Low-dose Buprenorphine Initiation in Pregnancy: A Systematic Review

Clinicians developed dosing strategies termed low-dose buprenorphine initiation (LDBI) to circumvent the prerequisite opioid withdrawal with traditional buprenorphine initiation. We aimed to determine the rates of withdrawal in patients who are pregnant transitioning from full opioid agonists to buprenorphine using LDBI.

We conducted a systematic review of the literature using Embase (including MEDLINE) and Scopus through February 5, 2025, augmented with searches in Google, Google Scholar, and www.clinialtrials.gov . Studies of any design were included if they evaluated LDBI in a patient who was pregnant; reports of traditional initiation were excluded. Studies were required to report the presence or absence of any withdrawal during initiation as an outcome. Investigators screened citations and articles for inclusion. Patient data were extracted using a standardized spreadsheet, and risk of bias was assessed using a tool by Murad et al. Data were synthesized with basic counts of variables and outcomes.

We included 7 studies, all observational, reporting 25 unique patients. Precipitated withdrawal was uncommon, occurring in 8% (n=2) of patients. Withdrawal of minimal, mild, or moderate severity was reported in 32% (n=8) of patients; however, this outcome was not consistently reported. Most studies did not describe selection methods or use validated tools to ascertain withdrawal.

Reports of LDBI in pregnant patients are emerging. While some level of withdrawal appears to be frequent, few studies reported precipitated withdrawal, and findings align with LDBI outcomes seen in nonpregnant patients. It is unknown how selection and/or reporting bias impact findings, and prospective, randomized, controlled trials are needed.