Weekly buprenorphine injections beat daily pills for opioid abstinence during pregnancy

For a pregnant woman with opioid use disorder, the standard treatment - a daily dose of buprenorphine dissolved under the tongue - works reasonably well. But it has problems. Blood levels rise and fall with each dose, creating windows where cravings and withdrawal symptoms can break through. Adherence requires daily discipline. And the medication can be diverted or misused, a concern that complicates prescribing in populations already facing stigma.

An alternative exists: extended-release buprenorphine, delivered as a weekly injection under the skin, which maintains steady blood levels and eliminates daily dosing. It has already proven superior for opioid abstinence in non-pregnant adults. But until now, no completed randomized trial had tested it during pregnancy.

The PARADIGM trial

The study, called PARADIGM and published in JAMA Internal Medicine, randomized 140 pregnant adults to receive either weekly injectable extended-release buprenorphine or standard sublingual buprenorphine (with or without naloxone). The trial was supported by the National Institute on Drug Abuse through the NIH HEAL Initiative and conducted across multiple centers.

The primary finding: rates of illicit opioid abstinence during pregnancy, measured by urine drug screens, were significantly higher in the extended-release group. Postpartum, the extended-release formulation was non-inferior to sublingual treatment - meaning it performed at least as well, though the clear advantage seen during pregnancy narrowed after delivery. Participants who were no longer breastfeeding could transition to monthly injections during the postpartum period.

Safety findings

Serious maternal adverse events were less common in the extended-release group throughout the trial. Non-serious adverse events occurred at similar rates between groups during pregnancy, though they were more commonly judged to be medication-related in the extended-release arm. The neonatal outcomes that clinicians worry most about - specifically neonatal opioid withdrawal syndrome (NOWS) - did not differ between treatment groups.

NIDA director Nora Volkow described the results as clinically valuable, noting that the injectable formulation is safe for use in pregnancy and produces better abstinence outcomes - findings she called especially relevant during the ongoing opioid overdose crisis.

Why steady blood levels matter

The pharmacologic rationale is straightforward. Sublingual buprenorphine produces peak-trough fluctuations in blood levels with each daily dose. During the troughs, opioid receptors become less fully occupied, and cravings can intensify. For a patient whose daily life includes triggers, stressors, and potential access to illicit opioids, these vulnerability windows are dangerous.

Extended-release injections smooth out those fluctuations, maintaining more consistent receptor occupancy throughout the week. The result, as the trial data suggest, is better sustained abstinence. The weekly dosing schedule also removes the daily decision point that can undermine adherence.

Limitations to consider

The trial enrolled 140 participants, a modest sample that limits statistical power for subgroup analyses and rarer safety outcomes. The open-label extension phase, in which all participants received PrimeC, means the 12-month postpartum data lack a concurrent placebo comparison after the initial 6-month randomized period.

Lead author John Winhusen, a professor of psychiatry at the University of Cincinnati, noted that the results have immediate clinical application but also acknowledged that larger confirmatory studies would strengthen the evidence base. How the findings apply to patients with co-occurring psychiatric conditions, polysubstance use, or other complications is not addressed by this trial.

Access is also a practical concern. Extended-release buprenorphine requires a healthcare visit for each injection, which may be more challenging for patients in rural areas or those with limited transportation. The medication itself may be more expensive than generic sublingual formulations, though the cost comparison becomes more favorable when factoring in the value of better adherence and reduced relapse.

For clinicians managing opioid use disorder in pregnancy, the PARADIGM trial provides the first randomized evidence that weekly injections can safely and more effectively support treatment and recovery. Given the stakes - fatal overdose for the mother and withdrawal syndrome for the newborn - that evidence fills a significant gap.