Can a pregnant woman be treated with methadone (opioid agonist)?

From the Guidelines

Yes, pregnant women with opioid use disorder can be treated with methadone, as it is considered a standard of care for managing opioid dependence during pregnancy. Methadone maintenance therapy helps prevent withdrawal symptoms that could harm the developing fetus. The typical starting dose is 20-30mg daily, which can be gradually increased based on the woman's symptoms to a maintenance dose, usually between 60-120mg daily 1. Treatment should continue throughout pregnancy and postpartum, with dosing adjustments as needed since pregnancy can alter methadone metabolism, sometimes requiring dose increases in the third trimester. Methadone should be administered under medical supervision at specialized clinics with prenatal care coordination. While neonatal abstinence syndrome (NAS) may occur in babies born to mothers on methadone, this is manageable and less dangerous than the risks of continued illicit opioid use or untreated withdrawal during pregnancy, which include preterm birth, fetal distress, and miscarriage 1. Comprehensive care should include counseling, social support services, and planning for potential NAS management after delivery.

Some key points to consider when treating pregnant women with methadone include:

• Methadone is a full mu-opioid receptor agonist, effective for treating perinatal opioid use disorder (OUD) 1.
• The goals of methadone therapy are to alleviate withdrawal symptoms and reduce cravings, with the aim of preventing illicit opioid use and its associated risks 1.
• Methadone dosing may need to be adjusted during pregnancy due to changes in methadone metabolism, and split doses or dosage increases may be necessary to prevent cravings and withdrawal symptoms 1.
• Comprehensive care for pregnant women with OUD should include screening for co-occurring substance use disorders, psychiatric illness, and infectious diseases, as well as counseling and social support services 1.
• Breastfeeding is recommended for women with OUD receiving methadone, as it can decrease the severity of NAS and reduce the need for treatment, but women should be informed about the potential risks and benefits 1.

Overall, methadone maintenance therapy is a crucial component of comprehensive care for pregnant women with opioid use disorder, and its use should be considered in the context of individualized, patient-centered care.

From the FDA Drug Label

Methadone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. However, an expert review of published data on experiences with methadone use during pregnancy by the Teratogen Information System (TERIS) concluded that maternal use of methadone during pregnancy as part of a supervised, therapeutic regimen is unlikely to pose a substantial teratogenic risk Pregnant women involved in methadone maintenance programs have been reported to have significantly improved prenatal care leading to significantly reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality

Methadone use in pregnant women is possible, but it should be used with caution. The potential benefits of methadone treatment must outweigh the potential risks to the fetus. Key points to consider:

• Methadone may not pose a substantial teratogenic risk when used as part of a supervised therapeutic regimen.
• Pregnant women in methadone maintenance programs have shown improved prenatal care and reduced incidence of obstetric and fetal complications.
• However, methadone exposure has been linked to decreased fetal growth, reduced birth weight, and mild but persistent deficits in performance on psychometric and behavioral tests in children.
• The decision to use methadone during pregnancy should be made on a case-by-case basis, considering the individual patient's needs and circumstances 2.

From the Research

Methadone Treatment for Pregnant Women

• Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy, as stated in a study published in The New England Journal of Medicine 3.
• However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization 3.
• Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence and has been shown to require significantly less morphine for NAS treatment, have a shorter hospital stay, and a shorter duration of treatment for NAS compared to methadone 3.

Pharmacological Treatment of Opioid Use Disorder in Pregnancy

• Methadone and buprenorphine are two types of opioid-agonist therapy that prevent withdrawal symptoms and control opioid cravings in pregnant women 4.
• The decision to use methadone vs buprenorphine for medication-assisted treatment (MAT) should be individualized based on local resources and patient-specific factors 4.
• National organizations continue to recommend MAT over opioid detoxification during pregnancy due to higher rates of relapse with detoxification 4.

Methadone Regulations and Pregnancy

• Methadone regulations have changed minimally since 1974, despite advances in the understanding of opioid use disorder (OUD) and the role of medications in its treatment 5.
• Current regulations can prevent optimal outcomes for pregnant women, including repeated episodes of maternal/fetal opioid withdrawal and other fetal physiologic abnormalities 5.
• A revised methadone system should provide treatment that is local, flexible, and limited in size to manage viral contagion risks, particularly for pregnant women 5.

Methadone and Neonatal Abstinence Syndrome

• The effect of methadone exposure during pregnancy on neonatal abstinence syndrome (NAS) is a complex and controversial topic, with a long history of studies and regulatory actions 6.
• A new laboratory measure, the serum methadone/metabolite ratio (MMR), has provided a tool for documenting the dynamic nature of perinatal metabolism and the need for dose adjustments and dose frequency changes 6.
• The concept of "fetal methadone dosing" emphasizes the importance of relative stability of methadone levels in the fetus for methadone dosing in pregnancy 6.

Methadone Dose Regimen and Neonatal Abstinence Syndrome

• A multiple daily dose methadone regimen in pregnancy may reduce the severity of neonatal abstinence syndrome (NAS) compared to a single daily dose regimen 7.
• A study found that increasing both methadone dose and dose frequency in response to maternal reports of withdrawal resulted in lower rates of NAS treatment and high rates of maternal recovery 7.
• The protocol was associated with low rates of treatment of NAS and high rates of maternal recovery, with cohort outcomes equaling or approximating US population norms 7.