Unmet needs of patients with narcolepsy: perspectives on emerging treatment options

Figures & data

Table 1 Selected compounds used in narcolepsy

Compound	Mechanism of actiona	Usual total daily doses	Indication	Level of evidenceb
Amphetamines (dexamphetamine, methamphetamine)	Increase monoamine release: DA > NA >> 5-HT by reverse efflux of DA via DAT and inhibition of monoamine storage via VMAT	5–60 mg	EDS	III, V
Methylphenidate	Blocks monoamine (DA > NA >> 5-HT) uptake	20–40 mg	EDS	II, V
Modafinil	Not fully determined. Probably selective DA reuptake inhibition	100–400 mg	EDS	I, II
Armodafinil	As for modafinil	50–250 mg	EDS	I
Tricyclic antidepressants			Cataplexy	IV, V
Clomipramine	Blocks reuptake of 5-HT > NA >> DA	10–150 mg
Imipramine	Blocks reuptake of NA = 5-HT	10–100 mg
Fluoxetine	Blocks reuptake of 5-HT >> NA = DA	10–40 mg	Cataplexy	II, V
Venlafaxine	Blocks reuptake of 5-HT ≥ NA	75–375 mg	Cataplexy	IV
Duloxetine	Similar to venlafaxine	30–60 mg	Cataplexy	IV
Ritanserin	5-HT2 antagonist	5–10 mg	EDS	II
Reboxetine	Blocks NA reuptake	2–10 mg	Cataplexy	IV
Sodium oxybate	Unclear. Probably acts via GABA-B or specific GHB receptors	4.5–9 g	Cataplexy	I, IV
			EDS	I, IV
			Sleep disruption	I, IV
			Sleep paralysis	IV
			Hypnagogic hallucinations	IV

Notes: I. Randomized, well-designed trials with low alpha and beta error, or meta-analyses of randomized controlled trials with homogeneity of results. II. Randomized trials with high alpha and beta error, methodologic problems, or high quality cohort studies. III. Nonrandomized concurrently controlled studies (case–control studies). IV. Case–control or cohort studies with methodological problems, or case series. V. Expert opinion, or studies based on physiology or bench research.

a Adapted from Mignot EJ. A practical guide to the therapy of narcolepsy and hypersomnia syndromes. Neurotherapeutics. 2012;9(4):739–752.²⁰

b Copyright © 2015. American Academy of Sleep Medicine. Adapted from Morgenthaler TI, Kapur VK, Brown T, et al; Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007;30(12):1705–1711.¹⁶

Abbreviations: 5-HT, serotonin; DA, dopamine; DAT, dopamine transporter; EDS, excessive daytime sleepiness; GABA-B, γ-aminobutyric acid type B; GHB, gamma hydroxybutyrate; NA, noradrenaline; VMAT, vesicular monoamine transporter.

MignotEJA practical guide to the therapy of narcolepsy and hypersomnia syndromesNeurotherapeutics20129473975223065655

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MorgenthalerTIKapurVKBrownTStandards of Practice Committee of the American Academy of Sleep MedicinePractice parameters for the treatment of narcolepsy and other hypersomnias of central originSleep200730121705171118246980

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