Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome

Abstract

Background: Current pharmacologic treatment of the neonatal abstinence syndrome with morphine is associated with a lengthy duration of therapy and hospitalization. Buprenorphine may be more effective than morphine for this indication.

Methods: In this single-site, double-blind, double-dummy clinical trial, we randomly assigned 63 term infants (≥37 weeks of gestation) who had been exposed to opioids in utero and who had signs of the neonatal abstinence syndrome to receive either sublingual buprenorphine or oral morphine. Infants with symptoms that were not controlled with the maximum dose of opioid were treated with adjunctive phenobarbital. The primary end point was the duration of treatment for symptoms of neonatal opioid withdrawal. Secondary clinical end points were the length of hospital stay, the percentage of infants who required supplemental treatment with phenobarbital, and safety.

Results: The median duration of treatment was significantly shorter with buprenorphine than with morphine (15 days vs. 28 days), as was the median length of hospital stay (21 days vs. 33 days) (P<0.001 for both comparisons). Adjunctive phenobarbital was administered in 5 of 33 infants (15%) in the buprenorphine group and in 7 of 30 infants (23%) in the morphine group (P=0.36). Rates of adverse events were similar in the two groups.

Conclusions: Among infants with the neonatal abstinence syndrome, treatment with sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than treatment with oral morphine, with similar rates of adverse events. (Funded by the National Institute on Drug Abuse; BBORN ClinicalTrials.gov number, NCT01452789 .).

Figure 1

Enrollment and Outcomes.

Figure 2. Duration of Treatment and Length of Hospital Stay

The duration of treatment (Panel A) and length of hospital stay (Panel B) were shorter in the buprenorphine group than in the morphine group (P<0.001 for both comparisons). Randomization was stratified according to the type of intended feeding method (bottle-feeding or breast-feeding). The box-and-whisker plots represent medians (horizontal lines) and interquartile ranges (top and bottom of the boxes); the I bars represent the maximum or minimum value or 1.5 times the interquartile range. Outliers are indicated by circles.