What is the medication of choice for a patient with idiopathic hypersomnia (IH) and a seizure disorder?

Medication Choice for Idiopathic Hypersomnia with Seizure Disorder

Modafinil is the recommended first-line medication for patients with idiopathic hypersomnia who also have a seizure disorder. 1

Rationale for Modafinil as First Choice

• Modafinil has received a STRONG recommendation from the American Academy of Sleep Medicine (AASM) for the treatment of idiopathic hypersomnia, making it the preferred first-line agent 1
• Modafinil has demonstrated clinically significant improvements in:
  • Excessive daytime sleepiness 1, 2
  • Disease severity 1, 3
  • Ability to remain awake (as measured by the Maintenance of Wakefulness Test) 2, 4
• Modafinil does not have known interactions with antiepileptic drugs and does not lower the seizure threshold, making it suitable for patients with seizure disorders 1

Evidence Supporting Modafinil

• High-quality randomized controlled trials have shown that modafinil significantly improves self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (high-certainty evidence) 3
• Modafinil improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points compared to placebo (moderate-certainty evidence) 3
• A 2021 multicenter, randomized, double-blind, placebo-controlled study showed modafinil significantly prolonged mean sleep latency on the Maintenance of Wakefulness Test compared with placebo (5.02 min, 95% CI: 3.26-6.77 min; p < 0.001) 2

Dosing Recommendations

• Starting dose: 100 mg once upon awakening in the morning 1
• Dose can be increased at weekly intervals as necessary 1
• Typical effective dose range: 200-400 mg per day 1
• Consider divided dosing (morning and noon) if needed for all-day coverage 4

Monitoring and Follow-up

• More frequent follow-up is necessary when starting medication or adjusting doses 1
• Monitor for:
  • Adverse effects including headaches, nausea, and nervousness 1, 2
  • Residual sleepiness using the Epworth Sleepiness Scale 1
  • Functional ability improvements 1

Alternative Options (If Modafinil Is Not Effective or Tolerated)

If modafinil is ineffective or poorly tolerated, consider these alternatives in order of preference:

1. Methylphenidate (conditional recommendation) 1

   • Demonstrated clinically significant improvement in disease severity 1
   • Monitor for common side effects: dry mouth, sweating, headache, loss of appetite, and stomach discomfort 1

2. Pitolisant (conditional recommendation) 1

   • Newer agent with promising results 1, 5
   • May have a favorable side effect profile compared to stimulants

3. Sodium oxybate (conditional recommendation) 1

   • Consider carefully in patients with seizure disorders due to potential CNS effects

Important Considerations and Precautions

• Modafinil is an FDA Schedule IV controlled substance due to potential for abuse or dependency 1
• Common adverse events include:
  • Headache (most common) 2, 6
  • Nausea 1, 2
  • Nervousness 1, 6
  • Dry mouth 2, 6
  • Gastrointestinal disorders 4, 6
• Special precautions:
  • May reduce effectiveness of oral contraceptives 1
  • Contraindicated in pregnancy based on animal data showing potential fetal harm 1

When to Refer to a Sleep Specialist

• When idiopathic hypersomnia is suspected or the cause of sleepiness is unknown 1
• For complex patients who are unresponsive to initial or subsequent therapy 1
• When management of both seizure disorder and hypersomnia requires specialized expertise