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Idiopathic hypersomnia

Idiopathic hypersomnia
Author:
Ronald D Chervin, MD, MS
Section Editor:
Thomas E Scammell, MD
Deputy Editor:
April F Eichler, MD, MPH
Literature review current through: Feb 2022. | This topic last updated: Jan 31, 2022.

INTRODUCTION — Idiopathic hypersomnia is a sleep disorder that is characterized by chronic excessive daytime sleepiness (daily periods of irrepressible need to sleep or daytime lapses into sleep) and often difficulty waking up from nocturnal sleep or daytime naps. The condition is categorized as a central disorder of hypersomnolence; other sleep disorders in this category include narcolepsy type 1 and type 2 and Kleine-Levin syndrome (recurrent hypersomnia) [1].

The pathophysiology of idiopathic hypersomnia is not well understood, and diagnosis requires exclusion of other more common causes of excessive sleepiness. When a diagnosis of idiopathic hypersomnia is established, treatment is largely pharmacologic and aimed at control of symptoms, with generally good, but somewhat variable results.

This topic will discuss the epidemiology, clinical features, diagnosis, and treatment of idiopathic hypersomnia. An approach to the patient with excessive daytime sleepiness is presented separately. (See "Approach to the patient with excessive daytime sleepiness".)

EPIDEMIOLOGY — The prevalence of idiopathic hypersomnia in the general population is unknown [2], in part because laboratory-based polysomnography and other assessments that would be necessary to rule out other causes of excessive daytime sleepiness have not been feasible in large numbers of unselected, representative subjects from the community. Based largely on sleep center referrals, idiopathic hypersomnia appears to be one-tenth to one-half as common as narcolepsy, suggesting a prevalence of approximately 20 to 50 cases per million [3-6]. Males and females are equally affected.

The onset of idiopathic hypersomnia typically occurs between 10 and 30 years of age. In a series of 77 patients, the mean age of symptom onset was 17 and the mean age of diagnosis was 30 [3].

PATHOGENESIS — The pathogenesis of idiopathic hypersomnia is not well understood [7]. Some cases may be precipitated by a viral illness [8], suggesting a possible autoimmune etiology. Reports of distinctive HLA markers have been inconsistent [9]. A series of 138 patients with idiopathic hypersomnia found that the prevalence of inflammatory disorders, allergies, and family members with inflammatory disorders was increased in patients compared with controls [10].

One small study suggested that an endogenous substance in the cerebrospinal fluid of some patients with primary hypersomnias, including idiopathic hypersomnia, may enhance inhibitory signaling through gamma-aminobutyric acid type A (GABAA) receptors, thereby promoting sleepiness; the effects were reversed in vitro by flumazenil, which also normalized vigilance in seven patients [11]. A pilot study from the same group found that clarithromycin improved subjective sleepiness without improving objective signs of alertness in patients with evidence of abnormal GABAA potentiation [12]. In contrast, a separate study could not confirm in vitro GABAA potentiation with cerebrospinal fluid from 15 patients with idiopathic hypersomnia [13]. Nonetheless, limited data suggest that flumazenil may be beneficial in some patients. (See 'Pharmacotherapy' below.)

Disruption of the default-mode network may play a role in the symptoms of idiopathic hypersomnolence. This was suggested by a magnetic resonance imaging (MRI) study of 12 patients with idiopathic hypersomnia and 15 controls, which found localized differences in brain volume and cortical thickness as well as resting functional connectivity [14]. The latter correlated with subjective daytime sleepiness.

Hypocretin-1, the wake-promoting neurotransmitter found to be absent or deficient in patients with narcolepsy type 1, is normal in idiopathic hypersomnia [15,16]. Standard cerebral spinal fluid tests are normal, although one study found altered dopamine and indoleacetic acid levels [17] and another suggested dysregulation of norepinephrine [18]. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Orexin/hypocretin'.)

A familial tendency can be seen in as many as half the subjects, with both idiopathic hypersomnia and narcolepsy being reported in other family members. Some familial patterns suggest an autosomal dominant mode of inheritance.

