Update on Opioid Dependence in Pregnancy, by Medical Student T. J. Ridley

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This is an update on a previous post on treating opioid dependence in pregnancy, Treating Opioid-Dependent Pregnant Women: Is Society Ready for What Science Recommends? Can You Keep a Secret? – The Practical Psychosomaticist.

This is a presentation by a third-year medical student who was rotating through our Medical-Psychiatry Unit, Taylor J. Ridley, T.J. for short. We were wondering about the pros and cons of buprenorphine and methadone for maintenance opioid replacement since it’s recommended to offer women who are pregnant and opioid dependent in order to avoid the intermittent exposure of opioid withdrawal to the fetus, which can lead to a variety of complications, including fetal death. T.J. had a nice powerpoint presentation, and the bottom line that buprenorphine could be considered  first line choice for maintenance in pregnant women has to be tempered by a couple of caveats. There is a ceiling effect for buprenorphine and the dropout rate was higher than for methadone in the study by Jones and colleagues (NEJM), see reference below. Further, there are access barriers to buprenorphine that are at least as significant as those for methadone. Doctors are not eager to certify to dispense buprenorphine and there are few methadone maintenance clinics available.

Neonatal abstinence syndrome (NAS), which is essentially withdrawal suffered by the baby and can be marked by autonomic, neurologic, respiratory, and gastrointestinal symptoms that can require intensive care management, can occur with either methadone or buprenorphine.  However, there is consensus that there is much greater risk to both mother and fetus to simply trying to taper or detoxify pregnant women who are dependent on opioids.

Studies should continue on what’s the best drug and women should definitely have a say about which opioid they prefer. I think the saddest part of this story is the suffering that addiction causes. I can’t imagine how painful it is and I can’t imagine the guilt and loneliness. This is about so much more than the differences and similarities between buprenorphine and methadone. It’s about standing by each other.


Park, E. M., S. Meltzer-Brody, et al. (2012). “Evaluation and Management of Opioid Dependence in Pregnancy.” Psychosomatics 53(5): 424-432.

Background Opioid use disorders are a growing public health problem in the United States. Most women who are opioid-dependent are of childbearing age, and management of opioid dependence during pregnancy poses unique challenges. Assessment includes evaluation for addiction, withdrawal syndromes, and comorbid psychiatric diagnoses. Consultation-liaison (C-L) psychiatrists may also be involved in acute pain management, perinatal medication management, buprenorphine induction, and stabilization. For the past four decades, the standard of care has included methadone maintenance, but the increasing use of buprenorphine creates new treatment issues and opportunities. Objective To educate C-L psychiatrists in emergency and obstetrical settings about the appropriate approach toward the evaluation and basic management of women with opioid dependence in pregnancy. Method The authors reviewed the consensus literature and all new treatment options on opioid dependence during pregnancy. Discussion In this review, the authors summarize known and emerging management strategies for opioid dependence in pregnancy pertinent to C-L psychiatrists.

(2012). “ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy.” Obstetrics and gynecology 119(5): 1070-1076. Opioid use in pregnancy is not uncommon, and the use of illicit opioids during pregnancy is associated with an increased risk of adverse outcomes. The current standard of care for pregnant women with opioid dependence is referral for opioid-assisted therapy with methadone, but emerging evidence suggests that buprenorphine also should be considered. Medically supervised tapered doses of opioids during pregnancy often result in relapse to former use. Abrupt discontinuation of opioids in an opioid-dependent pregnant woman can result in preterm labor, fetal distress, or fetal demise. During the intrapartum and postpartum period, special considerations are needed for women who are opioid dependent to ensure appropriate pain management, to prevent postpartum relapse and a risk of overdose, and to ensure adequate contraception to prevent unintended pregnancies. Patient stabilization with opioid-assisted therapy is compatible with breastfeeding. Neonatal abstinence syndrome is an expected and treatable condition that follows prenatal exposure to opioid agonists.

Johnson, R. E., H. E. Jones, et al. (2003). “Use of buprenorphine in pregnancy: patient management and effects on the neonate.” Drug and alcohol dependence 70(2 Suppl): S87-101. It is estimated that 55-94% of infants born to opioid-dependent mothers in US will show signs of opioid withdrawal. Buprenorphine has been reported to produce little or no autonomic signs or symptoms of opioid withdrawal following abrupt termination in adults. To date, there have been 21 published reports representing approximately 15 evaluable cohorts of infants exposed to buprenorphine in utero. Of approximately 309 infants exposed, a neonatal abstinence syndrome (NAS) has been reported in 62% infants with 48% requiring treatment; apparently greater than 40% of these cases are confounded by illicit drug use. The NAS associated with buprenorphine generally appears within 12-48 h, peaks at approximately 72-96 h, and lasts for 120-168 h. These results appear similar to or less than that observed following in utero exposure to methadone. From a review of the literature, buprenorphine appears to be safe and effective in both mother and infant with an NAS that may differ from methadone both qualitatively and quantitatively.

Jones, H. E., K. Kaltenbach, et al. (2010). “Neonatal abstinence syndrome after methadone or buprenorphine exposure.” The New England journal of medicine 363(24): 2320-2331. BACKGROUND: Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. 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. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. METHODS: We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. RESULTS: Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events. CONCLUSIONS: These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).

McCarthy, J. J., M. H. Leamon, et al. (2005). “High-dose methadone maintenance in pregnancy: maternal and neonatal outcomes.” American journal of obstetrics and gynecology 193(3 Pt 1): 606-610. OBJECTIVE: This study assesses the effect of higher doses of methadone during pregnancy on maternal and fetal outcomes. STUDY DESIGN: We retrospectively reviewed clinical data for 81 mothers who received methadone and their 81 offspring. The cohort was divided into high-dose (>/=100 mg) and low-dose (<100 mg) groups. RESULTS: There were no differences in the rate of medication treatment for neonatal abstinence symptoms or days of infant hospitalization between the high-dose (mean, 132 mg) and low-dose (mean, 62 mg) groups. Despite longer histories of opiate abuse, the high-dose group had less illicit drug use at delivery. The whole cohort, which received an average of 101 mg/d, had an 81% rate of negative toxicology screens at delivery. CONCLUSION: High doses of methadone were not associated with increased risks of neonatal abstinence symptoms but had a positive effect on maternal drug abuse. Arbitrarily limiting methadone dose as a way of minimizing the risks of neonatal abstinence symptoms may be unwarranted.