Idiopathic hypersomnia …

Nathan A Walker MD

Sleep Disorders

Updated 02.16.2026
Released 10.11.1993
Expires For CME 02.16.2029

Idiopathic hypersomnia

Author: Nathan A Walker MD

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Editor: Bradley V Vaughn MD

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Idiopathic hypersomnia

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Introduction

Overview

Idiopathic hypersomnia is a central disorder of hypersomnia characterized by excessive daytime sleepiness, sleep inertia, and unrefreshing sleep despite adequate quantity and quality of sleep. These patients often have prolonged sleep times of over 11 hours–sometimes 14 or more hours. These patients do not have cataplexy, separating the disorder from narcolepsy type I. The excessive daytime sleepiness is not better explained by another mechanism; hence, it is idiopathic. Because the cause is unknown, treatment is targeted at symptoms.

Key points

	• The main symptom of idiopathic hypersomnia is excessive daytime sleepiness with an urge for more sleep despite adequate, and often prolonged, sleep.
	• Sleep periods are normal, at least 7 hours, and are unrefreshing and accompanied by sleep inertia.
	• Diagnosis is made by clinical history and an overnight polysomnogram with at least 7 hours of sleep to rule out other causes of hypersomnia, followed by an MSLT with a mean sleep latency of less than 8 minutes and less than 2 sleep-onset REM periods (SOREMPS).
	• Symptoms of autonomic dysfunction may be present.
	• Other disorders that can result in hypersomnia must be ruled out, such as insufficient sleep, sleep-disordered breathing, circadian rhythm disorders, and narcolepsy, among others. Symptoms must also not be better explained by a medication effect.
	• Treatment is symptoms based, usually involving stimulants, and education on improving sleep behaviors.

Historical note and terminology

Idiopathic hypersomnia was initially diagnosed as narcolepsy; however, with the advent of polysomnography, the lack of sleep-onset REM periods in these patients was noted. Dement and colleagues suggested another diagnostic category for patients that had excessive daytime sleepiness but lacked cataplexy, sleep paralysis, and sleep-onset REM (18). Different terminology has been used in the past, including essential narcolepsy, non-REM sleep narcolepsy, and idiopathic hypersomnia (06; 48; 53). Also, idiopathic hypersomnia was previously subdivided into two categories: (1) idiopathic hypersomnia and long sleep time, which included an overnight sleep period of over 10 hours with prolonged unrefreshing naps (2) and idiopathic hypersomnia without long sleep time, which included an overnight sleep time of less than 10 hours and unrefreshing naps (02). The International Classification of Sleep Disorders, 3rd edition TR (ICSD 3TR), does not make this distinction (03).

Table 1. Criteria for Idiopathic Hypersomnia

Idiopathic hypersomnia diagnostic criteria (must meet criteria A to F)
	A. The patient has daily periods of irrepressible need to sleep or daytime lapses into drowsiness or sleep occurring for at least 3 months B. Cataplexy is absent C. Polysomnography and multiple sleep latency test (MSLT) findings are not consistent with a diagnosis of narcolepsy type 1 or 2 D. The presence of at least one of the following:
		1. The MSLT, performed in accordance with current recommended protocols, shows a mean sleep latency of ≤ 8 minutes
		2. Total 24-hour sleep time is ≥ 660 minutes (typically 12 to 14 hours) on 24-hour polysomnographic monitoring (performed after correction of chronic sleep deprivation), or by wrist actigraphy in association with a sleep log (averaged over at least 7 days with unrestricted sleep)
	E. Insufficient sleep syndrome is ruled out (if deemed necessary, by lack of improvement of sleepiness after an adequate trial of increased nocturnal time in bed, preferably confirmed by at least one week of wrist actigraphy) F. The symptoms and signs are not better explained by a circadian rhythm sleep-wake disorder, or other current sleep disorder, mental disorder, or medication/substance use or withdrawal
Relevant notes
	• Severe and prolonged sleep inertia (sleep drunkenness) • Total 24-hour sleep time required for diagnosis is adapted based on normal changes in sleep duration for development (children, adolescents) and cultural variance.
Adapted from (03).

