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Buprenorphine Compared To Methadone

Buprenorphine compared to Methadone in Treating Opioid Use Disorder in Pregnancy

Shannon M. Colantuono

Methodist University Abstract

Objective: To determine if buprenorphine is superior to methadone in treating opioid use disorder during pregnancy. Methods: I used tertiary data from multiple journals using search engines to include Embase, PubMed and Google Scholar to compare studies and random control trials on fetal assessments of mothers with OUD taking methadone to those taking buprenorphine. Results:

Key Words: Opioid use disorder, pregnancy, buprenorphine, methadone. Introduction

According to the National Institute on Drug Abuse, roughly 2 million people in the United States suffered from prescription opioid use disorder (OUD) in 2014.1 Opioid use in the United States has resulted in an epidemic with roughly 60% of drug overdose deaths as a result of opioids with 14,000 deaths as a result in 2014 alone.2 In a study conducted on roughly one million women enrolled in Medicaid, approximately 20% of pregnant women filled a prescription for an opioid and of that 20%, 2% received a opioid prescription for greater than 30 days.3 Pregnant women with OUD require their addiction to be managed with the proper pharmacologic treatment that will cause the least amount of harm to the mother and unborn fetus. Babies born to women with an OUD are at increased risks for birth defects due to the mother’s daily life to include drug use, withdrawal, unhealthy lifestyle, and risks involved with intravenous drug use. 4 Neonatal complications include decreased fetal heart rate, premature birth, narcotic withdrawal, intrauterine growth restriction and even intrauterine demise. 4,5, 6 Neonatal abstinence syndrome (NAS) is a syndrome in which an infant goes through withdrawal from opioids shortly after birth and is often managed with morphine.7 NAS leads to longer hospital stays and higher medical bills for the infant and the mother.7 The ideal situation would involve the pregnant woman abstaining from the drug altogether during pregnancy but with the increased chance of relapse and the concurrent withdrawal, medical management is preferred.5 By managing OUD with medications such as methadone or buprenorphine, opioid levels are maintained in the mother to lower cravings for heroin or other opioids that could be detrimental to both the mother and fetus as well as encouraging prenatal care.5

Historically, methadone has been the standard of care in managing opioid addiction during pregnancy and has documented outcomes of the mother and fetus during its 40 years of use.8 Compared to the absence of medical management, methadone management resulted in better prenatal care and a better outcome for both the mother and infant.7 Methadone is a full μ-opioid receptor agonist with a high oral bioavailability that can only be prescribed by a physician.9 Buprenorphine (Subutex) is a semisynthetic opioid and partial agonist that was approved by the Food and Drug Administration in 2002 as an alternative to methadone to treat OUD.4,10 Due to buprenorphine only being a partial agonist, it may not be as effective in patients requiring higher doses but it is also less likely to result in overdose related deaths.9 Methadone management involves daily visits to a government-regulated clinic whereas physicians, nurse practitioners (NPs) or physician assistants (Pas) can prescribe buprenorphine with the proper certification.5,9

Pregnant women with OUD have multiple risk factors that increase their risk of adverse outcomes during their pregnancy. Opioid use during pregnancy is often associated with lower socioeconomic statuses, chaotic lifestyles, poor diet, and use of other drugs and alcohol.4 These same women are faced with stigmas that can result in them being less likely to seek prenatal care and making it more difficult to attend a clinic daily for methadone management.5, 10 Fear of criminal charges or threat of removal of children by child protective services is another barrier to prenatal care that pregnant women with OUD face.10 Opioid dependent mothers tend to have longer hospital stays, higher medical costs, and are at a much higher risk of death prior to discharge compared to women not using opioids.10

There is a need for patient centered care to manage opioid dependent women during pregnancy to include the obstetrician, counselor, case manager, and a clinician trained to aid in opioid replacement therapy.10 Opioid replacement therapy during the perinatal period has various risks to take into account and determining which medication to use can be difficult. To determine if buprenorphine is superior to methadone, my objective is to compare studies and random control trials on fetal assessments of mothers with OUD taking methadone to those taking buprenorphine to come to a conclusion.

