Highlight
- Buprenorphine initiators during early pregnancy show significantly higher treatment discontinuation rates than those initiating methadone.
- Treatment discontinuation remains high for both buprenorphine and methadone through one year postpartum.
- The discontinuation risk is notably higher with buprenorphine/naloxone combination compared to buprenorphine alone.
- Findings underscore the urgent need to identify barriers to treatment retention among pregnant patients with opioid use disorder.
Study Background
Opioid use disorder (OUD) in pregnancy presents critical challenges due to associated risks for both the mother and neonate, including withdrawal symptoms, relapse, and adverse perinatal outcomes. Standard care involves opioid agonist treatments, primarily methadone and buprenorphine, to stabilize maternal opioid levels, reduce illicit opioid use, and improve pregnancy outcomes. While clinical trials outside pregnancy often show higher treatment discontinuation with buprenorphine, comparative data during pregnancy and postpartum are limited. This study addresses this gap by evaluating real-world treatment discontinuation in a large national Medicaid cohort of pregnant patients initiating these therapies in the first trimester.
Study Design
This retrospective cohort study analyzed nationwide Medicaid claims data to identify pregnant patients initiating methadone or transmucosal buprenorphine (with or without naloxone) for OUD during their first trimester. The cohort included 696 methadone initiators and 1,538 buprenorphine initiators. The primary endpoint was treatment discontinuation, operationalized as a treatment gap of 60 days or more. Sensitivity analyses evaluated alternative discontinuation definitions. The investigators used Cox proportional hazards regression with propensity score overlap weighting to adjust for confounding variables. Subgroup analyses further stratified results by buprenorphine alone versus the buprenorphine/naloxone combination relative to methadone.
Key Findings
The study found that buprenorphine initiators were significantly more likely to discontinue treatment during pregnancy (32.8%) compared with methadone initiators (25.6%), with an adjusted hazard ratio (HR) of 1.41 (95% confidence interval [CI], 1.15 to 1.72). Over follow-up through one year postpartum, discontinuation was also higher for buprenorphine than methadone (58.8% vs 49.0%; HR 1.37, 95% CI 1.19 to 1.57).
More detailed subgroup analyses highlighted that patients initiating the buprenorphine/naloxone combination had an even greater hazard of discontinuation during pregnancy (HR 1.73, 95% CI 1.36 to 2.19) and postpartum (HR 1.56, 95% CI 1.30 to 1.86), whereas those initiating buprenorphine alone had hazard ratios closer to null during pregnancy (HR 1.14, 95% CI 0.90 to 1.46) but slightly elevated postpartum (HR 1.23, 95% CI 1.04 to 1.46).
Sensitivity analyses varying treatment gap thresholds consistently supported these findings, reinforcing the robustness of the observed differences.
Expert Commentary
This study importantly confirms in a large, real-world US cohort that pregnant patients treated with transmucosal buprenorphine exhibit higher rates of early discontinuation as compared to those on methadone. The particularly elevated discontinuation with the buprenorphine/naloxone formulation raises questions about patient adherence, side-effect profiles, and potential barriers such as stigma or access challenges during pregnancy. Since discontinuing OUD treatment during pregnancy is associated with increased risk of maternal relapse and adverse neonatal outcomes, these findings emphasize the need for enhanced clinical strategies and supportive services tailored to pregnant populations.
Limitations include reliance on Medicaid claims data which may not capture medication adherence or all clinical covariates. Additionally, the observational design precludes definitive causality. Despite adjustments for confounding, residual bias may remain. Nevertheless, these data complement randomized controlled trials by reflecting routine clinical experience across a heterogenous, nationwide population.
Conclusion
In summary, this nationwide cohort study highlights that while retention on opioid agonist therapy during pregnancy and postpartum is challenging overall, buprenorphine (especially the combination with naloxone) is associated with significantly higher discontinuation rates than methadone. These results underscore a critical unmet need to identify and overcome barriers to sustained OUD treatment among pregnant patients. Optimizing retention in opioid agonist therapies remains essential for improving maternal and neonatal outcomes in this vulnerable population.
Funding and ClinicalTrials.gov
The study was supported by research grants as acknowledged in the published article. No clinical trial registration was applicable given the retrospective cohort design.
References
Grace Lin CW, Bateman BT, Straub L, Hernández-Díaz S, Vine SM, Jones HE, Connery HS, Davis JM, Gray KJ, Lester B, Suarez EA, Sujan AC, Terplan M, Huybrechts KF. Buprenorphine and Methadone Discontinuation During Pregnancy and the Postpartum Period: A Nationwide Cohort Study. Am J Psychiatry. 2025 Aug 27:appiajp20241127. doi: 10.1176/appi.ajp.20241127. Epub ahead of print. PMID: 40859701; PMCID: PMC12573272.