Clinical manifestations

Presentation and course

	• Patients with idiopathic hypersomnia have excessive daytime sleepiness despite frequently prolonged and undisturbed primary sleep periods with high sleep efficiency.
	• Despite the prolonged sleep periods, many patients will take naps that are often prolonged and unrefreshing.
	• Most patients with idiopathic hypersomnia suffer from sleep inertia on waking.
	• Symptoms of autonomic dysfunction may occur in individuals with idiopathic hypersomnia.

Onset of symptoms of idiopathic hypersomnia typically occurs in adolescence and early adulthood. The key feature is near constant excessive daytime sleepiness and a sense of never feeling alert. According to the Hypersomnia Foundation Registry study, 97% of individuals with sleep periods of under 10 hours experienced excessive daytime sleepiness, and 98% of those with sleep periods of over 10 hours experienced excessive daytime sleepiness (70). A key distinction between idiopathic hypersomnia and narcolepsy type I is a lack of cataplexy in idiopathic hypersomnia. In addition to long nocturnal sleep, patients with idiopathic hypersomnia often report prolonged naps during the day; 64.2% of idiopathic hypersomnia patients with long sleep times reported napping an average of 2.8 hours, whereas 42.1% of those with normal sleep times reported naps of roughly 2 hours (70). Most patients with idiopathic hypersomnia report unrefreshing naps as opposed to narcolepsy patients, whose naps are usually brief and refreshing. However, in one study, only 37% of patients with narcolepsy type II reported refreshing sleep.

The nighttime sleep period is often prolonged in patients with idiopathic hypersomnia. Roughly 50% of patients with idiopathic hypersomnia have primary sleep periods of over 10 hours (21). In contrast to patients with narcolepsy, nighttime sleep in patients with idiopathic hypersomnia is much less fragmented (36). Nocturnal sleep is highly consolidated with high sleep efficiencies of over 85% and often over 90%. Macroarchitecture shows increased REM sleep and lower narcolepsy type III sleep (36; 49). Wake from sleep is difficult for patients with idiopathic hypersomnia. This is called “sleep inertia,” also referred to as “sleep drunkenness” in the literature. Patients may report the use of multiple or sophisticated alarms in an attempt to help wake them from sleep. Roughly 79% of patients with idiopathic hypersomnia report suffering from sleep inertia (70). Sleep inertia is not required for the diagnosis of idiopathic hypersomnia as up to 55% of patients with narcolepsy type II report this as well (21). On awakening, patients with idiopathic hypersomnia may have automatic behaviors, disorientation or confusion, and poor coordination. This may last minutes to hours and may account for the common complaint of brain fog (09). Over 80% of patients with idiopathic hypersomnia report brain fog (70). Brain fog encompasses many symptoms, including difficulty concentrating, slowed thinking, memory lapses, and communication difficulties (52). Compared to healthy controls, one study found a higher prevalence of memory problems (79% vs. 43%), attention deficit (55% vs. 18%), and frequent forgetfulness (47% vs. 5%), respectively (73).

There is an association with autonomic dysfunction in idiopathic hypersomnia. The prevalence of autonomic dysfunction is not known in adult idiopathic hypersomnia patients but frequently manifests as orthostatic hypotension, vasomotor, gastrointestinal, and bladder symptoms (40). There is also an association with mental health disorders in idiopathic hypersomnia, including anxiety and depression (63).

The symptoms of idiopathic hypersomnia create a high quality-of-life burden. Patients with idiopathic hypersomnia are at greater risk for the development of moderate to severe depression (51). Symptoms of brain fog, sleep inertia, and decreased alertness result in missed work and impairment when at work (63). Often patients with idiopathic hypersomnia are excluded from holding certain jobs as well. Social relationships are also reported as suffering due to the symptoms and a sense of stigmatization due to the illness (63).

