Benzodiazepine, Z-drug up risk of poisoning in patients with opioid use disorder

Treatment with benzodiazepine or Z-drug appears to increase the risk of nonfatal drug-related poisoning in patients with opioid use disorder, according to a study. However, such risk is partially eased by use of buprenorphine.

The investigators performed a case-crossover study to examine prescription claims among persons aged 12–64 years with opioid use disorder who had buprenorphine prescriptions and had claims data in the IBM MarketScan databases (2006–2016), comprising 14,213,075 person-days of observation time for 23,036 individuals who experienced drug-related poisoning.

Exposures included buprenorphine and benzodiazepines or Z-drug prescriptions, standardized as daily diazepam-equivalent milligram doses and separated by pharmacologic properties (short- or long-acting benzodiazepines, Z-drugs). Variation in benzodiazepine or Z-drug and buprenorphine use between poisoning and nonpoisoning days was assessed using conditional logistic regression.

Buprenorphine treatment days correlated with a decrease in the risk of poisoning events (odds ratio [OR], 0.63, 95 percent confidence interval [CI], 0.60–0.66) compared with nontreatment days, while benzodiazepine or Z-drug treatment days correlated with an increase in the risk of such events (OR, 1.88, 95 percent CI, 1.78–1.98).

Stratified analyses by dose revealed a 78-percent (95 percent CI, 1.67–1.88) and 122-percent (95 percent CI, 2.03–2.43) increase in poisonings associated with low- and high-dose benzodiazepines or Z-drug treatment days, respectively.

High-dose, but not low-dose, benzodiazepine or Z-drug treatment resulted in higher poisonings in combination with buprenorphine cotreatment (OR, 1.64, 95 percent CI, 1.39–1.93). However, this was lower than that associated with benzodiazepine or Z-drug treatment without buprenorphine (low-dose: OR, 1.69, 95 percent CI, 1.60–1.79; high-dose: OR, 2.23, 95 percent CI, 2.04–2.45).

“Dose reduction of benzodiazepines or Z-drugs while maintaining buprenorphine treatment may provide the advantage of lowering drug-related poisoning risk,” the investigators said.