Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized, Controlled Trial

Abstract

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 ≥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 μg/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.

Improving Care for Neonatal Abstinence Syndrome

“…2,6 Data suggest that hospitals vary in identification 8 and management 7,8 of infants with NAS. There have been several innovations over the last decade in the management of opioid-dependent mothers 13 and infants with NAS, 14,15 but it is unclear how broadly these innovations have been adopted. In 2012, the AAP issued a policy statement focused on management of substance-exposed infants.…”

Neonatal Drug Withdrawal

“…In a small case series, 6 of 7 infants with NAS showed significant resolution of signs when treated with oral clonidine. 132 In a randomized double-masked controlled trial, Agthe et al 133 compared the efficacy and safety of treating NAS with DTO plus oral clonidine (1 µg/kg every 3 hours) versus DTO plus placebo in 80 infants with prenatal exposure to methadone and/or heroin. The combination therapy significantly reduced the median length of treatment of all infants and for infants exposed to methadone, but more infants in the DTO/clonidine group required resumption of DTO after initial discontinuation.…”

Neonatal Abstinence Syndrome

“…153,154 Clonidine and phenobarbital levels can be monitored, and both are beneficial for decreasing the duration of treatment as well as for curtailing the use of higher doses of morphine or methadone. 138,155 …”