Prognosis and complications

Idiopathic hypersomnia is considered a chronic life-long disorder with little change over time. However, spontaneous remission has been reported in 14% to 33% of patients in clinical studies (12). An analysis of patients in the Hypersomnia Foundation Registry showed relatively stable symptoms over time. Although there was no worsening of symptoms over time, many of the more debilitating symptoms remained constant despite treatment. There was a slight change in the reported difficulty in awakening in the morning, reducing from 78.7% to 73% (12). The major complications of idiopathic hypersomnia remain related to the impairment in functioning, with major quality-of-life impacts on work, social, and professional duties (70; 63). Falling asleep while driving or impaired driving caused by fatigue or sleepiness pose the greatest mortality risk (03).

Clinical vignette

A 20-year-old woman presented to a clinic with a several-year history of excessive daytime sleepiness starting in high school. She reported difficulty waking for classes in high school and would frequently require her parents to wake her as she would sleep through her alarm. She reported difficulty concentrating in class and would feel the need to sleep throughout the day. She also described frequently taking naps lasting an hour or more and waking from these feeling unrefreshed. Her symptoms continued in college regardless of how much sleep she got. She reported getting 10 hours of sleep during the school week but would often sleep 12 to 14 hours on weekends. Even with increased sleep on the weekends, she reported difficulty waking and required multiple alarms to wake her. She often missed her morning classes due to sleeping through her multiple alarms. She denied disrupted sleep and kept to a regular sleep schedule. She denied any snoring, witnessed apneas, cataplexy, restless legs, hypnic hallucinations, or sleep paralysis. She took no medications but frequently drank coffee and energy drinks in an effort to help her stay alert, with little reported effect. Review of systems and family history was unrevealing. Her exam was unremarkable with a normal BMI and no neurologic deficits noted on exam. Recent lab work showed normal values for electrolytes and renal, liver, and thyroid function, as well as a normal A1C.

Workup consisted of 2-week actigraphy followed by an overnight polysomnography and next day multiple sleep latency test (MSLT). Actigraphy showed an average sleep time of 11 hours with a maximum sleep time of 16 hours. Her polysomnography showed a sleep latency of 7 minutes with high sleep efficiency of 95%. She slept 14 hours in the overnight polysomnography. The patient did not meet criteria for sleep apnea nor periodic limb movements of sleep. Her MSLT was remarkable for a mean sleep latency of less than 5 minutes and no sleep-onset REM periods.

She was diagnosed with idiopathic hypersomnia. Due to living in a dorm, she was started on modafinil 100 mg in the morning and another 100 mg in the early afternoon. She had modest improvement in her daytime sleepiness but continued to have difficulty with sleep inertia. When she moved out of her dorm and into an apartment by herself, she was switched to low sodium oxybate and titrated to a dose of 3 grams twice nightly. This resulted in increased improvement in her daytime sleepiness as well as sleep inertia, and she was able to graduate from college and obtain employment in her chosen field.

Biological basis

• As the name implies, the cause of idiopathic hypersomnia is unknown.

Etiology and pathogenesis

The etiology of idiopathic hypersomnia is unknown. There are no current animal models to allow for further elucidation. There have been several studies in the previous decades implying the role of various genes, neurotransmitters, and pathways, but none have been conclusive.

Clusters of idiopathic hypersomnia have been reported in families; as high as 30% of patients note a familial predisposition. A genetic basis has been proposed; however, genome-wide association studies have not found any strong gene associations (66). The circadian gene PER3 has been implicated as having a high association in patients with idiopathic hypersomnia (13). Expression of the clock genes BMAL1 and PER1/2 has also been shown to be dampened in patients with idiopathic hypersomnia, implicating a possible role of circadian regulation of sleep promotion during wake periods (33).

