Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl

Objectives Buprenorphine can precipitate withdrawal in opioid-dependent persons with recent fentanyl use. However, the prevalence of this phenomenon is not clinically established. We sought to evaluate the incidence of buprenorphine-precipitated withdrawal in persons who use fentanyl. Methods We collected self-report data on opioid withdrawal symptoms after buprenorphine use, and, as a comparator, after methadone use, in 1679 individuals seeking treatment for opioid use disorder across 49 addiction treatment centers in the United States. Results The odds of developing severe withdrawal symptoms significantly increased when taking buprenorphine within 24 hours after fentanyl use (OR = 5.202, 95% CI = 1.979-13.675, P = 0.001), and within 24 to 48hours after fentanyl use (OR = 3.352, 95% CI =1.237-9.089, P = 0.017). As expected, patients did not report significantly higher rates of withdrawal when taking methadone after fentanyl use. Of those who waited less than 24hours after fentanyl before using buprenorphine or methadone, 22.19% (n = 152 of 685) and 11.56% (n = 23 of 199), respectively, reported severe opioid withdrawal. Conclusions This study supports previous anecdotal reports of buprenorphine-precipitated withdrawal from fentanyl. The odds of withdrawal symptoms significantly increased when taking buprenorphine after recent (within 48 hours) fentanyl use, however, this relationship was not observed in persons taking methadone, suggesting that this effect is specific to buprenorphine. Further research is urgently needed to describe the pharmacokinetics of non-medical fentanyl use to improve buprenorphine inductions strategies.