Sex-Specific Associations Between Deployment-Related Traumatic Brain Injury and Nonfatal Drug Overdose Among a National Cohort of Post-9/11 Veterans

Objective: To determine whether there are sex-specific associations between traumatic brain injury (TBI) and nonfatal drug overdose, when considering psychiatric conditions as mediators of this association. Setting: Veterans receiving care at national Department of Veterans Affairs (VA) facilities from April 2007 to December 2019. Participants: 1 231 406 post-9/11 veterans aged 18 to 65, with 11.0% males and 2.9% females with confirmed TBI. Design: Retrospective, longitudinal cohort study using VA medical record data. Main Measures: Deployment-related TBI was defined as a confirmed diagnosis according to the VA TBI comprehensive evaluation; no deployment-related TBI was defined as no deployment-related head injury. Nonfatal overdose (any drug, and opioid-specific) were defined using International Classification of Diseases, Ninth and Tenth Revision codes. We performed sex-specific Cox-proportional hazards regressions for any drug and opioid overdose outcomes, adjusted for demographic and military characteristics. Mediation analyses were conducted to examine the role of psychiatric conditions (substance use, anxiety, mood, and posttraumatic stress disorders). Results: Compared to veterans without TBI, veterans with a history of TBI had approximately a 2-fold increased adjusted rate of any drug overdose (males: adjusted hazards ratio [aHR] = 1.93, 95% confidence interval [CI] = 1.84, 2.03; females: aHR = 1.82, 95% CI = 1.56, 2.12) and over a 2-fold increased adjusted rate of opioid-related overdose (males: aHR = 2.29, 95% CI = 2.03, 2.59; females: aHR = 2.43, 95% CI = 1.58, 3.74). The associations were partially attributable to comorbid psychiatric conditions, yet remained present after adjustment, for any drug overdose (males: aHR range, 1.38-1.86; females: aHR range, 1.45-1.89) and opioid-specific overdose (males: aHR range, 1.58–2.15; females: aHR range, 1.56-2.80) outcomes. Conclusions: Veterans with deployment-related TBIs have a higher rate of nonfatal overdose, with similar associations for males and females. The associations were partially attributable to, but not fully explained by, comorbid psychiatric conditions.