CLINICAL PRESENTATION — The typical patient with idiopathic hypersomnia is an adolescent or young adult who complains of chronic and disabling excessive daytime sleepiness (EDS). Affected patients are unable to maintain wakefulness and alertness during the major waking episodes of the day, with sleep occurring unintentionally or at inappropriate times and interfering with function. The onset of EDS is often insidious, developing over several weeks to months. Scores on subjective assessments of EDS such as the Epworth Sleepiness Scale (calculator 1) are abnormally high (10 or higher). (See "Quantifying sleepiness", section on 'Epworth Sleepiness Scale (ESS)'.)

Daytime sleepiness leads to naps that tend to be long (an hour or more) and unrefreshing, in contrast to the experience reported in narcolepsy. Many patients take naps on five or more days per week. Also unlike patients with narcolepsy, patients with idiopathic hypersomnia do not generally have sleep attacks (instances of irresistible sleep). (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Daytime sleepiness'.)

Total 24-hour sleep time and nocturnal sleep time are often, but not always, prolonged in patients with idiopathic hypersomnia. The 24-hour sleep duration is often 12 to 14 hours. Sleeping longer at night does not appear to improve the EDS. Some argue that idiopathic hypersomnia with and without long sleep time should be distinguished as separate diagnostic entities. When 44 patients with idiopathic hypersomnia were carefully characterized based on demographic and clinical features, those with long sleep (>10 hours at night, or >11 hours in a 24-hour period) were often female, were on average younger at disease onset, had longer mean sleep latency values on multiple sleep latency tests, and for the most part found daily naps to be unrefreshing [19]. Moreover, idiopathic hypersomnia patients with long sleep duration showed more severe sleep inertia, fatigue, and evening chronotype.

Another common feature of idiopathic hypersomnia can be difficulty arousing from nocturnal sleep periods or daytime naps. Patients often report transient periods of confusion and "sleep drunkenness" upon awakening. Other features that are common but nonspecific in patients with hypersomnolence include automatic behaviors during wakefulness, sleep paralysis (complete inability to move for several minutes upon awakening), and hypnagogic hallucinations (vivid visual, tactile, or auditory dream-like experiences that occur as the patient is falling asleep) [20]. In a prospective study of 75 patients referred to a sleep disorders unit for EDS and who met diagnostic criteria for idiopathic hypersomnia, sleep drunkenness was reported by 36 percent of patients, sleep paralysis by 28 percent, and hypnagogic hallucinations by 24 percent [21].

Consequences of excessive daytime sleepiness in patients with idiopathic hypersomnia resemble those seen in patients with sleepiness from other causes. Work productivity, relationships, family obligations, enjoyment of free time, driving, and safety can all be affected. Idiopathic hypersomnia can be associated with depression as well as nonspecific neurological symptoms such as headache, lightheadedness, orthostatic hypotension, or syncope.

A 14-item Idiopathic Hypersomnia Severity Scale (IHSS) has been developed based on self-reported symptoms and consequences [22]. Data to support its validity and reliability suggest it may be useful to quantify or follow symptoms and distinguish patients with idiopathic hypersomnia from patients with narcolepsy. The instrument takes about five minutes to complete.

DIAGNOSTIC EVALUATION — Idiopathic hypersomnia is a clinical diagnosis that should be considered in a teenager or adult who complains of chronic excessive daytime sleepiness (EDS) with long unrefreshing daytime naps and difficulty arousing from sleep, in the absence of symptoms suggestive of other common causes of EDS such as insufficient sleep, depression, sedating medications, and sleep-related breathing disorders. Idiopathic hypersomnia is in part a diagnosis of exclusion that is achieved by a thorough history and polysomnography to ensure that other causes of EDS are not present.

