Objective-In utero exposure to drugs of abuse can lead to the Neonatal Abstinence Syndrome (NAS), a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu opioid agonist used for treatment of adult detoxification and maintenance, but has never been administered to neonates with opioid abstinence. The primary objective of this study was to demonstrate the feasibility and to the extent possible in this sized study, the safety of sublingual buprenorphine in the treatment of NAS. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered.Methods-We conducted a randomized, open-label, active control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to sublingual buprenorphine 13.2-39 mcg/kg/day administered in three divided doses and thirteen to standard of care oral neonatal opium solution (NOS). Dose decisions were made using a modified Finnegan scoring system. Results-Sublingual buprenorphine was largely effective in controlling NAS. Greater than 98% of plasma concentrations ranged from undetectable to approximately 0.60 ng/ml, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants receiving buprenorphine and one infant receiving standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for the NOS group was 32 compared to 22 days for the buprenorphine group. The mean length of stay for the NOS group was 38 days compared to 27 days for the buprenorphine group. Treatment with buprenorphine was well tolerated.Conclusions-Buprenorphine administered via the sublingual route is feasible and apparently safe, and may represent a novel treatment for NAS.

AIMS-Over half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacologic therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS. DESIGN-Randomized PARTICIPANTS-Twenty-four term infants requiring pharmacological treatment for NAS.MEASUREMENTS-Outcomes were neonatal safety, length of treatment, and length of hospitalization.FINDINGS-Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (p=0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (p=0.05).CONCLUSIONS-Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine.