What is the recommended treatment for neonatal abstinence syndrome (NAS)?

Treatment for Neonatal Abstinence Syndrome (NAS)

The recommended first-line treatment for neonatal abstinence syndrome is a combination of non-pharmacological supportive care measures, followed by opioid therapy (preferably methadone) when symptoms are not adequately controlled, with adjunctive medications like phenobarbital or clonidine added for severe or uncontrolled symptoms. 1

Assessment and Monitoring

• Use standardized assessment tools to objectively evaluate withdrawal severity:

  • Modified Finnegan Neonatal Abstinence Scoring System is the dominant tool used in the United States 2
  • Eat, Sleep, Console (ESC) approach has shown promise in reducing unnecessary opioid treatment 3

• Monitoring requirements:

  • Regular vital signs monitoring
  • Assessment of feeding adequacy and weight gain
  • NAS scoring before and after medication administration
  • Additional monitoring for specific medications:
    • Clonidine: blood pressure and heart rate
    • Phenobarbital: therapeutic drug monitoring 1

Non-Pharmacological Management (First-Line)

Non-pharmacological interventions should be initiated for all infants with NAS:

1. Environmental modifications:

   • Minimize environmental stimuli (light and sound)
   • Place infant in a dark, quiet environment 2, 1

2. Comfort measures:

   • Careful swaddling to avoid auto-stimulation
   • Respond early to infant signals
   • Adopt appropriate positioning and comforting techniques 2, 1

3. Feeding support:

   • Ensure sufficient caloric intake
   • Encourage breastfeeding when not contraindicated
   • Breastfeeding is associated with decreased severity and duration of NAS symptoms 1

Pharmacological Management

When non-pharmacological measures fail to control symptoms, pharmacological treatment should be initiated:

First-Line Pharmacological Treatment:

• Opioid therapy: 94% of UK and 83% of US clinicians use an opioid as first-line treatment 2

  • Methadone (preferred):

    • Dosing: 0.2-0.9 mg/kg/day PO divided every 6-12 hours
    • Advantages: Longer half-life, shorter length of treatment compared to morphine 1
    • Weaning: Decrease dose by 10% per day down to 10-20% of maximum dose 1

  • Morphine (alternative):

    • Dosing: 0.3-1.0 mg/kg/day PO divided every 3-4 hours
    • PRN dosing: 0.03-0.05 mg/kg/dose every 3-4 hours 1
    • Weaning: Decrease dose by 10% per day once symptoms are controlled 1

Adjunctive Pharmacological Treatment:

When monotherapy fails to control symptoms, add one of the following:

• Phenobarbital:

  • Loading dose: 10-20 mg/kg PO
  • Maintenance: 5-8 mg/kg/day in 1-2 divided doses
  • Weaning: Decrease dose by 20% every 3-7 days 1
  • Particularly effective for non-opioid withdrawal 1

• Clonidine:

  • Dosing: 1 mcg/kg PO every 4 hours
  • Advantages: No known risk for neurodevelopmental delays or infant sedation
  • Requires blood pressure and heart rate monitoring
  • Weaning: Gradually increase dosing interval (q4h → q8h → q12h → discontinue) 1
  • The combination of morphine and clonidine has been shown to reduce treatment duration and total morphine requirements 1

Hospitalization and Observation Period

• Minimum observation periods:
  • Short-acting opioid exposure: minimum 3 days
  • Long-acting opioid exposure (e.g., methadone): minimum 5-7 days 2, 1
  • Benzodiazepine withdrawal: 4-7 days
  • SSRI withdrawal: at least 2 weeks 1

Pitfalls to Avoid

1. Inadequate initial dosing of medications
2. Too rapid weaning of medications
3. Failure to recognize polysubstance exposure
4. Overlooking non-pharmacological interventions
5. Using diazepam (documented lack of efficacy and adverse effects on infant suck and swallow reflexes) 2
6. Using paregoric (contains toxic ingredients) 2
7. Relying solely on maternal history without proper assessment to exclude other causes 2

Long-term Follow-up

• Early outpatient follow-up after discharge
• Educate caregivers about potential late withdrawal signs
• Monitor growth and development
• Assess for long-term neurodevelopmental outcomes 1

Despite the significant burden of NAS on the healthcare system, there remains substantial variation in treatment approaches across hospitals 4. The development of standardized protocols based on the best available evidence is essential to optimize outcomes for infants with NAS.