Comparison of Safety and Efficacy of Methadone vs Morphine for Treatment of Neonatal Abstinence Syndrome

Abstract

IMPORTANCE Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established. OBJECTIVE To compare the safety and efficacy of methadone and morphine in NAS. DESIGN, SETTING, AND PARTICIPANTS In this randomized, double-blind, intention-to-treat trial, term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy were eligible. A total of 117 infants were randomized to receive methadone or morphine from February 9, 2014, to March 6, 2017. Mothers who declined randomization could consent to data collection and standard institutional treatment. INTERVENTIONS Infants were assessed with the Finnegan Neonatal Abstinence Scoring System every 4 hours and treated with methadone or placebo every 4 hours or morphine every 4 hours. Infants with persistently elevated Finnegan scores received dose increases. Infants who exceeded a predetermined opioid dose received phenobarbital. Dose reductions occurred every 12 to 48 hours when signs of NAS were controlled with therapy, stopping at 20% of the original dose. MAIN OUTCOMES AND MEASURES The primary end point was length of hospital stay (LOS). The secondary end points were LOS attributable to NAS and length of drug treatment (LOT). RESULTS A total of 183 mothers consented to have their infants in the study; 117 infants required treatment. Because 1 parent withdrew consent, data were analyzed on 116 infants (mean [SD] gestational age, 39.1 [1.1] weeks; mean [SD] birth weight, 3157 [486] g; 58 [50%] male). Demographic variables and risk factors were similar except for more prenatal cigarette exposure in infants who received methadone. Adjusting for study site and maternal opioid type, methadone was associated with decreased mean number of days for LOS by 14%

Methadone versus morphine treatment outcomes in neonatal abstinence syndrome: A meta‐analysis

“…Thus, the authors recommended that the choice of medication can affect NAS treatment outcomes, which may have some specificity to the prenatal opioid exposure. The second RCT proposed that short‐term outcomes were better in methadone‐treated infants compared with morphine‐treated infants . In fact, the maternal opioids in this study were buprenorphine, methadone and opioids prescribed for chronic pain.…”

“…Of the 1020 published studies that were identified, 5 were finally included in this meta‐analysis (two RCTs and three retrospective cohort analyses). Full details of trial selection are presented in Figure .…”

“…In the included studies, two RCTs showed that outcomes were better in methadone‐treated patients compared with morphine‐treated patient . However, three retrospective cohort analyses led to contradictory conclusions .…”

“…In early 2005, researchers suggested that oral morphine preparation and methadone‐treated infants had similar lengths of hospital stay (LOS) . However, a recent randomised clinical trial (RCT) showed that short‐term outcomes were better in infants who received methadone than in morphine‐treated infants . The purpose of this meta‐analysis was to determine whether morphine has better outcomes for NAS treatment than methadone.…”

Endogenous opioid peptides and brain development: Endomorphin‐1 and Nociceptin play a sex‐specific role in the control of oligodendrocyte maturation and brain myelination

“…A main concern in this regard is the dramatic escalation in opioid use and abuse together with the resulting increase of babies exposed to opioids during pregnancy and the large percentage of these newborns that are also administered opioids for their treatment of neonatal abstinence syndrome (Stover & Davis, ). We have previously found that the timing of myelination in the rat brain is disturbed by in utero and postnatal exposure to buprenorphine (Sanchez, Bigbee, Fobbs, Robinson, & Sato‐Bigbee, ) and methadone (Vestal‐Laborde, Eschenroeder, Bigbee, Robinson, & Sato‐Bigbee, ), the two opioid analogs currently successfully used in the management of pregnant opioid addicts (Davis et al, ; Kraft et al, ). Our studies suggested a μ‐opioid receptor (MOR) dependent acceleration of myelination induced by therapeutic doses of methadone and buprenorphine.…”