Abstract
Introduction: the CDC guidelines of 2016 and 2022 strongly proscribed the co-prescription of opioids and benzodiazepines, implicitly suggesting that the combination was associated with high risk. This position now strongly influences health provider organizations, clinicians, pharmacies, health insurance companies, and boards of medicine. We have previously comprehensively reviewed the generally high-quality published studies, all employing a retrospective cohort design. These studies suggest that, to the extent that the combination increases mortality risk, the magnitude of the increase is small and it likely reflects a conflation of mortality risk related to the underlying conditions and the risks associated with simultaneous use of drugs of both classes. We here recapitulate the results of our prior analyses, contrast them with CDC positions, and introduce the results of additional studies, some only recently published and some of which we had previously been unaware.
Methods: Analytic review of the scientific literature.
Results and Discussion: Studies previously analyzed by us focused exclusively on risks associated with co-prescription. The results of further studies, reviewed here, suggest that, while there are small populations in whom co-prescription, or even solely prescription of benzodiazepines, may be risky, risks of morbid outcomes in clinic populations in general are dominated by the impact of psychiatric disease and opioids make a very small and indirect contribution. A recently published study has demonstrated the very high mortality risk associated with tapering and discontinuing benzodiazepines. Our modest proposal bears on the importance of applying a deeper understanding of published papers and the de facto meaning of the cited risk factors for death.
Conclusion: There has been substantial misconstrual of association with causation. Opioids and benzodiazepines have emerged as, at worst, very minor contributors to mortality and may often be better viewed as markers of the disorders that actually cause excess deaths: psychiatric disease and undertreatment of physical pain.