Split Dosing of Methadone During Pregnancy Improves Outcomes

Methadone has been shown to improve outcomes for pregnant persons with opioid use disorder (OUD) and their newborns. Physiologic changes during pregnancy alter the metabolism of methadone, so it is often split into two or three doses when administered to pregnant patients. Researchers conducted a systematic review of studies looking at split dosing of methadone during pregnancy to evaluate the impact on maternal, fetal, and neonatal outcomes.

• Eight studies were included in this analysis: one case study, three case series, three cohort studies, and one clinical trial.
• Two studies demonstrated increased methadone clearance and metabolism during pregnancy.
• Two studies looked at fetal measures with split dosing compared with single dosing and reported improved outcomes.
• Four studies looked at measures of maternal drug use with split dosing and reported improved outcomes.
• Four studies looked at neonatal outcomes and observed no increase in adverse outcomes with higher doses or split dosing.

Comments: This review shows that the evidence is sparse, but it supports the practice of split dosing of methadone during pregnancy among people with OUD.

Darius A. Rastegar, MD

Reference: Khan NZ, Hand DJ, Qian E, et al. Split-dosing of methadone during pregnancy and postpartum period: a systematic review of outcomes. J Addict Med. 2025 [Epub ahead of print]. doi:10.1097/ADM.0000000000001470.