Davis JM, Shenberger J, Terrin N, et al. Comparison of Safety and Efficacy of Methadone vs Morphine for Treatment of Neonatal Abstinence Syndrome: a Randomized Clinical Trial. JAMA Pediatrics. 2018; DOI: 10.1001/jamapediatrics.2018.1307.
Neonatal abstinence syndrome (NAS) is a combination of signs of dysfunction in the central and autonomic nervous system of infants exposed to opioids in utero. There has been no universal standard for treatment. In this randomized, double-blind clinical trial 117 infants, from 8 US newborn units, born at full term with NAS (mothers had been prescribed opioids during pregnancy) were treated with either methadone or morphine. Methadone was associated with a reduction of 4 days in median length of stay in the hospital compared with morphine (16 vs. 20 days; p=.005).
Prior to this study, studies were mixed regarding the health and health care utilization outcomes for morphine vs. methadone for treatment of NAS. Clinical staff were blinded to the study drug (double-blind design), and the Finnegan Neonatal Abstinence Scoring System (FS) was used to assess severity of NAS. During dosing, if the infant with NAS continued to have FS scores of 8 or higher on 2 consecutive scores or 1 score of 12 or higher, then the dose of the study drug was increased to the next predetermined level. Phenobarbital was added if the study drug maximum dose was reached. Once control of NAS symptoms (i.e., opioid withdrawal) was achieved, then the study drug was decreased by 10% every 12 to 48 hours until treatment was stopped at 20% of the original dose. Unadjusted analyses found no statistically significant differences between the groups. However, when adjusting for clinical site and maternal opioid type, methadone was found to yield shorter length of stay (as above), related to shorter duration of treatment. Use of phenobarbital was slightly less common with methadone as well, but not to a statistically significant extent. The use of methadone in clinical care may also be favorable because it has a longer dosing interval than morphine (given every 8 hours vs every 4 hours).