For a patient with OSA, residual hypersomnolence, depression, PTSD, alcohol dependence, and a seizure disorder, allergic to armodafinil (Nuvigil), is soriamfetol or pitolisant a better choice for residual hypersomnolence?

Pitolisant is Preferred Over Solriamfetol for OSA Residual Hypersomnolence in a Patient with Seizure Disorder

For a patient with OSA, residual hypersomnolence, depression, PTSD, alcohol dependence, seizure disorder, and vivid dreams who has an allergy to armodafinil, pitolisant is the better choice over solriamfetol due to its favorable safety profile in patients with seizure disorders.

Rationale for Choosing Pitolisant

Safety in Seizure Disorders

• Pitolisant works through histaminergic pathways rather than adrenergic pathways, making it less likely to lower seizure threshold 1
• Pitolisant is the only wake-promoting medication not scheduled as a controlled substance by the DEA 2, which is particularly important for a patient with alcohol dependence
• Unlike traditional psychostimulants, pitolisant has not been associated with worsening seizure disorders in patients with current seizure disorder 3

Efficacy for OSA Residual Hypersomnolence

• The American Academy of Sleep Medicine strongly recommends pitolisant for the treatment of narcolepsy and conditionally recommends it for idiopathic hypersomnia 2
• Pitolisant significantly reduces daytime sleepiness in OSA patients with residual sleepiness despite CPAP adherence, as demonstrated in a randomized controlled trial 4
• Long-term (1-year) data shows sustained efficacy and good safety profile for pitolisant in OSA patients with residual sleepiness 5

Concerns with Solriamfetol

• As a norepinephrine-dopamine reuptake inhibitor, solriamfetol has more potential to affect seizure threshold compared to pitolisant
• Solriamfetol is a controlled substance (Schedule IV), which raises concerns given the patient's alcohol dependence history
• The patient's allergy to armodafinil may indicate potential cross-reactivity with other stimulant medications

Management Approach

1. Start with pitolisant:

   • Begin at 4.45 mg once daily in the morning for 1 week
   • Titrate to 8.9 mg daily for week 2
   • Increase to 17.8 mg daily if needed for adequate response
   • Maximum dose: 35.6 mg daily

2. Monitor for:

   • Improvement in Epworth Sleepiness Scale scores (target score <10)
   • Seizure frequency and severity
   • Psychiatric symptoms (given depression and PTSD history)
   • Sleep quality and vivid dreams
   • Potential drug interactions with concurrent medications

3. Adjunctive measures:

   • Ensure optimal CPAP adherence and efficacy
   • Maintain regular sleep-wake schedule
   • Consider scheduled short naps (15-20 minutes) during the day if needed
   • Avoid alcohol (important for both seizure control and sleep quality)

Important Considerations

• Alcohol dependence: Pitolisant is not a controlled substance and has lower abuse potential compared to solriamfetol
• Vivid dreams: Monitor for any worsening of dream intensity, which can occur with wake-promoting agents
• Depression and PTSD: Pitolisant has fewer psychiatric side effects than traditional stimulants
• Drug interactions: Check for interactions with any antiepileptic drugs, antidepressants, or other medications the patient is taking

Potential Adverse Effects of Pitolisant

• Common side effects include headache, insomnia, nausea, and anxiety 2, 4
• No significant cardiovascular safety concerns have been reported in long-term studies 5, 4
• May reduce effectiveness of hormonal contraceptives (not relevant in this case)

By choosing pitolisant over solriamfetol, you're prioritizing seizure safety while effectively addressing the residual hypersomnolence in this complex patient with multiple comorbidities.