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Updated: Dec 21, 2025

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Clonidine versus phenobarbital as adjunctive therapy for neonatal abstinence syndrome
Carrie Brusseau1, Tara Burnette2, R Eric Heidel3
1Department of Pharmacy, University of Tennessee Medical Center, Knoxville, TN, USA. cbrussea@utmck.edu.
Objective:
To compare clonidine versus phenobarbital as adjunctive therapy in infants who failed monotherapy with morphine for neonatal abstinence syndrome (NAS).
Study Design:
Prospective, randomized, open-label study of infants ≥ 35 weeks' gestation. Infants received clonidine or phenobarbital per protocol. Primary outcome was morphine treatment days. Secondary outcomes were inpatient adjunctive days, length of stay (LOS), triple therapy, safety, and readmission rates.
Results:
A total of 25 infants were treated with clonidine (n = 14) or phenobarbital (n = 11). Mean morphine treatment duration was significantly longer with clonidine (34.4 days, SD = 10.6) compared with phenobarbital (25.5 days, SD = 7.3, p = 0.026). The clonidine group also had higher inpatient adjunctive days (mean: 33.8 days [SD = 14.3] vs. 22 days [SD = 12.6], p = 0.042) and LOS (mean: 41.8 days [SD = 10.9] vs. 31 days [SD = 10]; p = 0.018) compared with phenobarbital.
Conclusions:
Phenobarbital, as adjunctive therapy, led to significantly shorter duration of morphine therapy, inpatient adjunctive days, and length of stay compared with clonidine.
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