Naltrexone Compared With Buprenorphine or Methadone in Pregnancy: A Systematic Review

Although naltrexone is an evidence-based medication for opioid use disorder (MOUD), few data are available with use in pregnancy. Our objective was to assess outcomes of pregnant individuals with opioid use disorder (OUD) taking naltrexone compared with those taking methadone or buprenorphine.

We undertook a systematic review using electronic database search (PubMed, CINAHL, EMBASE, PsycInfo), conference proceedings, and trial registries including ClinicalTrials.gov .

We conducted an electronic search of research articles through May 2023 for randomized controlled trials, prospective cohort, and retrospective cohort studies of naltrexone (oral, implant, or extended release) compared with methadone or buprenorphine (sublingual or extended release) among pregnant individuals with OUD. After double review of all articles, we abstracted obstetric (primary outcome: gestational age at delivery), neonatal (primary outcome: neonatal abstinence syndrome [NAS]), and substance use outcomes.

Five studies met eligibility criteria; four were retrospective cohort studies, and one was a prospective cohort study. Four studies included data on gestational age at delivery (weeks) with no difference detected between the two groups in any study (mean difference ranging -0.20, 95% CI, -1.49-1.09 to 0.8, 95% CI, -0.15 to 1.75). Three studies included data on NAS with all studies detecting a lower risk in the naltrexone group compared with methadone or buprenorphine (relative risk ranging from 0.08, 95% CI, 0.01-1.16 to 0.15, 95% CI, 0.06-0.36). Most studies (four of five) had a moderate or high potential for selection bias primarily driven by small sample size and lack of controlling for confounders.

Although the evidence base is limited, available data suggest that naltrexone use in pregnancy is a reasonable MOUD option with reassuring perinatal outcomes. To enhance confidence in this conclusion and to assess substance use outcomes, further comparative studies of pregnant people with OUD taking naltrexone and other MOUD types are needed.

PROSPERO, 42017074249.