If concern exists about the accuracy of patient-reported sleep duration, a sleep log (table 1 and table 2) or an activity monitor (actigraphy) should be used for confirmation. Actigraphy allows for multiday recording in the home environment and thus can corroborate the history and provide data that supplements in-laboratory sleep testing. Although a study of 33 patients with idiopathic hypersomnia found good correlation between total sleep time as measured by actigraphy and polysomnography [23], clinicians should be aware that the actigraphy software settings used to score wake and sleep can affect accuracy [24]. (See "Actigraphy in the evaluation of sleep disorders".)

This evaluation should distinguish EDS from other common complaints such as fatigue and low energy, which may trigger evaluation for other primary causes. The medication list should be reviewed for drugs that can cause EDS (table 3) and patients should be screened for depression. (See "Approach to the patient with excessive daytime sleepiness", section on 'Initial evaluation' and "Excessive daytime sleepiness due to medical disorders and medications".)

Other tests, such as cerebrospinal fluid analysis, HLA testing, and quantification of hypocretin levels, are not usually necessary and do not reliably contribute to the diagnostic evaluation. They may be sought on occasion to help confirm the presence of narcolepsy type 1, as opposed to idiopathic hypersomnia. Hypocretin levels are primarily a research tool, however, and clinical testing is not currently available in the United States. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Diagnostic evaluation'.)

Polysomnography — Patients should undergo nocturnal polysomnography to exclude other causes of EDS and especially subtle forms of obstructive sleep apnea (OSA) [25,26]. (See 'Differential diagnosis' below.)

In idiopathic hypersomnia, polysomnography may show a short sleep latency, increased total sleep time, increased sleep spindles, and variable changes in sleep efficiency and sleep stage distribution [3,4,21,27,28]. While these findings are supportive of a diagnosis of idiopathic hypersomnia, they are not specific for the diagnosis.

The polysomnogram may provide evidence of other sleep disorders, effectively precluding a diagnosis of idiopathic hypersomnia. As examples:

In OSA, polysomnography shows increased numbers of obstructive apneas, hypopneas, and respiratory effort-related arousals. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on 'Diagnosis'.)

In central sleep apnea, polysomnography shows increased numbers of central apneas, hypopneas, and associated arousals. (See "Central sleep apnea: Risk factors, clinical presentation, and diagnosis", section on 'Diagnostic criteria'.)

In narcolepsy, polysomnography may demonstrate spontaneous awakenings, mildly reduced sleep efficiency, and rapid eye movement sleep within 15 minutes of the onset of sleep, though these findings are not specific or diagnostic for narcolepsy. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Diagnostic evaluation'.)

Multiple sleep latency test — On the day after the duration and quality of nocturnal sleep have been characterized by nocturnal polysomnography, the patient should undergo a multiple sleep latency test (MSLT). This is a series of five daytime nap opportunities that together allow objective characterization of the patient's level of daytime sleepiness, or physiological sleep tendency, as reflected by the mean sleep latency [29]. Care must be taken to perform the MSLT under optimal conditions that are conducive for sleep. In addition, patients must have had sufficient sleep on the night prior to the MSLT for results to be valid and reliable. (See "Quantifying sleepiness", section on 'Multiple sleep latency test (MSLT)'.)

In idiopathic hypersomnia, the mean sleep latency is shortened, generally less than eight minutes [3], and the number of sleep-onset rapid eye movement sleep periods (SOREMPs) is less than two. This result is important because two or more SOREMPs (or one with an additional SOREMP on the preceding nocturnal polysomnogram) suggest a diagnosis of narcolepsy. However, clinicians should keep in mind that the mean sleep latency and number of SOREMPs can vary with repeat testing, in a manner that makes the MSLT-based distinction between narcolepsy type 2 and idiopathic hypersomnia less reliable than would be ideal [30,31].

