For opioid-dependent women who are pregnant, buprenorphine appears to offer an effective, safe first-line alternative to methadone, according to a report in the Dec. 9 issue of the New England Journal of Medicine.

In a randomized clinical trial comparing pregnancy outcomes among women seeking treatment for opioid dependence, infants exposed in utero to buprenorphine developed significantly less severe neonatal abstinence syndrome than did infants exposed in utero to methadone, said Hendrée E. Jones, Ph.D., of the department of psychiatry and behavioral sciences and the department of obstetrics and gynecology at Johns Hopkins University, Baltimore, and her associates.

The study involved 175 women aged 18-41 years who were at 6-30 weeks’ gestation when they entered treatment for opioid dependence at eight sites in the United States, Austria, and Canada. Eighty-six were randomly assigned to receive oral buprenorphine and 89 to receive oral methadone in a double-blind fashion.

After delivery, their neonates were assessed for signs and symptoms of neonatal abstinence syndrome (NAS) twice a day for at least 10 days.

There were five primary neonatal outcomes. Three of these – percentage of neonates requiring NAS treatment, peak NAS scores, and head circumference – did not differ between the two study groups. However, two of the five primary outcomes – amount of morphine required to treat NAS and length of hospital stay – favored the infants in the buprenorphine group. On average, infants exposed to buprenorphine required 89% less morphine and spent 43% less time in the hospital (10 days vs. 17.5 days) than infants exposed to methadone.

“The benefits of buprenorphine in reducing the severity of NAS among neonates with this complication suggest that it should be considered a first-line treatment option in pregnancy,” Dr. Jones and her colleagues said (N. Engl. J. Med. 2010;363:2320-31).

Neonates of mothers who received buprenorphine also required a significantly shorter period of treatment for NAS (4.1 days) than did neonates of mothers who received methadone, who required 9.9 days of treatment for NAS, they reported.

There were no differences in any maternal outcomes between women who took buprenorphine and those who took methadone.

Despite the comparable or even superior efficacy and safety of buprenorphine, there was one important drawback with the therapy: Women were more likely to discontinue treatment for opioid dependency with buprenorphine (33%) than with methadone (18%). Most (71%) of the women in the buprenorphine group who discontinued treatment cited “dissatisfaction” with the drug as their reason, while only 13% of those in the methadone group did so.

The benefits of buprenorphine therapy “must be considered in light of the markedly different rates of attrition,” Dr. Jones and her associates said. Future research should focus on reducing this “dissatisfaction” as well as on identifying “subpopulations of pregnant patients who are more likely to have a response to one medication than to the other,” they added.

This study was funded by grants from the U.S. National Institute on Drug Abuse. Buprenorphine tablets and the associated placebo were supplied by Reckitt Benckiser. Dr. Jones had no financial conflicts to disclose. One of Dr. Jones’ associates reported ties to a number of drug companies, and others had or were seeking federal grants.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

根据12月9日出版的《新英格兰医学杂志》中的一篇报道，对于阿片类药物依赖的孕妇，丁丙诺啡似乎是替代美沙酮的一种安全有效的一线药物。 

为了比较孕妇使用丁丙诺啡与美沙酮治疗后的妊娠结局，美国巴尔的摩约翰霍普金斯大学妇产科学系以及精神病学和行为科学系的Hendrée E. Jones博士及其同事对寻求阿片类药物依赖治疗的孕妇进行了一项随机临床试验。

该试验纳入了175位分别在美国、奥地利和加拿大8个地点接受阿片类药物依赖治疗、年龄介于18~41岁的女性，这些受试者在开始治疗时的孕龄为6~30孕周。研究者采用双盲法将受试者随机分配至口服丁丙诺啡治疗组(n=86) 与口服美沙酮治疗组(n=89)。在受试者分娩后，针对新生儿戒断综合征(NAS)的症状和体征对新生儿进行评估，每天2次，持续至少10天。

结果显示，在本研究的5个主要新生儿结局中，有3个(需要接受NAS治疗的新生儿百分比、NAS评分峰值和头围)无组间差异，另2个(治疗NAS所需的吗啡量和住院时间)在丁丙诺啡治疗组中较优。与暴露于美沙酮的婴儿相比，暴露于丁丙诺啡者的吗啡需要量减少89%，住院时间缩短43%(10天 对 17.5天) 。另外，在宫内暴露于丁丙诺啡的婴儿发生NAS的严重程度显著低于在宫内暴露于美沙酮的婴儿。母亲接受丁丙诺啡治疗的新生儿所需的NAS治疗时间(4.1天)亦较母亲接受美沙酮治疗者(9.9天)缩短。任何母亲结局均无组间差异。 

试验表明，丁丙诺啡的疗效和安全性与美沙酮相当甚至优于美沙酮。不过，丁丙诺啡也有一个重要的弊端，即采用丁丙诺啡治疗阿片类药物依赖的女性停止治疗的几率(33%)高于采用美沙酮治疗者(18%)；丁丙诺啡治疗组中大多数停止治疗的女性(71%)对所使用的药物“不满意”，美沙酮治疗组仅有13%。因此在考虑丁丙诺啡治疗的收益时也需要考虑这一因素。 

本研究获得美国国家药物滥用研究所的资助。丁丙诺啡片和相关的安慰剂由利洁时公司提供。 

Jones博士无经济利益冲突的披露内容。其中一位同事与许多药物公司有业务往来，其他同事已获得或正在寻求联邦拨款资助。

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