfatal opioid overdoses underscore the importance of initiating opioid agonist treatment in the ED for patients with opioid use disorder and performing mental health assessments to evaluate underlying suicide risk.
Accepted for Publication: March 26, 2020.
Corresponding Author: Mark Olfson, MD, MPH, Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, 1051 Riverside Dr, New York, NY 10032 (mo49@cumc.columbia.edu).
Published Online: May 20, 2020. doi:10.1001/jamapsychiatry.2020.1045
Author Contributions: Dr Goldman-Mellor 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.
Study concept and design: All authors.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Olfson, Goldman-Mellor.
Critical revision of the manuscript for important intellectual content: Schoenbaum, Goldman-Mellor.
Statistical analysis: Schoenbaum, Goldman-Mellor.
Obtained funding: Goldman-Mellor.
Conflict of Interest Disclosures: Dr Goldman-Mellor has received grants from the National Institute of Mental Health. No other disclosures were reported.
Funding/Support: This project was funded through grant R15 MH113108 from the National Institute of Mental Health (Dr Goldman-Mellor).
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The views expressed are those of the authors and not necessarily those of the National Institute of Mental Health, the US Department of Health and Human Services, or the federal government.