DIAGNOSTIC CRITERIA — According to the International Classification of Sleep Disorders, a diagnosis of idiopathic hypersomnia requires all of the following [1]:

Daily periods of irrepressible need to sleep or daytime lapses into sleep for at least three months

Cataplexy is absent

A multiple sleep latency test (MSLT) documents fewer than two sleep-onset rapid eye movement periods (SOREMPs), or no SOREMPs if the REM sleep latency on the preceding polysomnogram was ≤15 minutes (see 'Multiple sleep latency test' above)

The presence of at least one of the following:

MSLT shows a mean sleep latency of ≤8 minutes

Total 24-hour sleep time is ≥660 minutes (typically 12 to 14 hours) on 24-hour polysomnography or by wrist actigraphy in association with a sleep log

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 a week of wrist actigraphy)

No better explanation by another sleep disorder, medical or psychiatric disorder or use of drugs or medications

Diagnostic criteria have changed over the years and may change further as the MSLT may not produce consistent results in patients with idiopathic hypersomnia [30,31]. One study suggested that extending monitored sleep periods in the sleep laboratory beyond 24 hours may improve diagnostic accuracy [32]. Specifically, during 32 hours of controlled bed rest recording (after a standardized polysomnogram and modified MSLT), 19 hours of sleep over the 32-hour period appeared to be an optimal cut-off to identify idiopathic hypersomnia. At present, however, this protocol remains experimental and is not yet implemented in clinical settings.

DIFFERENTIAL DIAGNOSIS — Idiopathic hypersomnia is one of the less common causes of excessive daytime sleepiness (EDS), although it is not an uncommon diagnosis among patients referred to a sleep disorders clinic (table 3). More commonly encountered explanations, aside from chronically insufficient sleep and medication side effects, include narcolepsy type 1 or type 2, sleep-related breathing disorders, and psychiatric disorders.

Narcolepsy – Narcolepsy type 1 (narcolepsy with cataplexy) classically consists of the tetrad of EDS (sometimes with irresistible "sleep attacks"), cataplexy, hypnagogic hallucinations, and sleep paralysis. While cataplexy is highly specific for narcolepsy, its onset can be delayed for months or even years after the onset of EDS, and other patients never develop cataplexy (ie, narcolepsy type 2). This means that the diagnosis of idiopathic hypersomnia might be considered. In most cases, polysomnography and the multiple sleep latency test (MSLT) will confirm the diagnosis of narcolepsy based on an increased number of sleep-onset rapid eye movement periods (SOREMPs). (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Diagnostic criteria'.)

Certain aspects of the sleep history may also be helpful. In one series, patients with idiopathic hypersomnia were more likely to sleep nine or more hours per night, to have sleep drunkenness, and in particular, to take daytime naps that exceed 60 minutes, compared with patients with narcolepsy [3]. However, another published series did not show these differences [20].

Sleep-related breathing disorders – Sleep-related breathing disorders, such as obstructive sleep apnea, central sleep apnea, and sleep-related hypoventilation, must be differentiated from idiopathic hypersomnia. Subtle forms of obstructive sleep apnea in particular can sometimes be missed, leading to a premature diagnosis of idiopathic hypersomnia. Esophageal pressure monitoring may be useful in conjunction with standard polysomnography. (See "Polysomnography in the evaluation of sleep-disordered breathing in adults", section on 'Respiratory effort'.)

One older study showed that among 48 patients initially diagnosed with idiopathic hypersomnia, use of esophageal pressure monitoring to detect subtle sleep-disordered breathing led to reclassification of 15 (31 percent) of the subjects [25]. These subjects' subjective sleepiness, objectively-assessed sleepiness, and nocturnal sleep fragmentation responded to continuous positive airway pressure. In more recent years, use of nasal pressure monitoring and more sensitive definitions for hypopneas have probably made missed diagnoses of subtle OSA less common.

Hypersomnia associated with psychiatric disorders – Psychiatric disorders such as atypical depression, bipolar depression, and dysthymia are commonly associated with complaints of EDS. Other symptoms, such as depressed mood, long sleep times, and sleep inertia, can also overlap with those of idiopathic hypersomnia. Polysomnographic findings may be very similar, but the MSLT is more likely to show normal mean sleep latencies in patients with psychiatric disease. In unclear cases, formal psychiatric assessment or a trial of an antidepressant may be needed to distinguish the two.

