IMPORTANCE The unprecedented increase in unintentional overdose events that has occurred in tandem with escalating sales of prescription opioids over the past 2 decades has raised concerns about whether the therapeutic use of opioids has contributed to increases in overdose injury. Few controlled studies have examined the extent to which ecologic measures of increases in opioid prescribing and overdose injuries reflect risk among patients prescribed opioids, let alone whether some opioid regimens are safer than others. OBJECTIVE To examine whether the risk of unintentional overdose injury is associated with the duration of opioid action (ie, long-acting vs short-acting formulations). DESIGN, SETTING, AND PARTICIPANTS A propensity score-adjusted cohort study was conducted using population-based health care utilization data from the Veterans Administration Healthcare System. The patients were veterans with chronic painful conditions who began therapy with opioid analgesics between January 1, 2000, and December 31, 2009. MAIN OUTCOMES AND MEASURES Unintentional overdoses that are explicitly coded using International Classification of Disease, Ninth Revision codes as drug or medication poisonings of accidental intent (E850.x-860.x) or undetermined intent (E980.x or drug poisoning [960.x-980.x] without an accompanying external cause of injury code). RESULTS A total of 319 unintentional overdose events were observed. Patients initiating therapy with long-acting opioids were more than twice as likely to overdose compared with persons initiating therapy with short-acting opioids. After adjustment for age, sex, opioid dose, and other clinical characteristics, patients receiving long-acting opioids had a significantly higher rate of overdose injury than did those receiving short-acting opioids (hazard ratio [HR], 2.33; 95% CI, 1.26-4.32). The risk associated with long-acting agents was particularly marked during the first 2 weeks after initiation of treatment (HR, 5.25; 1.88-14.72). CONCLUSIONS AND RELEVANCE To our knowledge, the findings of the present study provide the first evidence that the risk of unintentional overdose injury is related to the prescribed opioid's duration of action. If replicated in other cohorts, our findings suggest that clinicians weighing the benefits and risks of initiating different opioid regimens should consider not only the daily dose prescribed but also the duration of opioid action, favoring short-acting agents whenever possible, especially during the first 2 weeks of therapy.

Understanding the factors that influence veterans’ functional outcome after deployment is critical to provide appropriately targeted care. Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) have been related to disability, but other psychiatric and behavioral conditions are not as well examined. We investigated the impact of deployment-related psychiatric and behavioral conditions on disability among 255 OEF/OIF/OND service members and veterans. Structured clinical interviews assessed TBI and the psychiatric conditions of depression, PTSD, anxiety, and substance use. Self-report questionnaires assessed disability and the behavioral conditions of sleep disturbance and pain. Over 90% of participants had a psychiatric and/or behavioral condition, with approximately half presenting with ≥ 3 conditions. Exploratory factor analysis revealed 4 clinically relevant psychiatric and behavioral factors which accounted for 76.9% of the variance: (a) depression, PTSD, and military mTBI (deployment trauma factor); (b) pain and sleep (somatic factor); (c) anxiety disorders, other than PTSD (anxiety factor); and (d) substance abuse or dependence (substance use factor). Individuals with the conditions comprising the deployment trauma factor were more likely to be substantially disabled than individuals with depression and PTSD, but no military mTBI, OR = 3.52; 95% CI [1.09, 11.37]. Depression, PTSD, and a history of military mTBI may comprise an especially harmful combination associated with high risk for substantial disability.