Drugs used in the treatment of narcolepsy

Drug	Dosage, usual (adult)	Common side effects	Serious side effects
Excessive daytime sleepiness
Modafinil	100 to 400 mg every morning or 200 mg twice per day	Headache, nervousness, nausea, insomnia	Severe rash
Armodafinil	150 to 250 mg every morning or 125 mg (half of 250 mg tablet) twice per day	Headache, nervousness, nausea, insomnia	Severe rash
Solriamfetol	75 to 150 mg every morning	Headache, nausea, reduced appetite	Cardiovascular effects
Pitolisant*	8.9 to 35.6 mg once per day	Headache, insomnia, nausea, anxiety	Severe rash, QT prolongation
Methylphenidate	10 to 30 mg twice per day or 20 mg extended release every morning with 10 to 20 mg immediate or extended release every afternoon^¶	Reduced appetite, nausea, headache, insomnia	Abuse potential, psychosis, mania, seizures, cardiovascular effects^Δ
Dextroamphetamine	5 to 30 mg twice per day or 10 mg extended release every morning with 10 to 20 mg immediate or extended release every afternoon^¶	Reduced appetite, nausea, headache, insomnia	High abuse potential, psychosis, mania, seizures, cardiovascular effects^Δ
Amphetamine-dextroamphetamine	10 to 30 mg twice per day or 20 mg extended release twice per day^¶	Reduced appetite, nausea, headache, insomnia	High abuse potential, psychosis, mania, seizures, cardiovascular effects^Δ
Amphetamine sulfate	10 to 60 mg per day in two or three divided doses	Reduced appetite, nausea, headache, insomnia	High abuse potential, psychosis, mania, seizures, cardiovascular effects^Δ
Oxybates (gamma hydroxybutyrate)	2.25 to 4.5 grams at bedtime and repeated 3 to 4 hours later	Morning sedation, nausea, dizziness, urinary incontinence, sleepwalking	Abuse potential, confusion, severe sedation, coma^◊
Cataplexy^§
Venlafaxine	37.5 to 75 mg twice per day or 37.5 to 150 mg extended release every morning	Transient nausea, headache, insomnia, increase in blood-pressure when given in higher doses
Fluoxetine	20 to 80 mg every morning	Nausea, dry mouth, insomnia	QT prolongation
Clomipramine	10 to 150 mg as a single dose every morning or in divided doses	Dry mouth, constipation, sweating, dizziness, somnolence, weight gain, orthostatic hypotension	Cardiotoxicity, seizures, dangerous in overdose^¥
Protriptyline	5 to 60 mg as a single dose every morning or in divided doses	Dry mouth, constipation, sweating, anxiety, disturbed nighttime sleep, orthostatic hypotension	Cardiotoxicity, seizures, dangerous in overdose^¥
Pitolisant	8.9 to 35.6 mg once per day	Headache, insomnia, nausea, anxiety	Severe rash, QT prolongation
Oxybates (gamma hydroxybutyrate)	2.25 to 4.5 grams at bedtime and repeated 3 to 4 hours later	Morning sedation, nausea, dizziness, urinary incontinence, sleepwalking	Abuse potential, confusion, severe sedation, coma^◊
Disrupted nighttime sleep^‡
Zolpidem	5 to 10 mg at bedtime	Morning sedation, dizziness
Oxybates (gamma hydroxybutyrate)	2.25 to 4.5 grams at bedtime and repeated 3 to 4 hours later	Morning sedation, nausea, dizziness, urinary incontinence, sleepwalking	Abuse potential, confusion, severe sedation, coma^◊

Most of the medications listed in this table require gradual dose titration and administration at specific scheduled times to optimize patient response. For details, refer to the topic review and the Lexicomp individual drug monographs.

* Also has anti-cataplexy effects.
¶ Although extended release formulations are intended to be taken once daily, many patients with narcolepsy find that the clinical effect wears off in four to six hours, necessitating a second dose in the early afternoon.
Δ For additional information refer to topic review of treatment of attention deficit hyperactivity disorder in adults or adolescents, section on adverse effects.
◊ Combined use with alcohol, sedatives, or hypnotics is specifically contraindicated in US licensing information.
§ Anti-cataplexy medications are also useful for problematic sleep paralysis or hypnagogic hallucinations.
¥ For additional information refer to topic review of tricyclic antidepressants, section on adverse effects.
‡ Some sleep disruption in narcolepsy may be caused by additional sleep disorders that require specific treatment (examples include obstructive sleep apnea or periodic limb movements of sleep).

Adapted from: Scammell TE. The Neurobiology, diagnosis, and treatment of Narcolepsy. Ann Neurol 2003; 53:154.

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