Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome
Introduction
Methadone is the only recommended pharmacotherapy in the United States for the treatment of opioid-dependent pregnant women (CSAT, 1993). Methadone given as part of comprehensive care during pregnancy is associated with positive maternal and infant outcomes (Kandall et al., 1976, Connaughton et al., 1977, Finnegan, 1991, Fischer, 2000, Lejeune et al., 2002). However, there is a neonatal abstinence syndrome (NAS) associated with methadone that often requires medical intervention. The NAS is a constellation of signs and symptoms indicating dysfunction of the autonomic nervous system, gastrointestinal tract, and respiratory system (Kaltenbach and Finnegan, 1990, Connaughton et al., 1975, Blinick et al., 1969).
Buprenorphine, a partial mu-opioid agonist recently approved for the treatment of non-pregnant opioid-dependent adults, may reduce the incidence and/or severity of NAS. In non-pregnant adults, little or no autonomic signs or symptoms of opioid withdrawal are observed following abrupt withdrawal from buprenorphine (Jasinski et al., 1978, Mello and Mendelson, 1980, Mello et al., 1982, Reisinger, 1995, Seow et al., 1986, Fudala et al., 1990). Likewise, prospective open-label controlled studies of neonates born to buprenorphine-treated mothers have found no to mild NAS, with only 17% of neonates requiring short-term treatment (Fischer et al., 2000, Johnson et al., 2001, Johnson et al., 2003). Because buprenorphine may be associated with a qualitatively and quantitatively different NAS from that observed with full mu-opioid agonists (Auriacombe et al., 1999), it may be more advantageous for the neonate than methadone. The primary hypothesis of this study is that antepartum treatment with buprenorphine will result in reduced NAS and length of hospitalization in the neonate relative to antepartum treatment with methadone.
This study was designed to compare the NAS in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. It was well-controlled, utilizing a randomized, double-blind, double-dummy design, and the primary focus was on several outcome variables hypothesized to be important in neonatal responsiveness to buprenorphine. However, the small sample size limited our ability to detect differences on these outcome measures at conventional levels of statistical significance. Nonetheless, this study provides valuable initial information about both the safety and efficacy of buprenorphine and methadone and their relative impacts on the neonatal abstinence syndrome and other important neonatal and maternal outcomes.
Section snippets
Participants
Participants were recruited from heroin-dependent patients admitted between May 2000 and March 2003, inclusive, to the residential unit of the Center for Addiction and Pregnancy (CAP), a multi-disciplinary treatment program (Jansson et al., 1996). The study was approved by the Johns Hopkins Bayview Medical Center Institutional Review Board. Participants provided written informed consent before participating.
Sampling
Inclusion criteria were: 21–40 years of age; estimated gestational age (EGA) by sonogram
Participant characteristics
Of the 30 randomized patients, 20 delivered while enrolled in the study; the remaining 10 dropped out during the study. Of those randomized to buprenorphine reasons for drop-out included discharged for medical condition (n = 1), missed consecutive dosing days (n = 4), and elected to withdraw (n = 1). Of those randomized to methadone reasons for discharge included, missed consecutive dosing days (n = 3) and elected to withdraw (n = 1). No significant demographic differences were observed between
Discussion
This is the first study to compare the effects of buprenorphine and methadone on the NAS under rigorous scientific conditions using randomized, double-blind, double-dummy methodology. Results of this study show no statistically significant differences between medication groups on the percentage of neonates treated for NAS, NAS peak score over all days or total number of morphine drops administered. There was a statistically significant difference between the two groups in the length of neonatal
Acknowledgements
We are indebted to the patients who participated in this study. We also thank Judy Jakubowski and Jenna Schulcz for the countless hours of hard work and dedication in seeing this study to completion. We also thank the following individuals and groups (listed alphabetically) for their assistance with this study: Gad Alpan; Behavioral Pharmacology Research Unit clinic, dispensary and pharmacy staff; Center for Addiction and Pregnancy staff; Robin Clay; Ed Cone; Data Safety Monitoring Board
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