Reduced activity in the prefontal cortex, by way of cerebral blood flow, has been shown in patients with idiopathic hypersomnia. Reduction in blood flow in this area of the brain has been correlated with objective and subjective findings of pathologic sleepiness (08). Many neurotransmitters have been implicated in the pathogenesis of idiopathic hypersomnia due to the effectiveness in reducing excessive daytime sleepiness in patients with idiopathic hypersomnia by increasing their activity. CSF orexin concentrations in patients with idiopathic hypersomnia are normal. Neurochemical analysis of CSF monoamine metabolites has not consistently documented differences from controls; however, changes in dopamine, norepinephrine, and histamine signaling have all been implicated as possible pathways of pathogenesis. Modafinil, which increases dopamine and acts on several other neurotransmitter receptors, has been shown to reduce excessive daytime sleepiness in idiopathic hypersomnia (39). Two medications, pitolisant and solriamfetol, have been studied for use in narcolepsy and are also effective in treating the excessive daytime sleepiness of that disorder, suggesting the role of histamine and norepinephrine in the pathogenesis (68).

Differential diagnosis

Confusing conditions

Idiopathic hypersomnia is a diagnosis of exclusion. Diagnostic difficulties arise because there are numerous conditions and disorders that can produce excessive daytime sleepiness. In addition, many of these conditions can and do coexist in patients with a central disorder of hypersomnolence, such as idiopathic hypersomnia. Therefore, many factors need to be considered in the differential diagnosis of a patient with possible idiopathic hypersomnia (44).

The most common feature that may be confused with idiopathic hypersomnia is insufficient sleep syndrome. According to a CDC report, an estimated 33% of adults reported short sleep (< 7 hours in a 24-hour period) (47). Clinicians must astutely delineate the total hours dedicated to sleep and compare this to the patient’s inherent sleep need. This is especially important for individuals who may require sleep periods longer than 8 or 9 hours. Therefore, attaining 7 to 8 hours is insufficient for these individuals, producing sleep deprivation despite meeting the “average” or “acceptable” time dedicated to sleep. Careful measures, including actigraphy and sleep diaries, may provide clues, and improvement in symptoms with true sleep extension may help identify this disorder.

In a study by Bixler and colleagues, being treated for depression was the most significant risk factor for having a complaint of excessive daytime sleepiness (07). This was a stronger correlation than BMI, age, estimates of sleep duration, diabetes, smoking, and sleep apnea. Therefore, concomitant disorders that may also have excessive daytime sleepiness must be explored and corrected before a diagnosis of idiopathic hypersomnia can be made (03). Excessive daytime sleepiness associated with depression is often distinguishable from idiopathic hypersomnia based on later onset in life and a history of chronic depression. Laboratory testing in patients with excessive daytime sleepiness from depression often demonstrates a normal sleep time on the overnight polysomnography with normal sleep latency times on MSLT (19). Mood symptoms often do not improve with treatment of the hypersomnia (23). Comorbid anxiety and depression have been reported to present in over 40% of patients with idiopathic hypersomnia (12). In addition, patients with idiopathic hypersomnia often develop depression after the initial symptom onset, and attention should be paid to treating both mood and hypersomnia disease (17; 73).

Sleep disorders that result in excessive daytime sleepiness should also be ruled out. These conditions usually impair the quality or quantity of sleep at night. Sleep-disordered breathing, restless legs syndrome, periodic limb movement disorder, and circadian rhythm sleep-wake disorders are common causes of disrupted sleep and can result in daytime sleepiness. A sleep-related breathing disorder, upper airway resistance syndrome (UARS), was formerly recognized as a separate entity and could also result in excessive daytime sleepiness. However, this disorder has been subsumed under obstructive sleep apnea as the pathophysiology is felt to be the same. It was formerly based on the respiratory disturbance index (RDI), which includes apneas, hypopneas, and respiratory event–related arousals with an RDI greater than or equal to five events per hour with apnea hypopnea index (AHI) less than five. The ICSD 3TR classifies obstructive sleep apnea as having an RDI or AHI greater than five and symptomatic, or an RDI/AHI greater than or equal to 15 (03). Lastly, patients with circadian rhythm disorders, particularly delayed sleep phase syndrome, often complain of excessive daytime sleepiness and difficulty waking in the morning. However, these patients usually feel awake at night and often go to bed very late (74). Sleep diaries or actigraphy can help with this diagnosis.

