Incidence of buprenorphine-precipitated opioid withdrawal in adults with opioid use disorder: A systematic review

Background and Aims: Buprenorphine is an evidence-based treatment for opioid use disorder, and the risk of precipitated withdrawal contributes to its underuse. The goal of this systematic review was to determine the incidence of buprenorphine-precipitated withdrawal in adults with opioid use disorder. Methods: This systematic review was registered on PROSPERO (CRD42023437634). We searched Medline, Embase Classic + Embase, and Cochrane CENTRAL from inception to 10 November 2023, and included original research that reported the incidence of sublingual buprenorphine-precipitated withdrawal in adults with opioid use disorder. Primary screening was completed by four independent reviewers. Full text review, data extraction and risk of bias assessments using the Newcastle Ottawa Scale and the Cochrane Risk of Bias 2 tool were completed by two independent reviewers. The primary outcome was precipitated withdrawal. Secondary outcomes were baseline opioids used, induction dose, initial Clinical Opiate Withdrawal Scale (COWS) score, location of induction, definition and severity of precipitated withdrawal and adverse events. The range of incidence of precipitated withdrawal across studies was described. Results: Our search yielded 10 197 unique citations. Twenty-one cohort and five randomized trials met inclusion criteria (n = 4497, range 20-1293). The overall incidence of precipitated withdrawal ranged from 0 to 13.2%. Nine studies defined precipitated withdrawal; definitions were inconsistent. Most patients used heroin at baseline. The most common initial dose of buprenorphine was between 2 mg and 8 mg (range: 0.075 mg-24 mg). Initial minimum COWS score ranged from 5 to 13. Induction locations included home, inpatient, emergency department, pre-hospital, outpatient and residential units. Of the fifteen studies with cases of precipitated withdrawal, nine studies did not report the severity of withdrawal experienced. Other induction-related adverse events varied. The overall quality of included studies was poor. Conclusions: The best available evidence suggests the incidence of buprenorphine-precipitated withdrawal in adults with opioid use disorder is low and should not be a barrier to use.