Withdrawal during outpatient low dose buprenorphine initiation in people who use fentanyl: a retrospective cohort study

Harm Reduct J. 2024 Apr 9;21(1):80. doi: 10.1186/s12954-024-00998-9.


Background: Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients.

Methods: We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics.

Results: There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation.

Conclusions: Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients' withdrawal experiences.

Keywords: Buprenorphine; Fentanyl; Low dose buprenorphine initiation; Opioid agonist therapy; Opioid use disorder; Opioid withdrawal; Opioids; Precipitated withdrawal.

MeSH terms

  • Adult
  • Analgesics, Opioid / therapeutic use
  • Buprenorphine* / therapeutic use
  • Female
  • Fentanyl
  • Humans
  • Male
  • Opioid-Related Disorders* / complications
  • Opioid-Related Disorders* / drug therapy
  • Outpatients
  • Retrospective Studies
  • Substance Withdrawal Syndrome* / drug therapy


  • Buprenorphine
  • Fentanyl
  • Analgesics, Opioid