Does Clonidine Reduce the Duration of Opioid Therapy for Neonatal Abstinence Syndrome?

Clonidine decreases the severity of opioid withdrawal in adults and older children, but its efficacy and safety in infants born to women with opioid dependence is not known. In this study, researchers randomized 80 infants with neonatal abstinence syndrome to standardized delivery of oral tincture of opium plus oral clonidine (1 µg/kg every 4 hours) or oral tincture of opium plus placebo. Ninety percent of infants in the clonidine group and 88% in the placebo group had intrauterine exposure to methadone, while 65% of infants in the clonidine group and 73% in the placebo group had intrauterine exposure to heroin. Therapy was guided by modified Finnegan scores.

• Median duration of therapy was 11 days in the clonidine group and 15 days in the placebo group (p=0.02).

• The mean dose of tincture of opium was 19.4 ml (7.7 mg morphine equivalents) in the clonidine group and 47.9 ml (19.2 mg morphine equivalents) in the placebo group (p=0.36).

• Seven infants in the clonidine group required restart of opium within 12–48 hours of stopping initial treatment compared with none in the placebo group.

• Blood pressure and heart rate were significantly lower in the clonidine group compared with the placebo group but remained within normal ranges.

• Three infants in the clonidine group died within 2 months of delivery. Each death occurred after discharge and was judged not to be due to clonidine.

Comments:

These findings suggest clonidine may be a potentially useful adjunct to tincture of opium in infants with neonatal abstinence syndrome. The “rebound” phenomenon observed in the clonidine group suggests that infants should be monitored carefully for at least 48 hours after discontinuation of therapy, and that, perhaps, only 1 drug at a time should be discontinued. The researchers are correct to point out that a larger study is needed to better assess short-term efficacy and long-term safety.

Kevin L. Kraemer, MD, MSc

Reference:

Agthe AG, Kim GR, Mathias KB, et al. Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial. Pediatrics. 2009;123(5):e849–e856.