Idiopathic hypersomnia must be distinguished from other central disorders of hypersomnolence. This includes narcolepsy type I and II as well as Kleine-Levine syndrome. Narcolepsy type I can be distinguished from idiopathic hypersomnia by the presence of cataplexy (56). Narcolepsy type I can also be diagnosed by decreased orexin concentrations in cerebral spinal fluid. Differentiating idiopathic hypersomnia from narcolepsy type II can be more difficult due to lack of cataplexy and normal orexin levels and similar clinical symptoms (61). Kleine-Levin syndrome is a rare central disorder of hypersomnia characterized by recurrent episodes of excessive daytime sleepiness associated with psychiatric symptoms. The episodes usually last a week to 10 days but can last longer. Notably, patients are at their normal baseline between episodes. Onset is usually in the second decade with slow remission over the lifespan (03).

Numerous other medical and neurologic disorders can present with symptoms of excessive daytime sleepiness. Excessive daytime sleepiness is a common complaint in Parkinson disease and can be seen in the other alpha-synucleinopathies. Hypersomnia can be a complaint after stroke or traumatic brain injury. Patients suffering from renal or hepatic insufficiency can have excessive sleepiness as well (15; 35; 03). Chronic fatigue syndrome may be mistaken for idiopathic hypersomnia due to the lack of symptoms resolution despite prolonged bed rest. However, sleepiness, defined as the propensity to sleep, should be distinguished from fatigue, which is more a lack of energy (27).

There are multiple substances that can result in excessive daytime sleepiness as a side effect of taking the substance or as a result of withdrawal. Sedating substances include alcohol, opiates, barbiturates, marijuana, benzodiazepines, benzodiazepine receptor agonists, antiseizure medications, antipsychotics, antihistamines, and antidepressants (22). Withdrawal from stimulating substances can also result in hypersomnia. This can be seen in withdrawal from stimulants, such as amphetamines or even caffeine. A thorough history should help the astute clinician distinguish substance-induced hypersomnia from idiopathic hypersomnia.

Associated or underlying disorders

Symptoms of autonomic dysfunction may be present in patients with idiopathic hypersomnia. The most common complaints are similar to Raynaud phenomenon, orthostatic hypotension, temperature intolerance, heart palpitations, and constipation or diarrhea (73). The prevalence of these symptoms is higher in patients with idiopathic hypersomnia than in the general population. The most common disorder is postural orthostatic tachycardia syndrome (POTS), which was found in 13% of patients with idiopathic hypersomnia as compared to 7% in the general population (40). The severity of hypersomnia has also been associated with increased severity of autonomic symptoms and decreased quality of life (40). The underlying mechanism for the relationship is unknown.

Diagnostic workup

	• Idiopathic hypersomnia is a diagnosis of exclusion, and other disorders that cause daytime sleepiness and fatigue need to be ruled out first.
	• There is no currently approved diagnostic blood or CSF test or procedure to assess for idiopathic hypersomnia.
	• Objective measures to verify the diagnosis of idiopathic hypersomnia include a mean sleep latency of less than 8 minutes, over 660 minutes of sleep demonstrated on an extended 24-hour polysomnography, or an average nightly sleep duration of more than 660 minutes as captured on actigraphy and sleep diaries. Yet these procedures can make the diagnosis only after the exclusion of other disorders.

Idiopathic hypersomnia is diagnosed based on a clinical history, with polysomnography, MSLT, and actigraphy performed to confirm the diagnosis and rule out other sleep disorders.

