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 > 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.

Trial registration: ClinicalTrials.gov NCT00510016.

Figure 1

Patient randomization. One patient received the initial 3 doses as clonidine instead of the study drug (placebo).

Figure 2

Kaplan-Meier curve showing the effect of clonidine on days of DTO treatment for infants with NAS (log-rank; P = .02). The graph also includes the total length of DTO treatment for infants who rebounded who were assigned to the clonidine group.

Figure 3

Effect of clonidine on the amount of DTO (mL/kg) needed to control symptoms of NAS (mean ± SEM) (P = .03, analysis of variance, Bonferroni multiple comparisons). Placebo group, dashed line with circles; clonidine group, straight line with squares.