Low-dose versus high-dose methadone for the management of neonatal abstinence syndrome

The primary objective was to compare median time to symptom relief (time from methadone initiation until two consecutive modified Finnegan [neonatal abstinence syndrome, NAS] scores < 8) between neonates receiving low-dose (≤0.275 mg/kg/day) versus high-dose (>0.275 mg/kg/day) methadone. Secondary objectives included assessment of factors associated with symptom relief.

Retrospective cross-sectional study.

Ninety-nine bed neonatal intensive care unit within a tertiary-care academic hospital.

Seventy-two neonates who received methadone for NAS over a 7.5-year period.

Kaplan-Meier curves with a log-rank test and a stepwise Cox proportional-hazard model were used to analyze outcomes.

The median dose for the low-dose (n = 40) and high-dose (n = 32) groups were 0.19 mg/kg/day (interquartile range [IQR], 0.12-0.24) divided every 6-12 hours and 0.4 mg/kg/day (0.3-0.44) divided every 6-8 hours, respectively. The median time to symptom relief was higher in the low-dose versus high-dose groups, 9.3 (5.8-24.6) versus 6.0 (5.4-12.5) hours, respectively (p = 0.014). Low-dose males had a longer time to symptom resolution than other groups (p = 0.008). Female premature neonates (<37 weeks gestation) had a shorter time to symptom relief than term neonates [adjusted hazard ratio = 2.96 (1.02-8.62)]. The median total duration of methadone was shorter but not statistically significant between high- versus low-dose groups, 17.5 (IQR: 11.0-25.0) versus 21.0 days (IQR: 10.0-28.0), respectively (p = 0.483).

Neonates receiving high-dose methadone had a significantly shorter time to symptom relief. Differences in sex were noted in response to therapy with low-dose males having a longer time to symptom relief and premature neonates a shorter time to symptom relief.