Diagnosing idiopathic hypersomnia begins with a clinical history consistent with the symptoms and presentation previously mentioned. The history can be supplemented with questionnaires to help establish the severity of the patient’s symptoms. The Epworth Sleepiness Scale (ESS) is widely used, with a cutoff of 10 points defining excessive daytime sleepiness (26). A more recent questionnaire, the Idiopathic Hypersomnia Severity Scale (IHSS), was developed to capture more symptoms than just excessive daytime sleepiness. The IHSS also captures daytime functioning, sleep duration and inertia, as well as napping, in addition to daytime sleepiness (16). The IHSS is also a Likert scale like the ESS, with scores for each component ranging from 0 to 4 and a cutoff score of 22 differentiating idiopathic hypersomnia from controls. A cutoff score of 26 has been established as differentiating treated versus untreated patients with idiopathic hypersomnia as well (16; 51).

The most common objective testing used to confirm the diagnosis of idiopathic hypersomnia is an overnight polysomnography with next day MSLT. The polysomnography allows for the ruling out of other sleep disorders, such as obstructive sleep apnea, periodic limb movement disorder, and fragmented sleep, as a cause of excessive daytime sleepiness. The combination of polysomnography and next day MSLT allows for distinguishing idiopathic hypersomnia from narcolepsy. However, care should be taken during these tests not to wake the patient before their normal wake time and to let them sleep in as long as they like. Waking a patient prior to their normal REM sleep-onset times can confound the diagnosis by iatrogenically inserting REM sleep into the naps on the MSLT, resulting in a false positive diagnosis of narcolepsy. This is particularly of concern in patients with a delayed circadian sleep disorder.

Carskadon and Dement originally designed the MSLT to diagnose narcolepsy (10). However, the MSLT is more limited outside this disorder (41; 72). Nevertheless, the MSLT is used to help confirm the diagnosis of idiopathic hypersomnia despite 40% of patients with idiopathic hypersomnia having a mean sleep latency of over 8 minutes and 10% to 25% of the general public having a mean sleep latency of under 8 minutes (20; 03). In addition, repeat MSLT has shown normal sleep latencies in 75% of patients previously diagnosed with idiopathic hypersomnia with MSLT (34).

A newer allowed objective test is the use of prolonged, ie, 24-hour, polysomnography to assess for sleep longer than 660 minutes (03). Prolonged polysomnography typically captures extended nighttime sleep and prolonged naps during the day. Meta-analyses of these polysomnographies in patients with idiopathic hypersomnia have shown decreased slow-wave sleep, increased REM sleep, greater total sleep time, and shorter sleep-onset latency as compared to controls (49). In comparison to patients with narcolepsy type I, prolonged polysomnography has shown less wake after sleep onset, arousals, total narcolepsy type I sleep, and limb movements and greater sleep efficiency in patients with idiopathic hypersomnia. There are fewer differences in prolonged polysomnography parameters in patients with idiopathic hypersomnia versus narcolepsy type II, with the exception of higher REM sleep percentage and shorter REM sleep-onset latency in patients with narcolepsy type II (75). An alternative to polysomnography is the use of actigraphy showing an average of at least 11 hours of sleep time over 7 days (03).

Testing for the status of HLA-DQB1*0602 is not recommended as it is neither sensitive nor specific for diagnosis in idiopathic hypersomnia. The presence of this haplotype in patients with narcolepsy type II is reported to be 40% to 50%. It is also found in 12% to 38% of the population at large (32; 42; 04). Imaging studies, such as CT or MRI of the brain, are not typically used unless there is suspicion for an underlying neurologic lesion based on history and physical exam (69).

If a mood disorder is suspected, then a psychiatric evaluation may be necessary. Coexisting mood disorders are common in patients with idiopathic hypersomnia but may need to be fully treated before making the diagnosis of idiopathic hypersomnia. In addition, laboratory work for thyroid function, iron status, complete blood count, and vitamin B12, among others, may be necessary to rule out medical conditions that may also cause excessive daytime sleepiness.

