REVIEW OF: Winhusen TJ et al, JAMA Intern Med 2026;186(5):533–543
STUDY TYPE: RCT

Sublingual buprenorphine is standard for opioid use disorder (OUD) in pregnancy but has real drawbacks: daily peak-and-trough dosing, poor adherence, and diversion risk. Extended-release (XR) buprenorphine addresses all three, and now we have the first RCT to test it in pregnancy.

This unblinded trial enrolled 140 pregnant adults with OUD (6–30 weeks gestation) at 13 US sites, most of whom were already on sublingual buprenorphine. Participants were randomized to weekly subcutaneous XR (Brixadi) or sublingual buprenorphine and followed through pregnancy and 12 months postpartum. Monthly injections were avoided during pregnancy due to concerns about a non-active ingredient in that formulation. The primary outcome was illicit opioid abstinence based on weekly urine drug screens; missing samples were counted as positive.

During pregnancy, abstinence rates were higher in the XR group (82.5% vs 72.6%; p = 0.009). Postpartum, abstinence rates dropped and converged in both groups (~60% each). Neonatal opioid withdrawal syndrome outcomes were similar: About 30% of infants in each group needed opioid treatment, with no meaningful difference in duration. Infant birth head circumference was slightly larger in the XR group, but both averages fell within normal range.

Maternal safety favored XR: Serious adverse events were less common both during pregnancy (9% vs 27%) and postpartum (6% vs 19%). Fewer patients in the XR group needed opioid pain medication after delivery, and the XR group had slightly lower postpartum anxiety scores. Medication-related nonserious events were more common with XR (26% vs 7%), mostly mild-to-moderate GI issues.

CARLAT TAKE
This is the first RCT of XR buprenorphine in pregnancy, and the results are clinically useful. For pregnant patients with OUD, switching to weekly injections is a reasonable option, and this trial suggests they may do better. The main catch is the postpartum period, which is when things fall apart regardless of formulation, so that’s where the clinical focus needs to be. If a pregnant patient on sublingual buprenorphine is struggling with adherence or diversion concerns, switching to weekly XR is now backed by solid trial data.