Treating Neonatal Abstinence Syndrome: Is Faster Better?

William T. Basco, Jr, MD, MS


August 30, 2017

Oral Morphine Versus Sublingual Buprenorphine for NAS

Although morphine is the drug almost exclusively used for neonatal abstinence syndrome (NAS), emerging data suggest that buprenorphine may be an acceptable and perhaps safer alternative. The two agents were compared in a recent single-site, double-blind, double-dummy clinical trial,[1] conducted from 2011 to 2016, in term neonates exposed to opioids during pregnancy.

The researchers used a validated scale to assign an NAS score to each newborn, and infants with scores above a predetermined cutoff level were placed on medical treatment. Infants were randomly assigned to receive either sublingual buprenorphine or placebo every 8 hours or oral morphine or placebo every 4 hours. Following usual protocols, doses of the active drugs or placebo were changed according to the infants' symptom scores.

The primary outcome of interest was the duration of treatment from the time the first drug was administered. Also evaluated were secondary and exploratory endpoints, such as length of hospital stay and infant physiologic symptoms.

Although the investigators hoped to randomly assign 80 infants, slow enrollment limited the sample to 63 infants (33 in the buprenorphine group and 30 in the morphine group). The median gestational age of the sample was almost 39 weeks, and the median birthweight was slightly more than 3 kg. Approximately one third of the infants were breast-fed. The sample was mostly white, with approximately 14% African-Americans. More than 90% of the mothers were on methadone, and 5% were on buprenorphine, for maintenance therapy. Two infants dropped out of the morphine group and three out of the buprenorphine group.

The median duration of treatment in the buprenorphine group (15 days) was shorter than in the morphine group (28 days), a difference of 13 days (95% confidence interval, -21 to -7 days). Similarly, the median length of hospital stay was much shorter among the children treated with buprenorphine (21 days) compared with those treated with morphine (33 days).

An additional secondary outcome was the use of supplemental phenobarbital. That, too, favored the buprenorphine group, 15% of whom required this therapy compared with 23% of those treated with morphine.

The adverse event rate was similar between the two groups. The respiratory rate was lower in the morphine-treated infants by an average of 4.4 breaths/min, and weight loss from birth was slightly lower among the infants treated with morphine. However, infant weight at days 14, 21, and beyond did not differ between the groups.

The authors conclude that buprenorphine was significantly more effective in this small trial of infants treated for NAS.


Any pediatric provider who spends any time in newborn nurseries these days can tell you how much of an issue NAS has become. I know that I have learned more about NAS in the past 2 years than I had learned in any of the previous 18 years of practice, because so many of these infants are transferred to floor status to complete their weaning and to decompress our nurseries. The prospect of being able to wean these infants in less time and just as safely is tremendous and, if implemented, would save considerable healthcare dollars in the United States.

With that in mind, I am hopeful that somewhere, someone is fast-tracking a multicenter trial that can enroll more infants to make sure that infrequent adverse effects (which are probably missed in a smaller trial, such as this one) don't pop up to dampen this enthusiasm.


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