Management

	• Because the cause of idiopathic hypersomnia is unknown, symptomatic treatment of excessive daytime sleepiness is the main therapeutic approach.
	• Low sodium oxybate is the only FDA-approved treatment for idiopathic hypersomnia.
	• Stimulant medication, such as modafinil and amphetamines, and newer medications, such as pitolisant and solriamfetol, are often used off label for the treatment of idiopathic hypersomnia.
	• Patients with idiopathic hypersomnia have a variable response rate to treatment, likely reflecting the complex and unknown etiology of the disorder.
	• Randomized controlled trials studying medications in idiopathic hypersomnia are few, and there is currently one FDA-approved medication for idiopathic hypersomnia.

Treatment of idiopathic hypersomnia is mainly targeted at improving the symptom of excessive daytime sleepiness. However, there is less evidence to support the various medications employed (37; 38). The FDA has approved only one medication, low-sodium oxybate, for the treatment of idiopathic hypersomnia due to improvement in ESS, IHSS, and global impression of change scores found in a double-blind placebo-controlled randomized controlled trial (14). Other medications used for the treatment of idiopathic hypersomnia are used off-label.

Lifestyle modifications in the form of sleep hygiene and scheduled naps can also complement treatment with medication (01). A small number of patients with idiopathic hypersomnia had some improvement in a study of cognitive behavioral therapy for hypersomnia, with demonstrated improvement in ESS (45). Patients with idiopathic hypersomnia should also be educated about the impact of the disorder on their social and professional lives to make these patients better equipped to have a more normal life.

The only FDA-approved medication for the treatment of idiopathic hypersomnia is low-sodium oxybate, a formulation of sodium oxybate that works agonistically at the gamma-hydroxybutyrate and GABAb receptors. Sodium oxybate was studied in a population of patients with idiopathic hypersomnia and showed a good response in 65% of 39 patients (29). Low-sodium oxybate was studied in a double-blind, placebo-controlled randomized withdrawal study in patients with idiopathic hypersomnia (14). ESS and IHSS showed statistically significant improvements from baseline with the medication as well as clinically meaningful worsening in symptoms following withdrawal. ESS worsened by 6.5 points by least squares mean (95% CI: 5.0–8.0; p< 0.0001) in the placebo withdrawal group as compared to those still taking low-sodium oxybate. The mean change in IHSS was 12 points worse (95% CI: 8.0–15.0; p< 0.0001). These findings were consistent across subgroup analysis; long sleep time versus normal sleep time and side effect profiles were similar to the use of other oxybates.

Modafinil and its enantiomer armodafinil have been shown to have a similar benefit in idiopathic hypersomnia as that seen in narcolepsy type I (05; 28). In a randomized controlled trial, Inoue and colleagues showed increases in mean sleep latency on a maintenance of wakefulness test as well as decreases in ESS in the group on modafinil as compared to placebo (24).

Additional therapies have also been employed, including the antibiotic clarithromycin, which may be a GABAa receptor inhibitor. In a randomized controlled trial, patients were randomized to placebo or 500 mg of clarithromycin twice daily (71). There was no difference between groups on the primary endpoint of improvement on a psychomotor vigilance task (PVT); however, participants receiving the antibiotic showed improvement in the Stanford Sleepiness Score and Functional Outcomes of Sleep Questionnaire. Flumazenil has also been studied in idiopathic hypersomnia as a benzodiazepine receptor antagonist, with minor improvement in PVT outcome and subjective alertness (54). Pitolisant, an inverse histamine agonist, has also been studied in idiopathic hypersomnia as well as narcolepsy with significant improvement in excessive daytime sleepiness (30; 65). Solriamfetol, an FDA-approved therapy for excessive daytime sleepiness, has also been suggested as a possible therapy for idiopathic hypersomnia, yet evidence is limited for this medication in this population (57).

