What are the American Academy of Sleep Medicine (AASM) guidelines for treating idiopathic hypersomnia (IH)?

AASM Guidelines for Idiopathic Hypersomnia Treatment

The American Academy of Sleep Medicine (AASM) strongly recommends modafinil as the first-line treatment for idiopathic hypersomnia (IH) in adults, with several conditional recommendations for alternative medications including clarithromycin, methylphenidate, pitolisant, and sodium oxybate. 1

First-Line Treatment

• Modafinil is the only medication with a strong recommendation (meaning clinicians should follow this under most circumstances) for treating idiopathic hypersomnia in adults 1
• Modafinil significantly improves self-reported sleepiness on the Epworth Sleepiness Scale by approximately 5 points compared to placebo, based on high-certainty evidence 2
• Modafinil also improves objective measures of wakefulness, with patients able to remain awake nearly 5 minutes longer on the Maintenance of Wakefulness Test compared to placebo 2

Conditional Recommendations

The AASM conditionally recommends the following medications (meaning clinicians should use clinical knowledge and consider individual patient values and preferences):

• Clarithromycin - suggested as a treatment option despite limited evidence in randomized controlled trials 1
• Methylphenidate - suggested based on clinical experience and limited evidence 1
• Pitolisant - a histamine H3 receptor antagonist/inverse agonist that has shown promising results 1, 3
• Sodium oxybate - recently FDA-approved specifically for idiopathic hypersomnia in adults 1, 4

Evidence for Sodium Oxybate

• In 2021, low-sodium oxybate (LXB) received FDA approval specifically for idiopathic hypersomnia in adults 4, 5
• In a placebo-controlled, double-blind, randomized withdrawal study, sodium oxybate demonstrated significant benefits in:
  • Reducing daytime sleepiness
  • Improving sleep inertia (difficulty awakening)
  • Enhancing daily functioning 4, 5
• Patients withdrawn from sodium oxybate and randomized to placebo experienced significant worsening in Epworth Sleepiness Scale scores compared to those who continued treatment 4

Treatment Selection Considerations

• Medication choice should be guided by:
  • Predominant symptom profile (excessive daytime sleepiness, sleep inertia, cognitive dysfunction)
  • Patient age
  • Comorbidities (especially cardiovascular problems or depression)
  • Potential drug interactions with other medications 5
• Side effect profiles differ between medications and should be considered when selecting treatment:
  • Modafinil may cause more side effects than placebo, though the difference does not always reach statistical significance 2
  • Sodium oxybate requires special risk evaluation and mitigation strategies due to its potential for abuse 4

Treatment Monitoring

• Regular assessment of treatment efficacy is essential as response may change over time 6
• The Idiopathic Hypersomnia Severity Scale (IHSS) has been validated specifically for IH and can be used to monitor treatment response 4, 5
• Patients on sodium oxybate who were withdrawn from treatment showed significant worsening in IHSS scores, demonstrating the importance of continued therapy 4

Practical Considerations

• For sodium oxybate, dosing regimens can be once nightly or twice nightly depending on clinical presentation:
  • Once nightly dosing may be appropriate for patients with difficulty awakening or long sleep time
  • Twice nightly dosing may be better for patients with disrupted nighttime sleep 4
• Non-pharmacologic approaches should complement medication therapy, including scheduled napping and sleep hygiene techniques 7, 8

Treatment Challenges

• Despite these guidelines, management of idiopathic hypersomnia remains challenging due to:
  • Limited disease-specific assessments until recently
  • Reliance on case series rather than large randomized controlled trials
  • Lack of understanding of the underlying pathophysiology 5, 3