Concomitant drugs with buprenorphine user deaths

Abstract

Background: Buprenorphine is abused in several countries notwithstanding its benefits as an analgesic and as an opioid agonist treatment medication. Benzodiazepines and alcohol have previously been associated with buprenorphine toxicity. This study elucidates the role of emerging concomitant drugs in different groups of buprenorphine user deaths. Methods: All cases in the Finnish national post-mortem toxicology database from 2016-2019 in which buprenorphine or norbuprenorphine was a laboratory finding in any post-mortem specimen and age at death of 15-64 years were investigated for cause and manner of death, concurrent drug and alcohol findings, age, and gender. Results: There were 792 deaths with a buprenorphine finding, of which buprenorphine was implicated in poisoning without other opioids in 271 cases (34 %). In this group of buprenorphine poisoning deaths, concomitant benzodiazepines were found in 94 % (clonazepam 53 %), illicit drugs in 63 %, gabapentinoids in 50 % (pregabalin 41 %), alcohol in 41 %, antidepressants in 32 %, and antipsychotics in 28 % of cases; only three deaths showed no benzodiazepines, alcohol, or gabapentinoids. Polydrug use was common regardless of the cause of death. In the age group 15 to 24 years, concomitant use of benzodiazepines and illicit drugs, and buprenorphine poisoning were more prevalent than in the age group 25-64 years. Conclusions: The unprecedentedly high concomitant use of benzodiazepines in buprenorphine user deaths obscures other possible pharmacological risk factors for buprenorphine poisoning that could be relevant for prevention. Higher mortality in the younger age group suggests particularly unsafe drug use patterns that should be addressed.

Changes in opioid-related deaths following increased access to opioid substitution treatment

“…The results show high concomitant use of primarily benzodiazepines in buprenorphine poisonings and indicate an increase in buprenorphinerelated deaths, especially among younger individuals. The study did not examine the proportion among the deceased who had prescriptions of buprenorphine or experience of OST [58]. The results of these, and other, studies illustrate a current increase in deaths related to OST-medications.…”

“…Only a few individuals had been prescribed methadone the year before the death, which indicates that the increasing trend was mainly a result of an increased exposure to non-prescribed methadone among younger opioid users [57]. Another recent study by Mariottini and colleagues [58] investigated buprenorphine-related deaths in Finland 2016-2019. The results show high concomitant use of primarily benzodiazepines in buprenorphine poisonings and indicate an increase in buprenorphinerelated deaths, especially among younger individuals.…”

Is Europe facing an opioid epidemic: What does European monitoring data tell us?

“…Opioids were the main cause of death but as well as heroin/ morphine, included methadone, buprenorphine and fentanyl analogues (Simonsen et al, 2020). Similarly, the analysis of a Finnish national post-mortem toxicology database showed that there were no death cases with buprenorphine as the only toxicological finding, with concomitant benzodiazepines commonly detected (Mariottini et al, 2020).…”

Determination of buprenorphine, norbuprenorphine, naloxone, and their glucuronides in urine by liquid chromatography–tandem mass spectrometry

“…A study of the relative safety of BUP and methadone for OAT revealed that BUP was six times safer than methadone regarding overdose risk in the general population 24 . Despite its relative safety, accidental and intentional BUP toxicity deaths still occur among both OAT patients and opioid users outside of treatment, with intravenous injection and concomitant sedative drug use being recognized as risk factors 25,26 . Even the combination product BUP/NAL is liable to misuse and fatal poisonings 27,28 …”

“…24 Despite its relative safety, accidental and intentional BUP toxicity deaths still occur among both OAT patients and opioid users outside of treatment, with intravenous injection and concomitant sedative drug use being recognized as risk factors. 25,26 Even the combination product BUP/NAL is liable to misuse and fatal poisonings. 27,28 Within therapeutic drug monitoring and toxicology, laboratory analysis of BUP and its metabolites is used to monitor adherence and to reveal BUP toxicity.…”