Drug Criteria & Outcomes
An Awakening to Narcolepsy
By Lori Lawson, PharmD Candidate, Harrison School of Pharmacy, Auburn University
Narcolepsy is a chronic neurological disorder, mistakenly thought to occur only rarely. However, approximately 5% of patients seen at the American Academy of Sleep Medicine in the United States have this disease and it is estimated that as many as one in 2,000 Americans have narcolepsy.1,2
Narcolepsy is characterized by uncontrollable sleepiness and intermittent manifestations of REM sleep at periods when a person should normally be awake. Most patients also experience cataplexy, which is partial or generalized loss of skeletal muscle tone and power in response to emotion, especially amusement, anger, and elation. Other common symptoms include: sleep paralysis, hypnagogic hallucinations (vivid, dream-like experiences at the start of sleep), disturbed nocturnal sleep, and automatic behavior.3
This disease has many clinical facets. Sleep attacks can occur at any time and can be very disabling. Patients may involuntarily fall asleep while driving, eating, working, or talking. Hence, this is a dangerous disease that could lead to accidents and loss of employment.
Researchers have identified a potential biochemical basis of narcolepsy. In humans, hypocretin, a neurotransmitter, is reduced or undetectable in many but not all patients with narcolepsy associated with cataplexy. Research data on hypocretin continue to be accumulate and in the future hypocretin therapy may be an option.
Treatment options
Treatment can make a significant difference in these patients' lives. The excessive daytime sleepiness is most commonly treated with stimulants. In 1999, the FDA approved modafinil (Provigil®), a novel stimulant with an unclear mechanism of action that may increase hypocretin activity. Apart from modafinil, all stimulants are centrally acting sympathomimetic agents that increase the release of monoamines in the synaptic cleft and block their reuptake.4 Modafinil is now considered first-line treatment for narcolepsy.2 Modafinil is not a psychostimulant and it does not cause psychomotor agitation, disruption of night-time sleep, inappropriate mood shifts, or the potential for addiction. In June 2007, the FDA approved the active isomer of modafinil, armodafinil (Nuvigil®), also indicated for narcolepsy. Armodafinil has very similar pharmacokinetics, dosing, and adverse effects as compared to modafinil, and at this time, armodafinil appears to have no clinical advantages over modafinil.5,6
Other stimulants used to treat excessive daytime sleepiness include amphetamine, methamphetamine, dextroamphetmaine, and methylphenidate.1 These drugs can cause insomnia, hypertension, palpitations, and irritability. However, many patients tolerate these drugs without significant side effects. Tolerance to these medications may also occur, necessitating an increase in dose to achieve the same control of symptoms.2
The goal of stimulant therapy is to treat to near normal alertness with minimal adverse effects. Dosages should be started out low and increased as needed and as tolerated. Many physicians are weary of increasing the dose for fear of inducing tolerance or dependence. While tolerance does occur in some patients, abuse is rare in patients who do not have a history.4
Selegiline, a monoamine oxidase inhibitor, is an effective treatment for all narcoleptic symptoms. However, experience with the high doses needed for narcolepsy is limited and diet-induced hypertension is a danger at effective doses.1
Unfortunately, stimulants do not treat cataplexy effectively. Common drug therapies include tricyclic antidepressants such as protriptyline, imipramine, and clomipramine, and selective serotonin reuptake inhibitors such as fluoxetine and paroxetine. Sodium oxybate or gammahydroxybutyrate (GHB) was granted FDA approval in 2002 for the treatment of cataplexy and daytime sleepiness in patients with narcolepsy. It is an old sedative drug with considerable abuse potential, and is available only from one national specialty pharmacy on a named-patient basis. Sodium oxybate is a neurotransmitter found in the brain, and research demonstrates that nightly administration of sodium oxybate helps produce sleep patterns more closely resembling normal sleep patterns.2
Nonpharmacological therapies include maintaining regular sleep and wake times, avoiding shift work, and working in a stimulating environment. It is often said that naps throughout the day are helpful, but objective data are contradictory.1
References
- Littner M, Johnson S, McCall V, et al. Practice parameters for the treatment of narcolepsy: An update for 2000. Sleep 2001;24:451-466.
- Feldman N. Narcolepsy. South Med J 2003;96:277-282.
- Zeman A, Britton T, Douglas N, et al. Narcolepsy and excessive daytime sleepiness. BMJ 2004;329:724-728.
- Krahn L, Black J, Silber H. Narcolepsy: New understanding of irresistible sleep. Mayo Clin Proc 2001;76:185-194.
- Lexi-Drugs. Hudson, OH: Lexi-Comp, Inc.; 2007.
- Harsh J, Hyaduk R, Wesnes K, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin 2006;22:761-774.
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