Buprenorphine and Methadone Discontinuation During Pregnancy and the Postpartum Period: A Nationwide Cohort Study

Treatment of pregnant patients with opioid use disorder with methadone or buprenorphine is crucial for maternal and neonatal safety. While several clinical trials have demonstrated higher treatment discontinuation rates for buprenorphine compared with methadone outside of pregnancy, evidence during pregnancy and the postpartum period is limited. The authors compared treatment discontinuation between buprenorphine and methadone during pregnancy and over follow-up through 1 year postpartum. This was a cohort study, using nationwide Medicaid data, of pregnant patients who initiated methadone or transmucosal buprenorphine (with or without naloxone) for opioid use disorder during the first trimester. The primary outcome was treatment discontinuation, defined as a treatment gap ≥60 days; alternative definitions for discontinuation were explored in sensitivity analyses. Hazard ratios were estimated using Cox proportional hazards regression with propensity score overlap weighting to control for confounding. Subgroup analyses were conducted, stratified by buprenorphine alone versus the buprenorphine/naloxone combination, each compared to methadone. Overall, 696 pregnant patients were identified who initiated methadone treatment and 1,538 who initiated buprenorphine treatment in the first trimester. Compared to methadone initiators, buprenorphine initiators were more likely to discontinue treatment during pregnancy (32.8% for buprenorphine vs. 25.6% for methadone; weighted hazard ratio=1.41, 95% CI=1.15, 1.72) and through 1 year postpartum (58.8% vs. 49.0%; hazard ratio=1.37, 95% CI=1.19, 1.57). For patients initiating the buprenorphine/naloxone combination, the hazard ratio was 1.73 (95% CI=1.36, 2.19) during pregnancy and 1.56 (95% CI=1.30, 1.86) through 1 year postpartum. For patients initiating buprenorphine alone, the hazard ratios were 1.14 (95% CI=0.90, 1.46) and 1.23 (95% CI=1.04, 1.46), respectively. Varying the treatment gap used to define discontinuation in sensitivity analyses yielded consistent results. Pregnant patients initiating transmucosal buprenorphine during early pregnancy were more likely to discontinue treatment than those initiating methadone, but treatment discontinuation was high for both treatments. The study findings highlight the importance of identifying and addressing barriers to treatment retention among pregnant patients with opioid use disorder.