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Article – Narcolepsy: Diagnosis and Treatment in the Elderly

Neil T. Feldman, MD
Clinical Research Group of St. Petersburg
2525 Pasadena Avenue South, Suite S
St. Petersburg, FL  33707

Although it is sometimes debilitating and always has large negative impact on quality of life,1 narcolepsy is a nonfatal disease. Barring accidents, the life expectancy of persons with narcolepsy is not significantly different than others.2 Nevertheless, there is very little published information regarding the treatment of aging narcolepsy patients and even less information about the diagnosis of narcolepsy in this patient population.

Diagnosis

Most papers on the subject indicate the peak onset of narcolepsy occurs between 15 and 30 years of age and that onset after age 55 is uncommon.2 However, in a handful of cases, the onset of narcolepsy has been reported after 35 years of age and even after age 70. Unfortunately, there is often a long delay in diagnosis, particularly in patients without cataplexy.3 Cases after age 35 may be due to the failure to recognize the disease at an earlier age rather than late onset.4 Onset of narcolepsy after age 45 is more likely to be associated with a variety of other neurological illness such as traumatic brain injury, Parkinson’s disease and multiple sclerosis and is therefore referred to as secondary narcolepsy.4

In a review of 41 consecutive patients diagnosed with narcolepsy at one facility, 21 (51%) were more than 40 years old. Among these patients, 4 were in their 40s (19%), 9 were in their 50s (43%), 5 were in their 60s (24%) and 3 were in their 70s (14%) include one 79 year-old. Sadly, 12 of these patients reported symptoms began while they were in their teens and 20s.3

Similar to younger patients, the suspicion of narcolepsy usually begins with complaints of daytime sleepiness, disturbed nighttime sleep and by periodic muscle weakness (cataplexy) triggered by emotional events such as laughter.  The severity of narcolepsy symptoms is not affected by the age at onset;5 however, some of these symptoms may be complicated by the fact that the elderly are also more likely to experience normal age-related changes in sleep patterns,6 suffer from other sleep-related problems associated with declining physical and mental health, and the effects of various medications needed to treat those conditions.7 It should be noted that excessive daytime sleepiness is not a normal part of aging8 although it is more likely to be treated as such in the elderly.

The actual diagnosis of narcolepsy is based on overnight studies done in the sleep lab to rule out other causes of sleepiness. This is followed by the multiple sleep latency test (MSLT) where patients are offered four or five 20-min nap opportunities 2 hours apart, and the time it takes to fall asleep (sleep latency) is measured.4 As false positive and negative results frequently occur, interpretation of MSLT results should be done by an experienced physician. An average sleep onset of less than 8 minutes with 2 or more sleep-onset REM (dreaming) periods (SOREMPS) is considered diagnostic for narcolepsy; however, SOREMPS become less frequent and sleep latency increases with advancing age.4 Consequently, the MSLT may be less helpful in the diagnosis of narcolepsy in elderly patients.

Two published reports describe the onset of narcolepsy in older patients. In one case, an 87 year-old man repeatedly experienced what he described as occasional “trance-like” states accompanied by drowsiness for about 15 years. These became increasingly frequent, finally reaching 3-4 times daily. In addition, he experienced sudden “drop attacks” during the previous 3 years. During that time, he did not receive a proper diagnosis or treatment despite several hospitalizations. In the other case, a 90 year-old woman reported attacks of sudden drowsiness and slurred speech during the previous 5 years. Both of these patients were initially treated for epilepsy before receiving a proper diagnosis of narcolepsy.8

Treatment

Effective treatment is especially important because mental and social impairments caused by narcolepsy may be magnified in the elderly.4 Fortunately, narcolepsy in elderly patients may not need to be treated as aggressively as their younger counterparts because they, for example, no longer have occupational responsibilities or the need to care for young children.

Like all drugs approved by the Food and Drug Administration, the effectiveness of most medications currently used for the treatment of narcolepsy has been demonstrated in clinical trials. Unfortunately, most clinical trials exclude elderly patients for safety reasons. For example, the two clinical trials which established the effectiveness of Provigil® (modafinil) for treating sleepiness in narcolepsy enrolled 283 patients who were 18-68 years old9 and 273 patients who were 17-67 years old.10 A subsequent 40-week safety study enrolled 478 patients who were 18-65 years of age.11 Since the safety of these medications has not been established in this patient population, they must be used with a greater degree of caution.

In addition, medications must always be carefully prescribed in the elderly as they are more likely to also be using other prescription medications for treating other health-related problems. Elderly patients are more like to experience side effects and may require lower drug doses than younger patients. To make matters even worse, some prescription medications and illness can also cause sleep problems.7 Therefore, drug treatment must be carefully tailored to meet the individual needs of the elderly patient. Finally, older patients are more likely to be treated by multiple physicians and it is important for the patient to let each one know what medications have been prescribed by other physicians.

STIMULANTS

• Provigil® (modafinil)12 and Nuvigil® (armodafinil)13

These drugs have been specifically approved for improving wakefulness in patients with narcolepsy but according to the manufacturer, the safety and effectiveness of these drugs has not been established in patients over 65 years of age. During clinical trials, the most commonly-observed side effects associated with the use of Provigil and Nuvigil included headache, nausea, nervousness, anxiety, insomnia, dizziness and upset stomach. Based on the limited number of patients older than 65 years in modafinil clinical trials, the frequency of side effects was similar to younger age groups. The ability to eliminate modafinil and armodafinil from the body may be reduced in the elderly and physicians should consider using lower doses in these patients.

