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  1. Fonda, Jennifer R. PhD
  2. Gradus, Jaimie L. DSc
  3. Brogly, Susan B. PhD
  4. McGlinchey, Regina E. PhD
  5. Milberg, William P. PhD
  6. Fredman, Lisa PhD


Objective: To evaluate the association between traumatic brain injury (TBI) and nonfatal opioid overdose, and the role of psychiatric conditions as mediators of this association.


Setting: Post-9/11 veterans receiving care at national Department of Veterans Affairs (VA) facilities from 2007 to 2012.


Participants: In total, 49 014 veterans aged 18 to 40 years receiving long-term opioid treatment of chronic noncancer pain.


Design: Longitudinal cohort study using VA registry data.


Main Measures: TBI was defined as a confirmed diagnosis (28%) according to VA comprehensive TBI evaluation; no TBI was defined as a negative primary VA TBI screen (ie, no head injury). Nonfatal opioid overdose was defined using ICD-9 (International Classification of Diseases, Ninth Revision) codes. We performed demographic-adjusted Cox proportional hazards regression. We quantified the impact of co-occurring and individual psychiatric conditions (mood, anxiety, substance use, and posttraumatic stress disorder) on this association using mediation analyses.


Results: Veterans with TBI had more than a 3-fold increased risk of opioid overdose compared with those without (adjusted hazards ratio [aHR] = 3.22; 95% confidence interval [CI], 2.13-4.89). This association was attenuated in mediation analyses of any co-occurring psychiatric condition (aHR = 1.77; 95% CI, 1.25-2.52) and individual conditions (aHR range, 1.52-2.95).


Conclusion: TBI status, especially in the context of comorbid conditions, should be considered in clinical decisions regarding long-term use of opioids in patients with chronic pain.