Morphine versus clonidine for neonatal abstinence syndrome

Pediatrics. 2015 Feb;135(2):e383-91. doi: 10.1542/peds.2014-2377.


Objective: The study goal was to determine whether clonidine treatment of neonatal abstinence syndrome (NAS) would result in a better neurobehavioral performance compared with morphine.

Methods: This pilot study prospectively enrolled infants ≥ 35 weeks' gestational age admitted for treatment of NAS. After informed consent was obtained, infants were randomized to receive morphine (0.4 mg/kg per day) or clonidine (5 μg/kg per day) divided into 8 doses. A 25% dose escalation every 24 hours was possible per protocol (maximum of 1 mg/kg per day for morphine and 12 μg/kg per day for clonidine). After control of symptoms, the dose was tapered by 10% every other day. Clinical staff monitored infants by using Finnegan scoring. Masked research staff administered the NICU Network Neurobehavioral Scale (NNNS) at 1 week and at 2 to 4 weeks after initiation of treatment and the Bayley Scales III, and Preschool Language Scale IV, at 1-year adjusted age. Analyses included descriptive statistics, repeated measures analysis of variance, and Wilcoxon tests.

Results: Infants treated with morphine (n = 15) versus clonidine (n = 16) did not differ in birth weight or age at treatment. Treatment duration was significantly longer for morphine (median 39 days) than for clonidine (median 28 days; P = .02). NNNS summary scores improved significantly with clonidine but not with morphine. On subsequent assessment, those receiving clonidine had lower height of arousal and excitability (P < .05). One-year motor, cognitive, and language scores did not differ between groups.

Conclusions: Clonidine may be a favorable alternative to morphine as a single-drug therapy for NAS. A multicenter randomized trial is warranted.

Trial registration: NCT01734551.

Keywords: clonidine; morphine; neonatal abstinence syndrome; neurobehavioral manifestations; neurobehavioral scale; prenatal opiate exposure.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use*
  • Arousal / drug effects
  • Clonidine / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Morphine / therapeutic use*
  • Neonatal Abstinence Syndrome / rehabilitation*
  • Opioid-Related Disorders / rehabilitation*
  • Pilot Projects
  • Psychomotor Agitation / rehabilitation


  • Analgesics
  • Morphine
  • Clonidine

Associated data