[10][11][12] Some studies have shown increased frequencies of palpitations, digestive problems, difficulty with body temperature regulation, and other symptoms in patients with IH.
[15] A case series in 2010 found that peripheral vascular symptoms, such as cold hands and feet (e.g., Raynaud syndrome), were more common in people with IH than in controls.
[17] Other autonomic dysfunctional symptoms, such as fainting episodes, dizziness upon arising, possibly migrainous headaches, food cravings, and impotence may also be correlated with IH.
[21] Researchers have recently found an abnormal hypersensitivity to GABA (the major brain chemical responsible for sedation) in a subset of patients with central hypersomnia i.e.: IH, narcolepsy without cataplexy and long sleepers.
Although this substance requires further identification of its chemical structure, it is currently referred to as a "somnogen" because it has been shown to cause hyper-reactivity of GABAA receptors, which leads to increased sedation or somnolence.
Therefore, when IH is suspected, researchers suggest appending a 24-hour continuous polysomnography to the standard overnight/MSLT study in order to record total sleep time.
[29] It is also important to note that whereas narcolepsy is strongly associated with the HLA-DQB1*0602 genotype,[20] "HLA typing is of no help in the positive diagnosis of idiopathic hypersomnia.
Affected individuals experience difficulty with awakening in the morning and may have associated sleep drunkenness, automatic behaviors, and memory disturbances.
[36] Solriamfetol is a dopamine and norepinephrine reuptake inhibitor (NDRI) used to treat excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea.
[39] 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.
[41] In July 2020, the FDA approved Xywav™ (calcium, magnesium, potassium, and sodium oxybates), an oral solution for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.
[50] Research findings suggest that the GABA neurotransmitter system plays a significant role in the etiology of primary hypersomnias, such as IH and Narcolepsy Type 2.
[51] Given the possible role of hyperactive GABAA receptors in IH, medications that could counteract this activity are being studied to test their potential to improve sleepiness.
Research has shown that flumazenil provides relief for most patients whose CSF contains the unknown "somnogen" that enhances the function of GABAA receptors, making them more susceptible to the sleep-inducing effect of GABA.
[52] Clarithromycin, an antibiotic approved by the FDA for the treatment of infections, was found to return the function of the GABA system to normal in patients with IH.
[55] The American Academy of Sleep Medicine's 2021 clinical practice guidelines conditionally suggested its use, especially for those who don't respond to other therapies.
[56][57] Dr. Ferini-Strambi and his colleagues in Milan, Italy, performed neurologic examinations by applying anodal tDCS by placing one electrode over the left dorsolateral prefrontal cortex, with the cathode over the contralateral orbit over 3 weeks period and found that seven of the eight participants (87.5%) reported improvement in their daytime sleepiness, including for up to two weeks after the end of the study.
[60] 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.
[62] Selegiline, a monoamine oxidase B (MAO-B) inhibitor, works by slowing the breakdown of certain substances in the brain (mostly dopamine, but also serotonin and norepinephrine).
[20] Atomoxetine is a norepinephrine reuptake inhibitor (NRI) 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.
"[20] Ritanserin is a serotonin antagonist that has "been shown to improve daytime alertness and subjective sleep quality in patients on their usual narcolepsy medications."
Bupropion, a norepinephrine-dopamine reuptake inhibitor (NDRI), which works by inhibiting the reabsorption of two important brain chemicals – norepinephrine and dopamine, is known to have wake-promoting effects.
[citation needed] Fluoxetine, an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class is also known to have mild stimulating effects.
It is widely used but "has intolerable side effects at high doses (including cardiovascular), and it is generally not efficient enough for patients with hypersomnia or narcolepsy.
"Mice with systemic carnitine deficiency exhibit a higher frequency of fragmented wakefulness and rapid eye movement (REM) sleep, and reduced locomotor activity."