National Sleep Foundation

Chapter 4: Primary Hypersomnias

Treatment: Pharmacologic Treatment

Treating narcolepsy usually involves the use of a variety of medications.

Excessive Daytime Sleepiness (EDS) in patients who have narcolepsy is usually managed with traditional central nervous system (CNS) stimulants. Successful treatment depends on developing an acceptable balance between the stimulants’ wake-promoting effects and their side-effects (e.g., anxiety, tremors, and anorexia). Modafinil or its R-enantiomer, armodafinil (both wakefulness-promoting agents) is currently the initial treatment of choice due to its proven efficacy, favorable side effect profile, and low potential for abuse.41, 42, 43, 44  Armodafinil maintains higher plasma concentrations later in the day, which may result in improved wakefulness.44

If treatment with modafinil or armodafinil is unsuccessful, stimulants such as methylphenidate or dextroamphetamine may be prescribed, often in their extended-release formulations.46

Sodium oxybate (gamma hydroxybutyrate [GHB]) is currently the only FDA-approved drug (Xyrem®), to treat cataplexy.47, 48  It is a strong sleep-inducing agent and can be used if cataplexy remains despite therapy with stimulants. Sodium oxybate’s common side effects include dizziness, headache, nausea, vomiting, confusion, and urinary incontinence. Long-term treatment efficacy with no evidence of tolerance to cataplectic effects has been demonstrated.49, 50

Tricyclic antidepressants (TCAs) (e.g., clomipramine and imipramine), and Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g., fluoxetine and paroxetine) are often used to treat cataplexy, although they show varied efficacy in doing so and have not been approved by the Food and Drug Administration for this indication.  They may also decrease hypnagogic hallucinations and sleep paralysis.52 As a class, SSRIs are less effective anti-cataplectics than TCAs, but are safer and better tolerated.53, 54

References

  1. US Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil as a treatment for excessive daytime somnolence in narcolepsy. Neurology. 2000;54:1166-1175.
  2. Jasinski DR, Kovacevic-Ristanovic R. Evaluation of the abuse liability of modafinil and other drugs for excessive daytime sleepiness associated with narcolepsy. Clin Neuropharmacol. 2000;23:149-156.
  3. Mignot E, “Narcolepsy: Pharmacology, Pathophysiology, and Genetics,” In Kryger M, Roth T, Dement W (ed.), Principles and Practice of Sleep Medicine (5th Edition), St. Louis: Elsevier Saunders, 2011, pages 938-956.
  4. National Sleep Foundation, “Sleep Related Problems: Narcolepsy and Sleep,” Arlington, VA: NSF, no date. Online at: http://sleepfoundation.org/sleep-topics/sleep-related-problems.
  5. Darwish M1, Kirby M, Hellriegel ET, Robertson P Jr., “Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies,” Clin Drug Investig. 2009;29(9):613-23. doi: 10.2165/11315280-000000000-00000.
  6. Silber MH, Krahn LE, Morgenthaler TJ. Sleep Medicine in Clinical Practice. London, England: Taylor and Francis; 2004.
  7. Mignot E, “Narcolepsy: Pharmacology, Pathophysiology, and Genetics,” In Kryger M, Roth T, Dement W (ed.), Principles and Practice of Sleep Medicine (5th Edition), St. Louis: Elsevier Saunders, 2011, pages 938-956.
  8. National Sleep Foundation, “Sleep Related Problems: Narcolepsy and Sleep,” Arlington, VA: NSF, no date. Online at: sleepfoundation.org.
  9. US Xyrem Multicenter Study Group. A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. Sleep. 2002;25:42-49.
  10. US Xyrem Multicenter Study Group. Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med. 2004;5:119-123.
  11. Houghton WC, Scammell TE, Thorpy M. Pharmacotherapy for cataplexy. Sleep Med Rev. 2004;8:355-366.
  12. Guilleminault C and M Fromherz, “Narcolepsy: Diagnosis and Management,” In Kryger M, Roth T, Dement W (ed.), Principles and Practice of Sleep Medicine (5th Edition), St. Louis: Elsevier Saunders, 2011, pages 957-968.
  13. Houghton WC, Scammell TE, Thorpy M. Pharmacotherapy for cataplexy. Sleep Med Rev. 2004;8:355-366.
  14. Guilleminault C and M Fromherz, “Narcolepsy: Diagnosis and Management,” In Kryger M, Roth T, Dement W (ed.), Principles and Practice of Sleep Medicine (5th Edition), St. Louis: Elsevier Saunders, 2011, pages 957-968.