• Ritalin® and Ritalin-SR® (methylphenidate)14 and Dexedrine® (dextroamphetamine)15

These drugs are also approved for the treatment of drowsiness in patients with narcolepsy but should be used with caution in elderly patients. The most common side effects are nervousness and insomnia but they can also increase heart rate and blood pressure and cause irregular heart beats. These effects may place elderly patients at greater risk of  stroke and heart attacks and they should not  be prescribed to patients with atherosclerosis, heart disease, or significantly elevated blood pressure. Elderly patients taking these stimulants may also be at greater risk for developing psychiatric side effects such as anxiety, hallucinations or aggressive behavior.

ANTICATAPLECTICS

• Xyrem® (sodium oxybate)16 oral solution

Xyrem is specifically approved for the treatment of treatment of excessive daytime sleepiness as well as cataplexy in patients with narcolepsy; however, once again, there is very limited experience with the use of this drug in elderly patients. In clinical trials, the most commonly reported side effects included dizziness, headache, nausea, sleep walking, confusion, vomiting, and urinary incontinence (bed wetting). Of special concern in the elderly is that 7% of patients treated with Xyrem at nightly doses of 6 – 9 grams experienced confusion which resolved soon after the drug was stopped. Other noteworthy side effects associated with Xyrem include hallucinations and agitation. Xyrem also contains high amounts of sodium which may be of concern to patients with heart disease, high blood pressure or poor kidney function.

•  Anafranil® (clomipramine), Vivactyl® (protriptylene)17 and Effexor® (venlafaxine)18

These and similar antidepressants have a long history of use for the treatment of cataplexy although none of them are approved for the treatment of narcolepsy symptoms. Many are now available in generic form. Medications in this family are known to cause a variety of side effects which may be of special concern in elderly patients, including changes in blood pressure, heart rate and heart rhythm, dry mouth, blurred vision and constipation. Mental confusion is more likely to occur in the elderly. Antidepressants can also induce or worsen REM-sleep behavior disorder (dream enacting behavior which may be violent) which commonly occur in patients with narcolepsy. In addition, these drugs are known to sometimes to  interact dangerously with some other medications. For this reason, patients should always indicate what drugs they are taking with their physicians.

In summary, diagnosing elderly patients with narcolepsy remains challenging. As patients with narcolepsy age, their symptoms should be frequency re-evaluated for the presence of other ongoing medical and sleep-related disorders. Side effects from prescribed medications are more frequent, requiring close supervision.

References

1. Ozaki A, Inoue Y, Nakajima T, et al. Health-related quality of life among drug-naïve patients with narcolepsy with cataplexy, narcolepsy without cataplexy, and idiopathic hypersomnia without long sleep time. J Clin Sleep Med 2008;4:572-578.

2. Overeem S, Mignot E, van Dijk JG, Lammers GJ. Narcolepsy: clinical features, new pathophysiologic insights, and future perspectives. J Clin Neurophysiol 2001;18:78-105.

3. Rye DB, Dihenia B, Weissman JD, et al. Presentation of narcolepsy after 40. Neurology 1998;50:459-465

4. Attarian H. Narcolepsy in the older adult. In: Goswami M, Pando-Perumal SR, Thorpy MJ, eds. Narcolepsy: A Clinical Guide. New York: Humana Press; 2009:69-76.

5. Nevsimalova S, Buskova J, Kemlink D, et al. Does age at the onset of narcolepsy influence the course and severity of the disease? Sleep Med 2009;10:967-972.

6. Wolkove N, Elkholy O, Baltzan M, Palayew M. Sleep and aging: 1. Sleep disorders commonly found in older people. CMAJ 2007;176:1299-1304.

7. Giron MS, Forsell Y, Bernsten C, et al. Sleep problems in a very old population: drug use and clinical correlates. J Gerontol A Biol Sci Med Sci 2002;57:236-240.

8. Kelly JF, Lowe DC, Taggart HM. Narcolepsy in the elderly: A forgotten diagnosis. Age Ageing 1987;16:405-408.

9. US Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998;43:88-97.

10. US Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 2000;54:1166-1175.

11. Mitler MM, Harsh J, Hirshkowitz M, Guilleminault C. Long-term efficacy and safety of modafinil (Provigil®) for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep Med 2000;1:231-243.

12. Provigil® Prescribing Information. Cephalon, Inc. Frazer, PA. March, 2008.

13. Nuvigil® Prescribing Information. Cephalon, Inc. Frazer, PA. July, 2008.

14. Ritalin® and Ritalin-SR® Prescribing Information. Novartis Pharmaceuticals Corporation, East Hanover, NJ. April, 2009.

15. Dexedrine® Prescribing Information. GlaxoSmithKline, Research Triangle Park, NC. July, 2008.

16. Xyrem® Prescribing Information. Jazz Pharmaceuticals, Inc., Palo Alto, CA. November, 2005.

17. Vivactyl® Prescribing Information. Teva Pharmaceuticals USA, North Wales, PA. October, 2008.

18. Effexor XR® Prescribing Information. Wyeth Pharmaceuticals Inc., Philadelphia, PA. July, 2009.

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Date Created: June 11th, 2010
Last Updated: August 29th, 2010

One Response to “Article – Narcolepsy: Diagnosis and Treatment in the Elderly”

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