From 1992 to 2012, the percentage of pregnant women seeking treatment for opioid use disorder
(OUD) rose from 2% to 28%. Similarly, from 1998 to 2011, the percentage of pregnant women with OUD rose 127%. OUD during pregnancy can cause fetal respiratory depression, intrauterine growth restriction, placental abruption, postpartum hemorrhage, fetal sedation, preterm labor, stillbirth, and intrauterine fetal death. Newborns can develop neonatal abstinence syndrome (NAS), characterized by withdrawal symptoms such as hyper-irritability, excessive crying, diarrhea, vomiting, and poor feeding. Mothers being treated for OUD may experience withdrawal symptoms such as shaking, body aches, nausea, vomiting, and higher BP levels, because their maintenance therapy dosages may be significantly lower than the level of opioids they were previously taking. This article reviews treatments for OUD and how to reduce the risks of therapy for neonates and mothers.
METHADONE: THE STANDARD Since its introduction in the 1960s, methadone has been widely used as maintenance therapy for OUD and is the standard of treatment in pregnancy. Methadone is an opioid agonist that reduces the symptoms of opioid withdrawal, reduces drug cravings, prevents NAS, and inhibits the ecstatic effect to reduce drug abuse. Benefits of methadone include its minimal euphoria and long half-life, which reduce drug-seeking behaviors. Methadone maintenance programs educate and support pregnant women, providing social support and monitoring drug administration. However, the drug has drawbacks: Because it is administered through structured programs, methadone treatment holds stigma, leading to less funding and community support. The clinic environment in which methadone is administered to patients of all stages of recovery together, and the tightly regulated, direct observation implemented can be viewed as punitive. Methadone also poses a high risk of sedation, relapse, and overdose. Because methadone is a major CYP3A4 substrate and norepinephrine re-uptake inhibitor, it interacts with serotonergic agents and other drugs such as phenytoin, ketoconazole, and clonidine. Preterm delivery is another concern, and elevated concentrations of the drug also are detected in breast milk, posing risk to the neonate.
A PROMISING ALTERNATIVE New clinical studies indicate that buprenorphine mono- therapy can be a promising alternative to methadone for treating OUD in pregnant women. A partial agonist at the mu receptors, buprenorphine contributes to less over- dose and misuse compared with methadone, which has full agonist activity at the mu receptors. In a study comparing methadone with buprenorphine in pregnant women with OUD, buprenorphine demonstrated superior outcomes over methadone in terms of the mother deliver- ing the child at term, fewer low-birthweight newborns, lower incidence of NAS, and mothers starting opioid agonist therapy earlier in the pregnancy. Buprenorphine also is known to cause less sedation and respiratory depression than methadone. It reduces relapse in pregnant women and only minimal quantities of buprenorphine enter the breast milk, making it a feasible alternative for women who decide to breastfeed. Although methadone requires inpatient monitoring of response to therapy, this may not always be convenient, making buprenorphine a more available option because it can be administered at home.
According to the American College of Obstetricians and Gynecologists (ACOG), treatment for OUD in pregnancy involves buprenorphine or methadone. ACOG states that methadone in addition to cognitive and behavioral therapy has been the standard of care for heroin dependence in pregnant women. However, ACOG indicates the increasing use of buprenorphine and its benefits such as fewer drug interactions, not requiring inpatient treatment nor as many dose adjustments during pregnancy. The recommended initial dose of buprenorphine for a pregnant woman with OUD is 2 to 4 mg sublingually daily, followed by an assessment of the patient’s symptoms. An additional 2 to 8 mg can be added to the daily dose if withdrawal symptoms persist. Most patients achieve a target dose of 16 mg/ day, but the optimal dose is determined based on regular assessment of the patient and her response to treatment. The 2020 American Society of Addiction Medicine (ASAM) practice guidelines recommend buprenorphine or methadone as the current standard of care for pregnant women with OUD but state the need for larger studies to assess the safety and efficacy of buprenorphine compared with methadone in pregnant women.
TREATMENT LIMITATIONS Despite the advantages of buprenorphine treatment, the drug has limitations. Patients must be in mild to moderate withdrawal to begin buprenorphine treatment because its goal is to alleviate withdrawal symptoms. Although dose increases throughout pregnancy may be necessary, persistent withdrawal symptoms mean that treatment is ineffective. Buprenorphine also has more risks of precipitated withdrawal due to its partial agonism, and no long-term studies have been done on its effect on infants and children. Although rare, liver dysfunction has been reported in fewer than 1% of patients. Because buprenorphine’s effects begin to plateau at higher doses, at low doses it can produce acute euphoric effects similar to a 60-mg dose of methadone. Thus, it carries an increased risk for unauthorized sale for patients who lack physical dependence.
CONCLUSION Women may be on buprenorphine maintenance therapy when they become pregnant, or a pregnant woman may be unable to take methadone, so clinicians should under- stand buprenorphine therapy and consider it for pregnant patients when appropriate. Although not yet considered the standard of care, buprenorphine is the only accessible option for treating OUD at home. Pain management for pregnant women with OUD is multifactorial and includes medication-assisted treatment and non- pharmacologic interventions. Clinicians who are aware of the advantages and disadvantages of treatments for OUD can help patients address this issue safely during pregnancy.