Sublingual Buprenorphine for Treatment of Neonatal Abstinence Syndrome: A Randomized Trial

Abstract

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.

Neonatal Drug Withdrawal

“…A randomized comparison trial of sublingual buprenorphine versus neonatal opium solution for the treatment of NAS showed a nonsignificant reduction in length of treatment and duration of hospitalization in the buprenorphine group. 129 Buprenorphine therapy was well tolerated.…”

Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome

“…[1][2][3] Among infants exposed to chronic opiates in utero, the incidence of neonatal abstinence syndrome (NAS) ranges from 21 to 94%. [4][5][6] The onset, duration and severity of NAS may be impacted by the types and degree of fetal drug exposure and by neonatal treatment strategies, [7][8][9][10][11][12][13] use of tobacco during pregnancy, 14 gestational age 15,16 and use of maternal breast milk (MBM) as the primary source of nutrition. [17][18][19][20] The interactions of these factors and the composite impact on response to pharmacologic therapy for NAS have not been adequately elucidated in a large cohort of infants.…”

Neonatal Abstinence Syndrome Due to Opioid Abuse in Pregnancy

“…The treatment for morphine administration has been reported to last 8-79 days (13). This length of hospitalization interferes with maternal bonding, has potential for nosocomial infection, and is a major use of resources (14). Second-line therapy has been phenobarbital.…”