Methadone and buprenorphine for the management of opioid dependence in pregnancy.
ABSTRACT This article provides an overview and discussion of the collective maternal, fetal and neonatal outcome research on women maintained on methadone or buprenorphine during pregnancy. Its focus is on an assessment of the comparative effectiveness of methadone and buprenorphine pharmacotherapy, with particular attention given to recent findings from the literature. Recommendations for clinical practice are outlined, and directions for future research are presented. Findings from comparative studies of methadone and buprenorphine underscore the efficacy of both medications in preventing relapse to illicit opioid use in the treatment of opioid-dependent pregnant patients, as well as the simplicity of induction onto methadone and patient retention while receiving such therapy. Fetal monitoring suggests that buprenorphine results in less fetal cardiac and movement suppression than does methadone. The clinical implications of these findings need future exploration. For the neonate, evidence from studies using a wide range of designs, including retrospective chart reviews, prospective observational studies, and randomized clinical trials, show consistent results, with prenatal exposure to buprenorphine resulting in less severe neonatal abstinence syndrome relative to methadone. Any medication given to pregnant women should be prescribed only after considering the risk : benefit ratio for the maternal-fetal dyad. Medication choices for each opioid-dependent patient during pregnancy need to be made on a patient-by-patient basis, taking into consideration the patient's opioid dependence history, previous and current treatment experiences, medical circumstances and treatment preferences. Moreover, for a full remission of opioid addiction to be sustainable, both post-partum and across the lifespan, treatment providers must not rely solely on medication to treat their patients but should also utilize women-specific comprehensive treatment models that address the underlying multifaceted complexities of their patient's lives.
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ABSTRACT: Specialized prenatal care and substitution programs improve the perinatal prognoses of pregnant drug-abusers and their infants. Although methadone is well documented, little is known about high-dose buprenorphine (HDB). This prospective, multicenter (n = 35) observational study included 259 women on maintenance during pregnancy: 39% on methadone and 61% on HDB. Major findings were: 46% of them received good prenatal care; 62% had peridural analgesia; 12.3% delivered prematurely (<37 weeks); mean gestational age, 38.6 weeks; mean birth weight, 2822g. Three-quarters of the newborns developed neonatal abstinence syndrome (NAS) beginning at a mean age of 40h, with the mean maximum Lipsitz score of 9.1 at 72 h; half of them were treated, mainly with morphine hydrochloride. No baby died. Newborns were discharged with their mothers (96%) or placed in foster care (4%). Comparing methadone with HDB, respectively, mean age at the maximum Lipsitz score was 81 h versus 66 h (P = 0.066). The perinatal medical and social prognoses for these 259 drug addicts and their infants appeared to be improved by specialized prenatal care and was similar for methadone or BHD substitution during pregnancy.Drug and Alcohol Dependence 06/2006; 82(3):250-7. · 3.14 Impact Factor
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ABSTRACT: Buprenorphine is a mu-opioid receptor partial agonist and kappa-opioid receptor antagonist currently on trials for the management of pregnant opioid-dependent addicts. However, little is known about the effects of buprenorphine on brain development. Oligodendrocytes express opioid receptors in a developmentally regulated manner and thus, it is logical to hypothesize that perinatal exposure to buprenorphine could affect myelination. To investigate this possibility, pregnant rats were implanted with minipumps to deliver buprenorphine at 0.3 or 1 mg/kg/day. Analysis of their pups at different postnatal ages indicated that exposure to 0.3 mg/kg/day buprenorphine caused an accelerated and significant increase in the brain expression of all myelin basic protein (MBP) splicing isoforms. In contrast, treatment with the higher dose caused a developmental delay in MBP expression. Examination of corpus callosum at 26-days of age indicated that both buprenorphine doses cause a significant increase in the caliber of the myelinated axons. Surprisingly, these axons have a disproportionately thinner myelin sheath, suggesting alterations at the level of axon-glial interactions. Analysis of myelin associated glycoprotein (MAG) expression and glycosylation indicated that this molecule may play a crucial role in mediating these effects. Co-immunoprecipitation studies also suggested a mechanism involving a MAG-dependent activation of the Src-family tyrosine kinase Fyn. These results support the idea that opioid signaling plays an important role in regulating myelination in vivo and stress the need for further studies investigating potential effects of perinatal buprenorphine exposure on brain development.Glia 08/2008; 56(9):1017-27. · 5.07 Impact Factor
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ABSTRACT: Poor maternal and neonatal outcomes are associated with the pregnant heroin user. These include increased antepartum haemorrhage, decreased neonatal birthweight and increased neonatal mortality Medically supervised withdrawal from heroin during pregnancy has, however, been discouraged due to possible risk to the fetus and because of the high incidence of return to regular illicit heroin use by the mother. In recent years, however, a number of withdrawal procedures using anaesthesia, oral sedation, or intravenous sedation, precipitated by naloxone and/or naltrexone have been developed and carried out successfully on pregnant heroin users. We have now collated information on 18 cases (19 detoxifications) from three countries (Portugal, Australia and the United Kingdom). These case study data, although limited, indicate that detoxification of the pregnant heroin user is possible without significant risk to the neonate or mother, with many women not returning to dependent heroin use following detoxification. Naltrexone maintenance has also been used in the non-pregnant heroin user to discourage illicit heroin use. Similarly to methadone, stabilisation on naltrexone may be associated with conception and pregnancy Over the past three years, 26 women have conceived while on the Western Australia naltrexone program. Due to the unknown teratogenic effects, most have ceased naltrexone intake at approximately seven or eight weeks gestation. In a number of instances, however, naltrexone maintenance has been recommenced following return to a dependent pattern of heroin use. As a consequence, neonates have had different periods of naltrexone exposure, building from the initial seven or eight weeks. We now report on seven women who have delivered and three who are well into their third trimester. Neonatal and obstetric features were unremarkable with good Apgar scores, birthweight and head circumference observed. In the three cases still in third-term gestation, normal fetal development has been observed at recent ultrasound examinations. These case data indicate that naltrexone maintenance may have a role in the management of the pregnant heroin user.Australian and New Zealand Journal of Obstetrics and Gynaecology 12/2001; 41(4):424-8. · 1.30 Impact Factor