Clonidine may be considered as a second line/adjunctive therapy for neonatal abstinence syndrome (NAS). Studies are ongoing on the use of clonidine as a first-line agent.
Why we are recommending this best practice
Phenobarbital is a nonselective central nervous system depressant that is sometimes used in combination therapy for NAS. It has been recommended mainly for non-opioid withdrawal in polysubstance exposure as an adjunct therapy. Its role is limited in opioid withdrawal given several disadvantages, such as lack of relief of gastrointestinal symptoms, impaired bonding and feeding in infants due to central nervous system depression, and potentially more long-term neurodevelopmental effects. Clonidine is an alpha-2 adrenergic receptor agonist that inhibits central nervous system sympathetic outflow and reduces norepinephrine levels. It reduces the autonomic symptoms (mediated in the locus coeruleus) of NAS. Clonidine has at least one high quality RCT supporting its use as an adjunctive agent to reduce length of pharmacotherapy treatment for NAS.
Strategies for implementation
- Develop unit-specific guidelines for initiation of clonidine as adjunct therapy if NAS is not adequately controlled with first-line therapy alone.
- Establish guidelines for escalation of clonidine.
- When weaning clonidine, consider a two-step reduction of the clonidine dose over 48 hours or weaning of opioids before stopping clonidine. This may reduce rebound NAS withdrawal symptoms.
- Clonidine has the potential to cause heart rate or blood pressure changes and monitoring is recommended. Monitor heart rate and blood pressure more closely during the first two days of clonidine therapy and for 48 hours after discontinuation.
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