Table 4.

Currently available treatments for narcolepsy

Drug	Indication	Mechanism of action	Advantages	Disadvantages
Modafinil	Improve wakefulness in adults with excessive sleepiness associated with narcolepsy, OSA, or shift-work disorder [93]	Weak inhibitor of dopamine reuptake [111]	Lower potential for abuse than some other stimulants [3, 111]	Interferes with oral contraceptives [3] Drug-induced rash [3, 76, 93]
Armodafinil	Improve wakefulness in adults with excessive sleepiness associated with narcolepsy, OSA, or shift-work disorder [112]	Indirect dopamine receptor agonist [112]	Lower potential for abuse than some other stimulants [3]	Interferes with oral contraceptives [3] Drug-induced rash [3, 76, 112]
Methylphenidate	Treatment of ADHD and EDS in narcolepsy [74, 113]	Increases dopamine and norepinephrine transmission [74]		Potential for abuse [113] AEs (e.g., irritability, nervousness, heart rhythm disturbances, nighttime sleep disruption) [113, 114]
Amphetamines	Treatment of EDS in narcolepsy [3]	Enhanced release of dopamine and, to a lesser extent, norepinephrine from presynaptic terminals and inhibition of their reuptake [55]		Potential for abuse [3, 114] AEs (e.g., irritability, overstimulation, shakiness, CV AEs [such as tachycardia and hypertension], nighttime sleep disruption) [3, 55]
Oxybates	Treatment of EDS or cataplexy in patients with narcolepsy [79, 80]	GABAB receptor agonist in the CNS [74]	Can be used in children ≥ 7 years old [79, 80] A low-sodium formulation is available [80, 84]	Potential for abuse Requires twice-nightly dosing [3, 74] Risk of CNS and respiratory suppression; risk of anxiety and other psychiatric AEs [79, 80]
Pitolisant	Treatment of EDS or cataplexy in adults with narcolepsy [86]	Histamine H3 receptor antagonist/inverse agonist [85, 86]	Low rates of treatment-emergent AEs [84]	Interferes with oral contraceptives [86]
Solriamfetol	Improve wakefulness in adults with EDS associated with narcolepsy or OSA [88]	Selective inhibitor of the reuptake of dopamine and norepinephrine; does not promote the release of monoamines [74, 76]	Does not interfere with oral contraceptives [76, 84] May improve alertness better than other agents [84]	Increases BP and HR [84, 88] May be associated with psychiatric symptoms [88] Interacts with MAO inhibitors and dopaminergic drugs [88]
SNRIs, venlafaxine	Off-label treatment of cataplexy in narcolepsy [3, 74]	Selective norepinephrine reuptake inhibitor [84]	Fewer AEs than with TCAs [84] Available in extended-release formulation [115]	AEs (insomnia, mental stimulation, reduced sexual function) [3, 115] Rebound cataplexy following withdrawal [74]

ADHD attention-deficit hyperactivity disorder, AEs adverse events, BP blood pressure, CNS central nervous system, CV cardiovascular, EDS excessive daytime sleepiness, GABA_B gamma-hydroxybutyric acid B, HR heart rate, MAO monoamine oxidase, OSA obstructive sleep apnea, SNRIs selective norepinephrine reuptake inhibitors, TCAs tricyclic antidepressants