Diluted tincture of opium (DTO) and phenobarbital versus DTO alone for neonatal opiate withdrawal in term infants

J Pediatr. 2002 May;140(5):561-4. doi: 10.1067/mpd.2002.123099.


Objective: The purpose of this study was to test the hypothesis that treatment of neonatal opiate withdrawal (NOW) in the term infant with diluted tincture of opium (DTO) and phenobarbital was superior to treatment with DTO alone.

Study design: This was a partially randomized, controlled trial in which 20 term infants exposed to methadone and/or heroin in utero were studied. The severity of NOW was assessed by using the Finnegan scoring system. Infants were assigned to either DTO and placebo (n = 10) or DTO and phenobarbital (n = 10) when medication was required. The primary outcome variable was the duration of hospitalization. Severity of withdrawal and hospital cost were secondary outcome variables.

Results: There were no significant differences in the gestational age, growth variables, maternal methadone dose, or age at enrollment between the 2 groups. The duration of hospitalization was reduced by 48% (79-38 days) (P <.001) and hospital cost per patient reduced by $35,856 (P <.001) for the DTO and phenobarbital group. Furthermore, these infants spent less time with severe withdrawal (P <.04), more time with mild withdrawal (P <.03), and required a lower maximum daily DTO dose (P <.009) when compared with the DTO-only group. The average duration of outpatient phenobarbital use was 3.5 months.

Conclusions: The combined use of DTO and phenobarbital resulted in a shorter duration of hospitalization, less severe withdrawal, and reduced hospital cost. This combination may be a preferred regimen for the treatment of NOW.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Drug Therapy, Combination
  • Heroin / adverse effects*
  • Hospital Costs
  • Humans
  • Hypnotics and Sedatives / therapeutic use*
  • Infant, Newborn
  • Length of Stay
  • Methadone / adverse effects*
  • Neonatal Abstinence Syndrome / drug therapy*
  • Neonatal Abstinence Syndrome / economics
  • Opium / therapeutic use*
  • Phenobarbital / therapeutic use*
  • Statistics, Nonparametric


  • Analgesics, Opioid
  • Hypnotics and Sedatives
  • Heroin
  • Opium
  • Methadone
  • Phenobarbital