When to consider narcolepsy
Narcolepsy is a CNS disease characterized by abnormal regulation of REM sleep. EDS—the cardinal symptom—is often associated with cataplexy (75%), sleep paralysis (50%), vivid dreams, and insomnia, all of which interfere with REM phenomena. Narcolepsy affects 0.05% of the U.S. population and can lead to severe occupational, educational, and family disruption.
When you obtain a history that suggests narcolepsy, use the history, a sleep diary, or wrist actigraphy to document whether the patient is getting adequate sleep, with a consistent sleep/wake cycle. Next, consider referring the patient for polysomnography, primarily to rule out other causes of EDS such as sleep-disordered breathing. In some cases, REM latency on the overnight sleep study will be <20 minutes after sleep onset, which supports the diagnosis of narcolepsy.
A multiple sleep latency test (MSLT)—a diagnostic session in which the patient takes 4 to 5 daytime naps—is performed the following day. Narcolepsy is confirmed if the patient has a mean initial sleep latency of <10 minutes during these naps plus at least two REM episodes within 15 minutes after sleep onset.
When to refer your patient to a sleep disorder center
The 4 most appropriate indications for an urgent sleep evaluation are:
- difficulty staying alert while driving
- nocturnal cardiac arrhythmias
- frequent observed apneas
- excessive daytime sleepiness (EDS) leading to academic or occupational problems.
Insurance companies usually cover a specialty sleep evaluation, particularly if the referring physician documents a suspicion of sleep-disordered breathing or EDS that jeopardizes safe driving.
Most patients with narcolepsy and cataplexy have undetectable cerebrospinal fluid levels of a neuropeptide called hypocretin or orexin.17 Hypocretin/orexin replacement therapy is a theoretical possibility, but for now treatment includes a combination of optimal sleep hygiene, psychostimulants, antidepressants, and hypnotics.
Other causes of EDS
EDS can also be caused by unrecognized alcohol dependence, inappropriate or excessive medication use, and depressive disorders. Overnight sleep studies are seldom indicated unless patients endorse the symptoms in the Figure.
Before pursuing polysomnography or an MSLT (Box 4), eliminate medications that might confound the results, such as:
- antidepressants, which alter the timing and duration of REM sleep
- sedating medications, which modify initial sleep latency and sleep efficiency and potentially aggravate sleep disordered breathing.
Initial REM latency provides a potential biologic marker of major depression but is used more often in research than in clinical psychiatry.
Primary insomnia is the distressing inability to sleep at night or nap during the day. It suggests a hyperarousal state—the opposite of EDS.18 In rare cases, however, patients who cannot sleep at night also have EDS. When evaluated, they typically endorse at least one symptom in the Figure. Sleep studies occasionally reveal OSA or restless legs syndrome.
Treating a patient with chronic insomnia may require several trials of behavioral interventions or sedating medications before you make a referral to a sleep disorder center. Patients can struggle with unrecognized primary sleep disorders for years, and many are given empiric trials of stimulating antidepressants. Antidepressants are unlikely to cause harm, but they might complicate diagnostic testing.
When you confirm coexisting depression and a primary sleep disorder, treatments that separately target each condition provide optimal management of the sleepy patient.
Medications to enhance wakefulness
Wake-promoting agents are a treatment option when EDS is contributing to compromised functioning. These drugs are no substitute for thoughtful evaluation of hypersomnolence, however. When you diagnose OSA or restless legs syndrome, first try treatments that target these conditions. If residual sleepiness persists, then consider augmenting with stimulating medications.
Modafinil is FDA-approved for residual sleepiness in patients with OSA and for shift work sleep disorder, a condition of circadian misalignment from frequent schedule changes. Evidence does not support its use for other circadian rhythm disorders, such as delayed sleep phase disorder.
Low-dose modafinil (such as 100 to 200 mg/d) is well tolerated, but its therapeutic effect as augmentation is modest.19 Increasing the dosage to >200 mg usually does not increase alertness.
Caffeine. Some patients report benefit from caffeine used in moderation and only in the morning. This practice is acceptable as long as patients do not use excessive amounts or experience insomnia, exacerbation of anxiety, or tachycardia.
Psychostimulants such as methylphenidate and amphetamines are less well-studied than modafinil for treating EDS in patients without narcolepsy. Monitor carefully for insomnia, exacerbation of anxiety, tachycardia, or hypertension and to prevent overuse of these habituating agents.
Related resources
- National Sleep Foundation. www.sleepfoundation.org.
- American Academy of Sleep Medicine. www.aasmnet.org.
- American Sleep Apnea Association. www.sleepapnea.org.
- Restless Legs Syndrome Foundation. www.rls.org.
- Association for the Study of Light Therapy and Biological Rhythms. www.sltbr.org.
Drug brand names