Objective: In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, 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 syndrome. The primary objective of this study was to demonstrate the feasibility and, to the extent possible in this size of study, the safety of sublingual buprenorphine in the treatment of neonatal abstinence syndrome. 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 receive sublingual buprenorphine 13.2 to 39.0 mug/kg per day administered in 3 divided doses and 13 to receive standard-of-care oral neonatal opium solution. Dose decisions were made by using a modified Finnegan scoring system.
Results: Sublingual buprenorphine was largely effective in controlling neonatal abstinence syndrome. 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 who received buprenorphine and 1 infant who received standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for those in the neonatal-opium-solution group was 32 compared with 22 days for the buprenorphine group. The mean length of stay for the neonatal-opium-solution group was 38 days compared with 27 days for those in 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 neonatal abstinence syndrome.