TREATMENT — The underlying causes of idiopathic hypersomnia are not known, and therefore treatment is symptomatic. Nonpharmacologic approaches such as behavior modification are not generally effective. Unlike in narcolepsy, where scheduled naps can be beneficial, daytime naps in patients with idiopathic hypersomnolence are typically long and nonrestorative.

Pharmacotherapy — Pharmacologic approaches are derived from experience with medications to treat excessive daytime sleepiness (EDS) associated with narcolepsy (table 4); supporting data in idiopathic hypersomnia are limited to case reports, retrospective series, and small randomized trials [3,33-38]. Treatment options include modafinil, armodafinil, methylphenidate, amphetamines, and oxybates.

Among these, we suggest modafinil as first-line therapy, in part because it has a better side effect profile than other agents. Oxybates can be effective but have been considered a second-line therapy because of lack of US Food and Drug Administration (FDA) approval until 2021, high cost, and lack of insurer coverage as a treatment for idiopathic hypersomnia in most cases.

Modafinil – A typical starting dose of modafinil is 200 mg once each morning (to reduce the initial chance of headache), increasing if necessary within several days to 200 mg each morning and again at midday, or to 400 mg each morning. Armodafinil is started at 150 mg each morning and can be increased to 250 mg. (See "Treatment of narcolepsy in adults", section on 'Modafinil'.)

The effectiveness of modafinil has been demonstrated in two randomized trials in a total of 104 patients with idiopathic hypersomnia without long sleep time [36,39,40]. In both trials, patients treated with modafinil (200 mg daily given once in the morning or as two divided doses) had improved Epworth Sleepiness Scale (ESS) and clinical global impression rating scores compared with placebo. Mean sleep latency on the maintenance of wakefulness test (MWT) improved by approximately five minutes with treatment. Headache and gastrointestinal distress were the most common side effects attributed to modafinil. The utility of modafinil was also illustrated by a multicenter cross-sectional study of 104 patients with idiopathic hypersomnia and 126 patients with narcolepsy, all treated with modafinil [35]. In the subset of 63 idiopathic hypersomnia patients who completed the ESS before and after treatment, the mean improvement in the ESS score was 2.6 points, which was similar to that observed in narcolepsy patients. Forty-eight percent of patients reported at least one adverse effect, the most common being nervousness or irritability (14 percent), palpitations or tachycardia (13 percent), and headache (11 percent).

Oxybates – For patients who do not respond adequately to modafinil/armodafinil or traditional stimulants, we suggest a trial of oxybates (available in two forms, sodium oxybate and lower-sodium mixed oxybate salts). The active moiety of oxybates is gamma hydroxybutyrate (GHB), a metabolite of gamma amino butyric acid (GABA) that induces deep sedation. Oxybates can potently promote alertness and reduce cataplexy in patients with narcolepsy. Their mechanism of action in idiopathic hypersomnia is not established.

Mixed oxybate salts (Xywav) have received regulatory approval in the United States for both narcolepsy and idiopathic hypersomnia, whereas sodium oxybate (Xyrem) is approved only for narcolepsy. The active moiety and dosing are identical, and the only difference is that oxybate salts have 90 percent less sodium content. This can be an important advantage in some patients. Due to the potential for diversion as a "date rape" drug, access to oxybates is regulated in the United States, and prescribers and patients are required to register with the Risk Evaluation and Mitigation Strategies (REMS) program.

For oxybate salts, the manufacturer recommends individualized dosing in patients with idiopathic hypersomnia using either a once nightly regimen (starting at ≤3 g at bedtime and increasing by no more than 1.5 g per night per week) or twice nightly regimen (starting at ≤4.5 g per night divided into two doses, given 2.5 to 4 hours apart) [41]. We suggest waiting at least two to four weeks at a given dose level before increasing the dose, based on knowledge that in patients with narcolepsy, it can take several months or more for maximal effects to be seen. Experience in patients with narcolepsy suggests that twice-nightly dosing is often desirable. This is because patients wake up a few hours after taking oxybates, feeling fully alert, which can be a problem if it occurs in the middle of the intended sleep period. Side effects and safety precautions are discussed separately. (See "Treatment of narcolepsy in adults", section on 'Oxybates'.)

