Andjela Bäwert

Randomized controlled trials in pregnancy: scientific and ethical aspects. Exposure to different opioid medications during pregnancy in an intra-individual comparison.

BACKGROUND Chronic medical conditions such as opioid dependence require evidence-based treatment recommendations. However, pregnant women are under-represented in clinical trials. We describe the first within-subject comparison of maternal and neonatal outcomes for methadone- versus buprenorphine-exposed pregnancies. Although methadone is the established treatment of pregnant opioid-dependent women, recent investigations have shown a trend for a milder neonatal abstinence syndrome (NAS) under buprenorphine. However, it is not only the choice of maintenance medication that determines the occurrence of NAS; other factors such as maternal metabolism, illicit substance abuse and nicotine consumption also influence its severity and duration and represent confounding factors in the assessment of randomized clinical trials. CASE SERIES DESCRIPTION: Three women who were part of the European cohort of a randomized, double-blind multi-center trial with a contingency management tool [the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study], each had two consecutive pregnancies and were maintained on either methadone or buprenorphine for their first and then the respective opposite, still-blinded medication for their second pregnancy. Birth measurements, the total neonatal abstinence score, the total amounts of medication used to treat NAS and the days of NAS treatment duration were assessed. RESULTS Both medications were effective and safe in reducing illicit opioid relapse and avoiding preterm labor. Methadone maintenance yielded to a significantly higher neonatal birth weight. Data patterns suggest that buprenorphine exposure was associated with lower neonatal abstinence syndrome (NAS) scores. Findings from this unique case series are consistent with earlier reports using between-group analyses. CONCLUSIONS Buprenorphine has the potential to become an established treatment alternative to methadone for pregnant opioid-dependent women. Under special consideration of ethical boundaries, psychopharmacological treatment during pregnancy must be addressed as an integral part of clinical research projects in order to optimize treatment for women and neonates.

Peripartum pain management in opioid dependent women

Increased pain sensitivity and the development of opioid tolerance complicate the treatment of pain experiencedby opioid maintained pregnantwomenduring delivery and the perinatal period. Theaim of the present study was to investigate differences in pain management of opioid maintained compared to nondependent pregnant women during delivery and the postpartum period. 40 deliveries of 37 opioid dependent women enrolled in a double‐blind, double‐dummy randomized controlled trial (RCT) examining the safety and efficacy of methadone (mean dose at the time of delivery = 63.89 mg) and buprenorphine (mean dose at the time of delivery = 14.05 mg) during pregnancy were analyzed and participants were matched to a non‐dependent comparison group of 80 pregnant women. Differences in pain management (opioid and non‐opioid analgesic medication) during delivery and perinatal period were analyzed. Following cesarean delivery opioid maintained women received significantly less opioid analgesics (day of delivery p = 0.038; day 1: p = 0.02), NSAIDs were administered more frequently to opioid dependent patients than to the comparison group during cesarean section and on the third day postpartum. Significantly higher nicotine consumption in the group of opioid dependentwomenhad a strong influence onthe retrieved results, and might be considered as an independent factor of altered pain experience. Differences in pain treatment became evident when comparing opioid maintained women to healthy controls. These differences might be based on psychosocial consequences of opioid addiction along with the lack of an interdisciplinary consensus on pain treatment protocols for opioid dependent patients.

Are male neonates more vulnerable to neonatal abstinence syndrome than female neonates

BACKGROUND Prior studies have shown an increased vulnerability among males to adverse outcomes during the postnatal period. Most children exposed to opioids and other medications in utero develop neonatal abstinence syndrome (NAS), yet individual predisposition for NAS is poorly understood. OBJECTIVE This investigation examined the role of neonatal sex in the postnatal period for neonates exposed to standardized opioid maintenance treatment in utero with a focus on NAS regarding severity, medication requirements, and duration. METHODS This was a secondary analysis of data collected in a prospective randomized, double-blind, double-dummy, multicenter trial (MOTHER study) that examined the comparative safety and efficacy of methadone and buprenorphine during pregnancy. A total of 131 neonates born to opioid-dependent women randomized at 6 US sites (n = 74) and 1 European site (n = 37) were analyzed. Sex-based differences in birth weight, length, head circumference, NAS duration, NAS severity, and treatment parameters of full-term neonates were assessed. RESULTS Males had a significantly higher birth weight (P = 0.027) and head circumference (P = 0.017) compared with females, with no significant sex difference in rates of preterm delivery. No significant sex-related differences were found for NAS development, severity, or duration, or medication administered, and there were no significant differences in concomitant drug consumption during pregnancy (P = 0.959). CONCLUSIONS This unique prospective study shows similar postnatal vulnerability for both sexes, suggesting that factors other than sex are the major determinants of clinically significant NAS. ClinicalTrials.gov identifier: NCT 00271219.

Substanzabhängigkeit vom Opioidtyp – Behandlung mit oralen retardierten Morphinen

Regarding the chronic relapsing nature of opioid dependence and the generally disappointing results of short term options like rapid dose-tapering or detoxification treatment, opioid maintenance therapy seems to be the most effective intervention for this population group. Regarding the fact that development in all fields of medicine took place during the last years, diversification of treatment regarding opioid dependence is also evident. As in most countries methadone has been the only first choice agonist for treatment of this condition for many years, today several other synthetic opioids are approved for treatment of opioid dependence. In Austria, for example, oral slow release morphine is used for opioid maintenance therapy since 1998 and buprenorphine, a partial opioid-agonist, was approved in 1999 for this diagnosis. Despite the fact that for this indication oral slow release morphine is only approved in few countries - because of the lack of multicenter studies dealing with this topic and regarding the increased danger of abusing this substance intravenously - this treatment option including concomitant psychosocial support has been established as a recommendable alternative solution to methadone or buprenorphine. It has to be highlighted that treatment with oral slow release morphine should be accurately prescribed by physicians and further evidence-based scientific research is needed.