Due to the variable response rates of first-line treatments, many patients are tried on a combination of medications or a trial of alternate therapies (67). In a longitudinal study of patients in the Hypersomnia Foundation Registry, 44.6% of patients made one or more medication changes over the course of the study (12).

Outcomes

Even when treated, patients with idiopathic hypersomnia often continue to report excessive daytime sleepiness, sleep inertia, and requiring multiple alarms to wake; however, subjective patient-reported outcomes are usually favorable. In a study of the Hypersomnia Foundation Registry, 64.1% continued to report excessive daytime sleepiness, 60.2% still required multiple alarms, and 61.1% continued to have sleep inertia. Brain fog and memory impairment were reported in over 50% of patients (70). From a quality-of-life standpoint, patients continue to suffer impairment in work and their social life, with reduced scores in assessments of general health (17; 46; 70; 58).

Complications of treatment are specific to the action of the medications. Modafinil is usually better tolerated than amphetamines, which increase the release of dopamine and norepinephrine. However, there is reported risk of Stevens-Johnson syndrome with modafinil, and this medication can reduce the efficacy of hormonal contraception therapy (11). Amphetamine stimulants are more likely to raise blood pressure and heart rate through their increased sympathetic activity. In addition, this class of medication is more likely to be abused and can worsen hypersomnia in withdrawal (64; 31; 43). Lower-sodium oxybate has a risk of causing worsened anxiety and depression along with suicidal ideation. This medication also has a black box warning for CNS and respiratory depression and has risk for abuse or misuse. To prescribe this medication, both the patient and the prescriber must be enrolled in the risk and mitigation strategy (REMS) program, and this medication is only distributed from a single pharmacy in the United States (25).

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All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Nathan A Walker MD

Dr. Walker of UNC Chapel Hill School of Medicine has no relevant financial relationships to disclose.
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Editor

Bradley V Vaughn MD

Dr. Vaughn of UNC Hospital Chapel Hill and University of North Carolina School of Medicine has no relevant financial relationships to disclose.
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Former Authors

Michael Billiard MD
Michael S Aldrich MD
Stephen H Sheldon DO
Harold R Smith MD
Marcel Hungs MD PhD
Saba Ahmad MD
Pallavi P Patwari MD
Michael J Howell MD
Logan Schneider MD

Patient Profile

Age range of presentation: 13 to 44 years
Sex preponderance: female>male
Heredity: Heredity may be a factor, but unknown
Population groups selectively affected: No population group selectively affected
Occupation groups selectively affected: No occupation group selectively affected

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Idiopathic hypersomnia

Associated Disorders

postural orthostatic tachycardia syndrome

Differential Diagnosis

insufficient sleep syndrome
depression
sleep-disordered breathing
restless legs syndrome
periodic limb movement disorder
- circadian rhythm sleep wake disorders
- obstructive sleep apnea
- narcolepsy type I
- narcolepsy type II
- Kleine-Levine syndrome
- Parkinson disease
- alpha-synucleinopathies
- stroke
- traumatic brain injury
- renal or hepatic insufficiency
- chronic fatigue syndrome
- substance-induced hypersomnia

Also Relevant

Hypersomnolence
Modafinil
Narcolepsy
Obstructive Sleep Apnea
Posttraumatic sleep disturbance
- Recurrent hypersomnia
- Sleep disorders

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Sleep Disorders

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Web References

Testing

Narcolepsy Risk Factor

Clinical Trials

NIH: Sleep Disorders

	• The prevalence of idiopathic hypersomnia is estimated at 0.01% in the U.S. population.
	• Women are more affected than men.

Idiopathic hypersomnia

Cite this article

Introduction

Overview

Key points

Historical note and terminology

Table 1. Criteria for Idiopathic Hypersomnia

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

References

Contributors

Author

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Patient Profile

ICD & OMIM codes

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