To use or not to use buprenorphine for illegally manufactured fentanyl

This is the authors' abstract. We don't add key points for this paper.

The US opioid overdose crisis has been a triple wave phenomenon consisting of prescription opioids, heroin, and synthetic opioids. There is now a rising concern about a “fourth wave” driven by illegally manufactured fentanyl (IMF).1 Starting in 2013, IMF began gaining popularity in the United States, both in its pure form and mixed with heroin. Additionally, IMF is cheaper, and its cost continues to decline, with a concurrent rise in mortality from 2014 to the present day.1,3 This fourth wave recently hit a peak of more than 100,000 estimated drug overdose deaths in a 12-month period for the first time with over 64% of these deaths involving IMF. Fentanyl is 30–40 times more potent by weight than heroin and can induce severe physiologic dependence. The high potency of IMF can lead to rapid overdose, evidenced by 56% of the deceased being pulseless on arrival of first responders.4 IMF also presents special challenges to healthcare providers prescribing buprenorphine (BUP) treatment. In particular, BUP’s high binding affinity to the mu-opioid receptor (MOR) appears important in its relationship to fentanyl. BUP’s binding affinity to the MOR is 6.2 times greater than fentanyl. This means that BUP easily displaces fentanyl from the MOR, precipitating withdrawal in fentanyl-dependent individuals.2 This pharmacologic feature makes BUP induction particularly difficult in heavy fentanyl users. We must find ways to improve BUP induction in fentanyl users because medication-assisted treatment (e.g. BUP) is superior in improving outcomes, such as reduction in opioid use and overdoses relative to psychosocial strategies.5