Clonidine monotherapy is as effective as morphine in treating neonatal opioid withdrawal, study finds

Pediatric researchers at the University of Kentucky have found that clonidine, an antihypertensive drug typically used to treat high blood pressure, may be as effective as morphine in treating neonatal opioid withdrawal syndrome (NOWS).

Clonidine has previously been used with morphine to reduce the symptoms of NOWS. The Kentucky research team investigated the potential of clonidine alone as an alternative to opioid-based treatments, which are commonly used for NOWS but pose risks related to prolonged opioid exposure in newborns.

In a study titled “Clonidine monotherapy for neonatal opioid withdrawal syndrome: a randomized trial,” published in Pediatrics120 infants exposed to opioids in utero were randomly assigned to receive either clonidine or morphine, with doses adjusted based on the severity of withdrawal symptoms.

Both groups had a median treatment duration of approximately two weeks, with 17 days for clonidine and 15 days for morphine, showing no significant difference in treatment duration.

A higher proportion of infants in the clonidine group (45%) required adjunctive therapy, compared with only 10% in the morphine group. Adjunctive therapy consisted of the administration of additional medications to infants who did not respond adequately to primary treatment with clonidine or morphine to manage NOWS.

If the initial medication did not control the infant’s withdrawal symptoms, the dose was increased gradually. If no improvement was seen after several dose increases, a secondary medication, usually phenobarbital, was introduced to help manage withdrawal symptoms alongside the primary treatment.

Statistical analysis showed that infants treated with clonidine were significantly more likely to require additional medications. The researchers attribute this to the fact that clonidine has a delayed onset of action, leading to dose increases and an increased need for adjunctive therapy under the trial conditions.

Initially, infants treated with clonidine showed poorer performance in specific areas, including arousal and signs of stress.

Neurobehavioral results revealed no significant differences between groups at the end of treatment, indicating that the delay in action of clonidine did not result in long-term differences in outcomes. Clonidine and morphine were well tolerated, with no significant adverse effects reported during the trial.

Although clonidine appears to be a viable non-opioid treatment for NOWS, the study authors suggest further research to optimize dosing strategies. Increasing the initial dose of clonidine or adjusting the treatment schedule could reduce the need for adjunctive treatments and shorten the time to symptom control.

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