Primary Hypersomnia Medication

Updated: Sep 05, 2018
  • Author: Adrian Preda, MD; Chief Editor: Ana Hategan, MD, FRCPC  more...
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Medication

Medication Summary

Patients often require drug therapy to treat daytime hypersomnolence. Prior to initiating therapy with stimulants, clearly establish a diagnosis and consider potential for abuse. [8, 23]

Modafinil, a wake-promoting agent, is approved for treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome (OSAHS), and shift-work sleep disorder (SWSD). [30, 31] The studies have shown significant benefits on various objective measures and subjective estimates of excessive sleepiness.

The clinical efficacy of modafinil, combined with its improved safety over CNS stimulants, has made it the most prescribed medication for the treatment of excessive sleepiness associated with narcolepsy. Unlike many other medications used for excessive sleepiness, modafinil is not known to be abused. The most common adverse event reported in clinical studies was headaches; most were transient and mild to moderate in severity. Modafinil also has the potential for interactions with other drugs metabolized via cytochrome P450 enzyme pathways.

For Kleine-Levin syndrome, somnolence can decrease with stimulants (mainly amphetamines), while neuroleptics and antidepressants are of poor benefit. Lithium, rather than carbamazepine or other antiepileptics, was found to have a higher success rate for stopping relapses. [32]

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Stimulants

Class Summary

These agents have wake-promoting activities.

Modafinil (Provigil)

Modafinil, (1:1 racemic mixture of R- and S-modafinil) improves wakefulness, though the mechanism of action remains unclear. It may act at the dopamine receptor (DAT), inhibiting dopamine reuptake and may exert stimulant effects by decreasing GABA-medicated neurotransmission. It has wake-promoting actions similar to those of sympathomimetic agents, though no direct action on dopamine receptors themselves; wakefulness is not attenuated by known dopamine antagonists.

Armodafinil (Nuvigil)

Armodafinil is an R-enantiomer of modafinil (mixture of R- and S-enantiomers). It elicits wake-promoting actions similar to those of sympathomimetic agents, although its pharmacologic profile is not identical to sympathomimetic amines and has no direct action on dopamine receptors themselves.  Wakefulness is not attenuated by known dopamine antagonists. It may act at the dopamine receptor (DAT), inhibiting dopamine reuptake and may exert stimulant effects by decreasing GABA-medicated neurotransmission. It is not a direct- or indirect-acting dopamine receptor agonist. Armodafinil is indicated for the improvement of wakefulness in individuals with excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome (OSAHS), or shift-work sleep disorder.

Methylphenidate (Ritalin, Daytrana, Methylin, Concerta)

Methylphenidate is used for symptomatic management of primary hypersomnolence whenever the patient needs to be alert or engages in activities in which hypersomnolence may be hazardous. The drug blocks the reuptake mechanism of dopaminergic neurons. Methylphenidate stimulates the cerebral cortex and subcortical structures.

Dextroamphetamine (Procentra, Dexedrine, Zenzedi)

This agent increases the amount of circulating dopamine and norepinephrine in the cerebral cortex by blocking the reuptake of norepinephrine or dopamine from the synapse.

Dextroamphetamine and amphetamine mixtures (Mydayis, Adderall XR)

This agent produces CNS and respiratory stimulation. The CNS effect may occur in the cerebral cortex and reticular activating system. Dextroamphetamine-amphetamine mixture may have a direct effect on alpha- and beta-receptor sites in the peripheral system and may also release stores of norepinephrine in adrenergic nerve terminals. The mixture contains various salts of amphetamine and dextroamphetamine. It is available as 5-, 7.5-, 10-, 12.5-, 15-, 20-, and 30mg scored tablets.

Amphetamine (Evekeo)

Amphetamines are noncatecholamine sympathomimetic amines that promote release of catecholamines from their storage sites in the presynaptic nerve terminals. Amphetamine 1:1 racemic mixture of dextroamphetamine and levoamphetamine (immediate release only) has an FDA indication for promoting wakefulness in narcolepsy.

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