Narcolepsy

Source: Dopp JM, Phillips BG. Sleep Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. http://accesspharmacy.com/content.aspx?aid=7990389. Accessed June 4, 2012.

• Sleep disorder characterized by excessive sleepiness and sleep attacks at inappropriate times.

• Precise cause unknown.
• Genetic component (3% of patients have first-degree relative with disorder).
• Possible environmental influences.

• The hypocretin/orexin neurotransmitter system may be involved. Autoimmune process may cause destruction of hypocretin-producing cells.

• Affects 0.03–0.06% of adult Americans.
• Incidence may be higher in men than women.
• Usually occurs in second decade of life and increases in severity through third and fourth decades.
• Can occur in children and adolescents.

• Family history of narcolepsy
• Head injury
• Obesity
• History of meningitis or encephalitis

Signs and Symptoms

• Complaints of:
  • Excessive daytime sleepiness
  • Sleep attacks that last up to 30 minutes
  • Fatigue
  • Impaired performance
  • Disturbed nighttime sleep
• Multiple arousals during the night

Means of Confirmation and Diagnosis

• Essential features include:
  • Sleep attacks
  • Cataplexy (sudden bilateral loss of muscle tone with collapse, often precipitated by emotional situations)
  • Hypnagogic hallucinations before sleep or during a sleep attack
  • Sleep paralysis (flaccid muscles with full consciousness while falling or waking from sleep)
• Sleep study demonstrating abrupt transition into REM sleep necessary for diagnosis.

• Maximize alertness during waking hours.
• Improve quality of life.

• Encourage good sleep hygiene.
• Recommend 2 or more brief daytime naps daily; as little as 15 minutes may be beneficial.

• Pharmacotherapy focuses on excessive daytime sleepiness and cataplexy (Table 1).
• Excessive daytime somnolence
  • Modafinil 200 mg each morning standard treatment.
    • No evidence of tolerance or withdrawal after abrupt discontinuation.
    • Side effects include:
      • Headache
      • Nausea
      • Nervousness
      • Insomnia
  • Armodafinil (the active R-isomer of modafinil) is also available.
  • Amphetamines and methylphenidate have higher likelihood of abuse and tolerance.
    • Side effects include:
      • Insomnia
      • Hypertension
      • Palpitations
      • Irritability
  • Selegiline may also be beneficial.
• Cataplexy
  • Most effective treatments:
    • Imipramine
    • Protriptyline
    • Nortriptyline
    • Fluoxetine
    • Venlafaxine
  • Selegiline may also improve cataplexy.
• Sodium oxybate (γ-hydroxybutyrate; potent sedative-hypnotic) improves excessive daytime sleepiness and decreases episodes of sleep paralysis, cataplexy, and hypnagogic hallucinations.
  • Taken at bedtime and repeated 2.5–4 hours later.
  • Side effects include:
    • Nausea
    • Somnolence
    • Confusion
    • Dizziness
    • Incontinence