Abstract
Deaths associated with the co-prescribing of opioid and benzodiazepine pharmacotherapies have raised concerns among health care providers, federal agencies, and the public. The U.S. Congress has expressed concerns particularly about this issue in the veteran population. Veterans are more likely than non-veterans to experience pain, trauma, and mental health conditions from training and combat-related service and be prescribed pharmacotherapies for treatment. Congress mandated that the Department of Veterans Affairs (VA) request an ad hoc committee of the National Academies of Sciences, Engineering, and Medicine (the National Academies) be assembled to evaluate the effects of prescribed opioid and benzodiazepine pharmacotherapies on all-cause mortality of U.S. veterans, including suicide, focusing on practices between 2007 and 2019. The committee applied causal inference methodology and leveraged large VA and Veterans Health Administration (VHA) datasets (e.g., health care, clinical, and administrative data), Centers for Medicare and Medicaid Services data, and the National Death Index to conduct its work. Based on the study findings, the committee concludes the following on all-cause mortality and suicide mortality in veterans who received care from the VHA 2007–2019:
Conclusions 1–2. The committee concludes that there is an increased risk of all-cause mortality among veterans newly dispensed opioid pharmacotherapy compared to those newly dispensed non-opioid pain pharmacotherapy and that there is an increased risk of all-cause mortality among veterans co-prescribed opioid and benzodiazepine pharmacotherapies compared to those co-prescribed non-opioid pain and benzodiazepine pharmacotherapies or to those co-prescribed opioid and alternative non-benzodiazepine pharmacotherapies.
Conclusions 3–4. The committee concludes that there is an increased risk of all-cause mortality among veterans who initiated opioid treatment at higher dosage levels compared to lower levels and that there is an increased risk of all-cause mortality among veterans whose treatment strategy was either slow or fast opioid dosage escalation compared to stable dosage.
Conclusion 5. The committee concludes that there is an increased risk of suicide mortality among veterans newly dispensed opioid pharmacotherapy compared to those newly dispensed non-opioid pain pharmacotherapy.
Conclusion 6. The committee concludes there is no evidence of a difference in the risk of suicide mortality among veterans newly dispensed opioid pharmacotherapy and currently dispensed benzodiazepine pharmacotherapy compared to those newly dispensed non-opioid pain pharmacotherapy and currently dispensed benzodiazepine pharmacotherapy.
Conclusion 7. The committee concludes that there is some evidence of a higher risk of suicide mortality among veterans co-prescribed opioid and benzodiazepine pharmacotherapy, although the estimate is imprecise at 3 months.
Conclusion 8. Given the lower number of suicide deaths in the eligible population the committee is unable to conduct analyses to address the question of the effect of different opioid dosage treatment strategies on suicide mortality.
Overall, the committee’s findings are consistent with concerns regarding the initiation of opioid pharmacotherapy and the concurrent prescribing of benzodiazepine pharmacotherapy. Specifically, concerns about both the prescribing of opioids and the interaction between opioid and benzodiazepine pharmacotherapies appear in VA/Department of Defense clinical practice guidelines in 2010, 2017, and 2022. It is important to note that the committee’s interpretation of the results, which occurred in the past, is not intended to influence restriction for any medication nor is it to be viewed as an absolute contraindication for the clinical use of benzodiazepines with opioids.
