Poisoning Deaths Associated With Buprenorphine Almost Always Involve Sedatives or Other Opioids

Buprenorphine has a favorable safety profile because of its partial agonist and ceiling respiratory depression effects. However, there are poisoning deaths associated with it. Researchers used data from autopsies of sudden and unexpected deaths in Finland, which has high rates of illicit buprenorphine use, to investigate the extent to which these deaths were associated with the use of other substances. In Finland, all sudden and unexpected deaths (12% of all deaths in this study period) are investigated with autopsy, including comprehensive toxicology in 75%.

• Between 2016 and 2019, there were 792 deaths at age 15–64 years where buprenorphine or norbuprenorphine were detected in post-mortem investigations. Of these deaths, buprenorphine was implicated in 271 (34%), buprenorphine with other opioids were implicated in 99 (13%), and buprenorphine was found but not implicated in 86 (11%). In the remaining 336 cases (42%), buprenorphine was detected, but the cause of death was not poisoning.
• Among the 271 deaths where buprenorphine was implicated, concomitant benzodiazepines were found in 94%, gabapentinoids in 50%, alcohol in 41%, and antipsychotics in 28%. There were only 3 cases (1%) where alcohol, benzodiazepines, or gabapentinoids were not also present.

Comments: This study affirms the safety of buprenorphine in comparison with other opioids. While the use of sedatives should not be a reason to deny someone access to buprenorphine to treat opioid use disorder, we should counsel patients on the dangers of concomitant use of benzodiazepines, gabapentinoids, and alcohol. In addition, concomitant prescribing of sedating medications should be carefully considered, particularly in combination.

Darius A. Rastegar, MD

Reference: Mariottini C, Kriikku P, Ojanperä I. Concomitant drugs with buprenorphine user deaths. Drug Alcohol Depend. 2021;218:108345.