No single therapy will control all the symptoms. Narcolepsy responds best to (1) strategically placed 15to 20-min naps (during lunch hour, before or after dinner, etc.); (2) the use of stimulant drugs in the daytime—modafinil, dextroamphetamine sulfate, or methylphenidate hydrochloride to heighten alertness; and (3) antidepressants (sertraline, venlafaxine, protriptyline, imipramine, or clomipramine) for control of cataplexy. All these drugs are potent suppressants of REM sleep. Monoamine oxidase (MAO) inhibitors also inhibit REM sleep and can be used if they are tolerated. Modafinil (200 mg daily, up to 600 mg in divided doses) may prove to be the safest of the stimulants (Fry), but experience with this agent is still being acquired. Methylphenidate, because of its prompt action and relative lack of side effects, is also widely used. It is usually given in doses of 10 to 20 mg tid on an empty stomach. Alternatively, amphetamine 5 to 10 mg may be given 3 to 5 times a day; this is ordinarily well tolerated and does not cause wakefulness at night. Pemoline, a potent stimulant (50 to 75 mg daily) is no longer available in the United States because of potential hepatic toxicity. The tricyclic antidepressants had been used to reduce cataplexy, but they have been overtaken by selective serotonin reuptake inhibitors such as sertraline and by norepinephrine reuptake inhibitors such as venlafaxine. Sodium oxybate, whose active agent is gamma-hydroxybutyrate, is also beneficial for cataplexy and narcolepsy in many individuals.
The combined use of these stimulant and tricyclic antidepressant drugs may be indicated. A problem with the stimulant drugs is the development of tolerance over a 6to 12-month period, which requires the switching and periodic discontinuation of drugs. Excessive amounts of amphetamines may induce a schizophreniform psychosis. The stimulant drugs and the tricyclic antidepressants increase catecholamine levels; their chronic administration may produce hypertension.
An entirely different approach, based on a presumed autoimmune attack on hypothalamic neurons, has introduced immune globulin infusions in early cases of narcolepsy. This must still be considered preliminary but the results are interesting (see Dauvillers et al, 2004).
Narcoleptics must be warned of the dangers of falling asleep and lapses of consciousness while driving or during engagement in other activities that require constant alertness. The earliest feeling of drowsiness should prompt the patient to pull off the road and take a nap. Long-distance driving should probably be avoided completely.
As has been indicated, recurrent daytime sleepiness may be the presenting symptom in a number of varied disorders other than narcolepsy. When chronic daytime sleepiness occurs repeatedly and persistently without known cause, it is classified as essential or idiopathic hypersomnolence. Roth distinguishes this state from narcolepsy on the basis of longer and unrefreshing daytime sleep periods, deep and undisturbed night sleep, difficulty in awakening in the morning or after a nap (“sleep drunkenness”), all of these occurring in the absence of REM-onset sleep and cataplexy. Admittedly, this condition proves difficult to distinguish from narcolepsy unless laboratory studies exclude the latter, and even then, there is overlap between the two syndromes (Bassetti and Aldrich). Treatment, however, is the same as that for narcolepsy. Idiopathic hypersomnia, as defined in this manner, proves to be a rare syndrome once narcolepsy and all other causes of daytime sleepiness have been excluded.