Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial.
OBJECTIVE
To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome.


METHODS
Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation.


RESULTS
The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age.


CONCLUSIONS
In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.
Agthe
Alexander G
AG
Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Kim
George R
GR
Mathias
Kay B
KB
Hendrix
Craig W
CW
Chavez-Valdez
Raul
R
Jansson
Lauren
L
Lewis
Tamorah R
TR
Yaster
Myron
M
Gauda
Estelle B
EB
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D003932:Heroin / Q000009:adverse effects*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008691:Methadone / Q000009:adverse effects*; D009357:Neonatal Abstinence Syndrome / Q000188:drug therapy*; D009892:Opium / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D003932:Heroin; D009892:Opium; D003000:Clonidine; D008691:Methadone