Methods

For my topic I searched various databases to include PubMed, Embase and Google Scholar. I started by using key words such as “Opioid Use Disorder” and “Pregnancy” on my initial search. I further narrowed down my articles by searching using the keywords “Buprenorphine” and “Methadone”. For the purpose of this research, emphasis was placed on fetal assessment to include fetal heart rate, non-reactive stress test, fetal heart rate accelerations, as well as a biophysical profile score that were included in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study.8 This study was a double-blind, double-dummy, randomized clinical trial that included six U.S. sites and one European site and provided information collected on treatment of opioid use disorder in pregnancy.8Additional areas of focus include preterm birth, birth weight, head circumference, fetal/congenital anomalies, and spontaneous fetal death.5 This information was provided by a systematic review and meta-analysis that included data from articles written up to February 2015.5 Randomized control trials and observational cohort studies were compared to assess whether buprenorphine was safer than methadone in treating OUD in pregnancy.5

Fetal assessment

The Non-Stress Test (NST) is a non-invasive way to measure the fetal heart rate (FHR) over a thirty minute period to monitor for FHR accelerations.8 FHR accelerations would be defined as an sudden increase of 15 beats per minute (bpm) from baseline for a minimum of 15 seconds.8 A reactive NST is defined as two FHR accelerations over a twenty minute time period which is indicative of normal autonomic function, anything less than that would be considered nonreactive.8 The Biophysical profile (BPP) is also non-invasive and uses five parameters to predict fetal distress and/or abnormalities. The five parameters included in the BPP are: NST, fetal tone, fetal activity, fetal breathing movements and amniotic fluid index.8 Each parameter is given a score of either zero indicating abnormal or two being normal for a total ranging from 0-10.8

Results

MOTHER Trial

A total of 81 people were included in the data provided by the MOTHER trial with roughly 60% randomized to receive methadone treatment and the other 40% receiving buprenorphine treatment.8 There were minimal demographic differences between these two groups with all demographic characteristics having a p value greater than 0.05.8 Figure 1 provides a comparison of FHR pre and post dose assessments and shows that the buprenorphine treatment group had a lower mean FHR in comparison to the methadone group.8 Figure 2 illustrates that the fetuses exposed to buprenorphine had an increase in the amount of FHR accelerations compared to those exposed to methadone.8 Figure 3 shows an estimate for a non-reactive fetal NST in both treatment groups comparatively with less occurring in the methadone group.8 However there were limitations as a result of the fetuses in the methadone group being less likely to have a non-reactive NST prior to receiving the medication.8 The BPP scores are depicted in figure 4 showing that scores were higher in the buprenorphine treatment group, however the overall difference is insignificant.8

Systematic review and meta-analysis

In the systematic review and meta-analysis conducted by Zedler et al., they compared 3 randomized controlled trials, 12 prospective cohort studies and 3 retrospective cohort studies from various papers published from 2001-15.5 They compared the various articles to formulate figures 2 and 4 comparing the effects of buprenorphine and methadone on spontaneous fetal death rates, fetal/congenital anomalies, head circumference and birth weight.5 It is important to note that the size of the data markers correlate with study weight.

Discussion

References

1. Volkow, N. America’s Addiction to Opioids: Heroin and Prescription Drug Abuse. https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2016/americas-addiction-to-opioids-heroin-prescription-drug-abuse. Published May 14, 2014. Accessed July 8, 2017.

2. Opioid Overdose: Overview of an epidemic. https://www.cdc.gov/drugoverdose/data/index.html. Updated December 16, 2016. Accessed July 5, 2017.

3. Krans E, Patrick, S. Opioid use disorder in pregnancy: health policy and practice in the midst of an epidemic. Obstet Gynecol. 2016. 128(1): 4-10. doi:10.1097/AOG.0000000000001446.

4. Goodman, D. Buprenorphine for the treatment of perinatal opioid dependence: pharmacology and implications for antepartum, intrapartum, and postpartum care. J Midwifery Wom Heal. 2011. 56(3):222-229. doi:10.1111/j.1542-2011.2011.00049

5. Zedler B, Mann A, Kim M, et al. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Addiction. 2016. 111:2115-2128. doi:10.1111/add.13462.

6. Minozzi S, Amato L, Bellisario C, Ferri M, Davoli M. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database of Syst Rev. 2013. 12: 1-3. DOI: 10.1002/14651858.CD006318.pub3.

7. Dramatic Increases in Maternal Opioid Use and Neonatal Abstinence Syndrome. https://www.drugabuse.gov/related-topics/trends-statistics/infographics/dramatic-increases-in-maternal-opioid-use-neonatal-abstinence-syndrome. Updated September 2015. Accessed July 30, 2017.

8. Salisbury A, Coyle M, O’Grady K, et al. Fetal assessment before and after dosing with buprenorphine or methadone. Addiction. 2012. 107(1): 36-44. doi:10.1111/j.1360-0443.2012.04037.x.

9. Jones H, Heil S, Baewert A, et al. Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review. Addiction. 2012. 107(1) 5-27. doi:10.1111/j.1360-0443.2012.04035.x.

10. Roper V, Cox K. Opioid use disorder in pregnancy. J Midwifery Wom Heal. 2017. 00(0): 1-12. doi:10.1111/jmwh.12619.