Therapeutic approaches for neonatal abstinence syndrome: a systematic review of randomized clinical trials

Neonatal abstinence syndrome (NAS) which is observed in 55-94% of the newborns from opioids-taking mothers produces deleterious neurological symptoms. Various pharmacological therapies have been investigated in neonates with NAS. This article reviews all studies on NAS treatment to analyze the duration of treatment, length of hospitalization and possible drug adverse effects. The search was limited to the randomized clinical trials which examined the treatments of neonates with NAS. Scientific databases including PubMed, Cochrane Library, ISI Web of Science, Embase and Scopus were systematically searched. Retrieved articles were reviewed by two researchers and evaluated using the JADAD scoring system. Finally, the treatment duration, hospitalization length and drug side-effects were extracted. Methadone, buprenorphine and clonidine were found more effective than morphine. Diluted tincture of opium (DTO) in combination with phenobarbital or clonidine was significantly more effective than DTO alone. Clonidine was a significantly better adjunctive therapy than phenobarbital in reducing morphine treatment days. No significant difference was observed between morphine and DTO effectiveness. Deciding the optimal regimen to manage symptomatic NAS, as a single or an adjunct therapy is not possible based on the literature, due to the low quality, small size and short-term treatment considered in the published studies. Graphical abstract Process of selecting trials included in the present systematic review.