Sedatives for opiate withdrawal in newborn infants

Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Treatments used to ameliorate symptoms and reduce morbidity include opiates, sedatives and non-pharmacological treatments.

To assess the effectiveness and safety of using a sedative compared to a non-opiate control for NAS due to withdrawal from opiates, and to determine which type of sedative is most effective and safe.

This update included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2010), MEDLINE 1966 to April 2010 and abstracts of conference proceedings.

Trials enrolling infants with NAS born to mothers with an opiate dependence with > 80% follow-up and using random or quasi-random allocation to sedative or control. Control could include another sedative or non-pharmacological treatment.

Each author assessed study quality and extracted data independently.

Seven studies enrolling 385 patients were included. There were substantial methodological concerns for most studies including the use of quasi-random allocation methods and sizeable, largely unexplained differences in reported numbers allocated to each group.One study reported phenobarbitone compared to supportive care alone did not reduce treatment failure or time to regain birthweight, but resulted in a significant reduction in duration of supportive care (MD -162.1 min/day, 95% CI -249.2, -75.1). Comparing phenobarbitone to diazepam, meta-analysis of two studies found phenobarbitone resulted in a significant reduction in treatment failure (typical RR 0.39, 95% CI 0.24, 0.62). Comparing phenobarbitone with chlorpromazine, one study reported no significant difference in treatment failure.In infants treated with an opiate, one study reported addition of clonidine resulted in no significant difference in treatment failure, seizures or mortality. In infants treated with an opiate, one study reported addition of phenobarbitone significantly reduced the proportion of time infants had a high abstinence severity score, duration of hospitalisation and maximal daily dose of opiate.

Infants with NAS due to opiate withdrawal should receive initial treatment with an opiate. Where a sedative is used, phenobarbitone should be used in preference to diazepam. In infants treated with an opiate, the addition of phenobarbitone or clonidine may reduce withdrawal severity. Further studies are needed to determine the role of sedatives in infants with NAS due to opiate withdrawal and the safety and efficacy of adding phenobarbitone or clonidine in infants treated with an opiate for NAS.