Emerging therapies for the treatment of neonatal abstinence syndrome

To examine the evidence for emerging treatment options, buprenorphine or clonidine, as monotherapy for the treatment of neonatal abstinence syndrome (NAS) against standards of care, morphine or methadone.

A PubMed literature search from 1946 to 2019 was performed using the terms NAS, neonatal withdrawal, buprenorphine and NAS, clonidine and NAS, morphine and NAS, methadone and NAS, opioids and pregnancy, opioids and NAS, prenatal exposure and opioids.

Study evaluation was limited to English-language studies conducted in humans. Articles were eliminated if subjects did not have a formal diagnosis of NAS. Additionally, studies were eliminated if neonates received diluted tincture of opium. Additional references were identified from a manual citation review.

Eight articles were evaluated. Five articles compared buprenorphine to either morphine or methadone. Buprenorphine was found to decrease length of NAS treatment an average of 9.2 days and decrease hospital length of stay (LOS) an average of 8.2 days. Three articles evaluated the use of clonidine for NAS, two as an adjunct to morphine and one as monotherapy. Adjunctive clonidine plus morphine versus phenobarbital plus morphine both significantly reduced the total morphine treatment duration; however, patients remained on adjunctive phenobarbital significantly longer than clonidine. As monotherapy, clonidine was found to decrease NAS treatment an average of 11 days and decrease overall LOS an average of six days compared to morphine treatment.

Treatment with buprenorphine or clonidine has shown favorable effects by reducing length of NAS treatment and LOS. These emerging therapies may be as effective as morphine or methadone for NAS, in combination with nonpharmacologic strategies. Long-term follow-up is needed.