Morphine Versus Clonidine for Neonatal Abstinence Syndrome

Abstract

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 mg/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 mg/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. WHAT'S KNOWN ON THIS SUBJECT:Increased central adrenergic activity occurs with opiate withdrawal. Clonidine is an effective drug as an adjunct to morphine in the treatment of neonatal abstinence syndrome. It is unclear whether clonidine is effective as single-drug therapy.WHAT THIS STUDY ADDS: Clonidine, a a 2 -adrenergic agonist, seems to be as effective as morphine when used as a single-drug therapy for neonatal abstinence syndrome. Its administration results in improvement in neurobehavioral performance.

Laser Acupuncture for Neonatal Abstinence Syndrome: A Randomized Controlled Trial

“…10,11,12 Clinicians have treated NAS with a variety of opioid preparations. 49 In addition to opioid therapy, several other medications are in use as adjunctive therapy, such as clonidine and phenobarbital. 1,4,45 In a recent pilot study by Bada et al, 49 infants with NAS were treated with morphine (0.4 mg/kg per day) versus clonidine (5 mg/kg per day) divided into 8 doses.…”

“…49 In addition to opioid therapy, several other medications are in use as adjunctive therapy, such as clonidine and phenobarbital. 1,4,45 In a recent pilot study by Bada et al, 49 infants with NAS were treated with morphine (0.4 mg/kg per day) versus clonidine (5 mg/kg per day) divided into 8 doses. Treatment duration was significantly longer for the morphine group (n = 15; median 39 days) than for the clonidine group (n = 16; median 28 days) (P = .02), showing effects comparable to those of our pilot study (Table 2).…”

Advances in Pediatric Pharmacology, Therapeutics, and Toxicology

“…To determine whether single-agent clonidine treatment is as effective as morphine in the treatment of NAS, a pilot randomized double-blind single center study was conducted [93]. A total of 31 infants ≥35 weeks’ gestational age were enrolled in the study and randomized to receive morphine (0.4 mg/kg per day) or clonidine (5 ug/kg per day) divided into 8 doses.…”

“…Additionally, NNNS scores improved with clonidine but not morphine and one-year motor, cognitive, and language scores did not differ between the two groups. The investigators concluded that clonidine single agent therapy is as effective as morphine used for the treatment of NAS [93]. Since this was a small pilot study, a large randomized multicenter trial is necessary.…”

Validation of a HPLC/MS method for simultaneous quantification of clonidine, morphine and its metabolites in human plasma

“…Clonidine is an α 2 ‐adrenoceptor agonist commonly used as an antihypertensive agent (Nishina, Mikawa, Shiga, & Obara, ). In opioid withdrawal, enhanced noradrenergic activity is observed owing to the loss of opiate inhibition on noradrenergic neurons (Bada et al, ). Through stimulation of α 2 ‐adrenergic receptors, clonidine decreases noradrenergic neurotransmission and thus relieves withdrawal symptoms (Bada et al, ; Langer, Cavero, & Massingham, ; Nishina et al, ).…”