Abstract
Background and aims
There has been limited evidence synthesis examining the treatment of buprenorphine precipitated opioid withdrawal (BPOW). We aimed to conduct the first systematic review to assess the clinical utility of any pharmacological intervention in the management of BPOW.
Methods
Systematic review searching Medline, Embase, PsychINFO and CENTRAL from the date of database inception to 26 August 2025 for studies of any design reporting any pharmacological intervention in the management of BPOW compared with any or no other interventions, using adult participants aged 18 or over receiving buprenorphine and experiencing BPOW. We planned to combine outcomes using random-effects meta-analysis; where this was not possible results were reported narratively. We considered two outcomes and extracted (1) any reported measure or description of the change in opioid withdrawal symptoms (OWS) and (2) the number of individuals retained in buprenorphine treatment. Outcome quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
Results
Forty-three studies met inclusion criteria reporting on 137 participants. These comprised one pilot randomised controlled trial and 42 uncontrolled observational case series or case reports. Meta-analysis was not possible, and all evidence was of low or very low quality. The currently available randomised evidence suggests that use of intravenous magnesium sulphate, in addition to symptomatic treatment with clonidine, paracetamol and diazepam, may statistically significantly reduce OWS when compared with symptomatic treatment alone. The currently available observational evidence suggests that treatment strategies which include additional doses of transmucosal buprenorphine may demonstrate higher rates of symptom control and treatment retention than strategies which do not include additional doses of transmucosal buprenorphine.
Conclusions
There is a paucity of research into pharmacological management of buprenorphine precipitated opioid withdrawal. The limited very low to low quality evidence suggests treatment regimens that include magnesium sulphate and additional doses of transmucosal buprenorphine are potentially the most salient current options and avenues for future research in the management of buprenorphine precipitated opioid withdrawal.