HealthDay News — Coprescription of benzodiazepines and opioid agonist treatment (OAT) is associated with an increased risk for drug-related poisoning (DRP) mortality in opioid-dependent individuals, according to a study published online Nov. 26 in PLOS Medicine.

John Macleod, M.B., Ch.B., Ph.D., from University of Bristol in the United Kingdom, and colleagues analyzed data from the U.K. Clinical Practice Research Datalink (12,118 patients aged 15 to 64 years) prescribed OAT between 1998 and 2014. Mortality data were available for a subset of 7,016 patients. Prescriptions for benzodiazepines, z-drugs (zaleplon, zolpidem, and zopiclone), and gabapentinoids were assessed.

The researchers reported 657 deaths and 29,540 OAT episodes, of which 42 percent involved benzodiazepine coprescription and 29 percent involved a concurrent prescription for z-drugs and for gabapentinoids.

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There was an increased duration of methadone treatment associated with concurrent prescription of benzodiazepines (adjusted mean duration of treatment episode, 466 days versus 286 days). There was also an association between benzodiazepine coprescription and an increased risk for DRP mortality (adjusted hazard ratio [HR], 2.96; 95 percent confidence interval [CI], 1.97 to 4.43; P < 0.001), with evidence of a dose-response effect. Similarly, coprescription of z-drugs showed evidence of an association with an increased risk for DRP mortality (adjusted HR, 2.75; 95 percent CI, 1.57 to 4.83; P < 0.001). Gabapentinoid coprescription was not associated with DRP mortality (HR, 1.54; 95 percent CI, 0.60 to 3.98; P = 0.373), but it was associated with increased mortality not attributed to DRP (HR, 1.83; 95 percent CI, 1.28 to 2.62; P = 0.001). When adjusting for duration of OAT, concurrent benzodiazepine prescription also increased mortality risk (adjusted HR for DRP with benzodiazepine concurrent prescription, 3.34; 95 percent CI, 2.14 to 5.20; P < 0.001).


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“Clinicians should be cautious about prescribing benzodiazepines to opioid-dependent individuals,” the authors write.

Several authors disclosed financial ties to the pharmaceutical industry.

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