Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl

Abstract

ObjectivesBuprenorphine 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.MethodsWe 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.ResultsThe 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.ConclusionsThis 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.

“Just give them a choice”: Patients' perspectives on starting medications for opioid use disorder in the ED

“…Participants noted an emerging issue with buprenorphine as the opioid supply is increasingly comprised of fentanyl rather than heroin—that people using fentanyl may have a higher risk of precipitated withdrawal despite a period of abstinence that was previously considered safe 39–42 . This is emerging in the literature as an important issue, as it makes both people with OUD and clinicians hesitant to initiate buprenorphine 39–42 .…”

“…Participants noted an emerging issue with buprenorphine as the opioid supply is increasingly comprised of fentanyl rather than heroin—that people using fentanyl may have a higher risk of precipitated withdrawal despite a period of abstinence that was previously considered safe 39–42 . This is emerging in the literature as an important issue, as it makes both people with OUD and clinicians hesitant to initiate buprenorphine 39–42 . Fortunately, research addressing the treatment of precipitated withdrawal is a rapidly evolving; “micro” and “macro” dosing of buprenorphine may be effective, and IV ketamine has also been used with good effect 43–47 .…”

“…39,40 Alternative dosing strategies (both quantity and timing) may be necessary for those using fentanyl. 41 Relapse is part of recovery. Every patient interaction is an opportunity to help someone restart their path to recovery.…”

“…safe. [39][40][41][42] This is emerging in the literature as an important issue, as it makes both people with OUD and clinicians hesitant to initiate buprenorphine. [39][40][41][42] Fortunately, research addressing the treatment of precipitated withdrawal is a rapidly evolving; "micro" and "macro" dosing of buprenorphine may be effective, and IV ketamine has also been used with good effect.…”

Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse

“…A long-acting injection of extended-release buprenorphine has been shown to be feasible for users of heroin-containing fentanyl in an open-label trial [ 94 ]. However, these pharmacotherapies are limited by high relapse rates, a high risk of precipitating withdrawal in individuals who are exposed to fentanyl, and weak efficacy in preventing fentanyl overdose [ 95 ]. Thus, new approaches and novel medications are still needed for the treatment of opioid use disorder.…”