High-dose Benzodiazepines Associated With Non-fatal Drug Poisonings in Patients Receiving Buprenorphine

Benzodiazepine use has been associated with both benefit and harm among patients receiving buprenorphine for opioid use disorder (OUD). Using a nationally representative database of commercially insured patients, this case-crossover study—in which cases acted as their own controls—examined the relationships between receipt of benzodiazepine and Z-drugs (i.e., zolpidem, zaleplon, and eszopiclone) and non-fatal drug-related poisonings among patients receiving buprenorphine for OUD.

• Among the 23,036 people with OUD who were receiving buprenorphine and had a non-fatal drug-related poisoning, 51% received a benzodiazepine and 22% received a Z-drug.
• Short-acting benzodiazepines had slightly higher odds of poisoning than long-acting benzodiazepines (odds ratios [ORs], 1.86 and 1.68, respectively).
• Receipt of high-dose benzodiazepines or Z-drugs (>30 mg daily diazepam-equivalents) was associated with an increased risk of poisoning (OR, 1.64), compared with receipt of low-dose benzodiazepines or Z-drugs (≤30 mg daily diazepam-equivalents).
• Days of benzodiazepine or Z-drug treatment without buprenorphine were associated with an increased risk of poisoning (OR, 1.81), while days of benzodiazepine or Z-drug treatment with buprenorphine treatment were associated with a decreased risk (OR, 0.63).

Comments: In this study of patients with OUD, receipt of high-dose benzodiazepines or Z-drugs was associated with increased risk of non-fatal drug poisonings. Although avoidance of prescribing high-dose benzodiazepines concurrently with buprenorphine may reduce the risk of poisoning in some patients, clinicians should still weigh the risks and benefits with patients before benzodiazepine dose reduction or discontinuation.

Tae Woo (Ted) Park, MD

Reference: Xu KY, Borodovsky JT, Presnall N, et al. Association between benzodiazepine or z-drug prescriptions and drug-related poisonings among patients receiving buprenorphine maintenance: a case-crossover analysis. Am J Psychiatry. 2021;178(7):651–659.