CNS stimulants tend to be less effective for IH than they are for narcolepsy and may be less well tolerated. Stimulants
The main treatment of excessive daytime sleepiness is done through central nervous system stimulants. Methylphenidate and Dextroamphetamine are most used stimulants to controlled EDS. Increased dopamine release is felt to be the main property explaining wake-promotion from these medications. Insomnia is another common side effect and may require additional treatment. Non-stimulant wake-promoting medications
Solriamfetol is the first and only dual-acting dopamine and norepinephrine reuptake inhibitor approved by the FDA to improve wakefulness in adults living with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.Pitolisant, a selective histamine 3 (H3) receptor antagonist/inverse agonist, was approved by FDA during August 2019. It works by increasing the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain. Modafinil and Armodafinil elevate hypothalamic histamine levels, and they are known to bind to the dopamine transporter, thereby inhibiting dopamine reuptake. Modafinil can cause uncomfortable side effects, including nausea, headache, and a dry mouth for some patients, while other patients report no noticeable improvement even on relatively high dosages. They may also "interact with low-dose contraceptives, potentially reducing efficacy, although the scientific data supporting this claim is weak and rests on poorly documented anecdotes." Sleep promoting medications
Sodium oxybate is an orphan drug which was designed specifically for the treatment of narcolepsy. Common side effects include nausea, dizziness, and hallucinations. A 2016 study by Leu-Semenescu et al.
The bottom-up pathway emerges from the ascending reticular arousal system (ARAS) and activates the cortex via well-characterized thalamic and nonthalamic pathways through cholinergic and aminergic neurotransmission. The bottom-up pathway represents the leverage point for pharmaceutical interventions. It is complemented by a corticothalamic top-down pathway, which appears to be modifiable through noninvasive brain stimulation (NIBS) techniques. A single case report study indicates that high-frequency repetitive transcranial magnetic stimulation (HF rTMS) over the left dorsolateral prefrontal cortex (DLPFC) might represent an alternative choice for symptom control in narcoleptic patients with cataplexy. rTMS may also exert intrinsic effects on hypersomnia in depressed adolescents. Mazindol
Mazindol is a stimulant similar to amphetamines that "has been shown to be effective in treating hypersomnia in narcoleptics." However, it is not currently approved in the US. Selegiline
Selegiline, monoamine oxidase type B (MAO-B) inhibitor works by slowing the breakdown of certain substances in the brain (mostly dopamine, but also serotonin and norepinephrine). It may also be useful, as it is also a metabolic precursor of amphetamine and exerts most of its therapeutic effects through amphetamine metabolism. It is not commonly prescribed for people with narcolepsy because of the high dosage required and potential for severe side effects. Atomoxetine
Atomoxetine (or reboxetine in Europe) is an adrenergic reuptake inhibitor which increases wakefulness (generally less strongly than the medications which act on dopamine) and which has been argued to have a "clear use in the therapeutic arsenal against narcolepsy and hypersomnia although undocumented by clinical trials."