Oxybate salts were approved for idiopathic hypersomnia by the US Food and Drug Administration (FDA) based on results of a randomized discontinuation trial in 154 patients with idiopathic hypersomnia (19 to 75 years of age, median age 39 years) [42]. Oxybate salts were given either once or twice per night at the discretion of the treating clinician. Approximately 50 percent of patients were also taking another wake-promoting agent. During an open-label titration period in which both groups received oxybate salts, ESS scores improved by 9.6 points compared with the pretreatment baseline. After a two-week stable dose period, 115 patients entered a two-week randomized withdrawal period, during which subjects randomly assigned to placebo had worse ESS scores compared with those assigned to continue active treatment (median increase 7.5 versus 0.7 points). The rate of treatment discontinuation for side effects was 17 percent, most commonly for anxiety, insomnia, or nausea. Side effects were consistent with those seen in other studies of oxybates in patients with narcolepsy.

In an earlier retrospective study of sodium oxybate in 46 patients with idiopathic hypersomnia, 71 percent of patients reported improvement in morning sleep inertia, one of the more disabling and difficult symptoms of idiopathic hypersomnia [43]. Approximately half of patients stopped the drug due to side effects, most commonly nausea, dizziness, and headaches, a rate similar to that seen in patients with narcolepsy.

Others – The role of newer wake-promoting agents approved for use in patients with narcolepsy remains to be clarified. Some evidence suggests that pitolisant, a selective histamine H3 receptor antagonist/inverse agonist, may be helpful for a minority of patients with idiopathic hypersomnia [44]. (See "Treatment of narcolepsy in adults", section on 'Pitolisant'.)

Solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor with approval for both narcolepsy and residual sleepiness in obstructive sleep apnea, has not yet been studied in patients with idiopathic hypersomnia. (See "Treatment of narcolepsy in adults", section on 'Solriamfetol'.)

Under investigation – Additional therapies are under investigation.

Flumazenil – limited data suggest that compounded preparations of flumazenil, a GABA type A receptor antagonist, may benefit some patients with unexplained daytime sleepiness of central origin [11]. In a retrospective single-center series of 153 patients with refractory hypersomnolence due to idiopathic hypersomnia (24 percent), obstructive sleep apnea (23 percent), or other disorders, compounded sublingual or transdermal flumazenil was associated with sustained improvement in subjective sleepiness in 39 percent of patients [45]. The most commonly reported adverse effects were dizziness (13 percent), anxiety or other mood disturbance (13 percent), and headache (7 percent); one patient developed elevated liver function enzymes requiring discontinuation of drug. These preliminary data are encouraging and suggest that controlled studies of flumazenil are warranted.

Clarithromycin – Clarithromycin, a negative allosteric modulator of GABA type A receptors, may also improve subjective if not objective measures of sleepiness, as suggested in randomized, double-blind, crossover trial among 20 patients who completed the study [12].

Counseling and follow-up — Patients with idiopathic hypersomnia should be counseled to avoid activities that may be dangerous at home or at work. Patients should be warned about the danger of driving or operating dangerous machinery unless sleepiness is well controlled by medication [33]. (See "Drowsy driving: Risks, evaluation, and management".)

Patients should be followed at least annually and preferably every six months or more frequently to assess for adverse effects of medication, sleep or mood disturbances, cardiovascular or metabolic abnormalities, adequate control of excessive daytime sleepiness, adherence to medications, and any occupational or social issues [33].

PROGNOSIS — In most patients, symptoms of excessive daytime sleepiness (EDS) remain stable over time. A minority of patients (10 to 25 percent) will experience spontaneous improvement [3,4]. Most patients, two-thirds in one series of 77 patients [3] and three-quarters in another series of 42 patients [4], experience good, sustained improvement with medication. However, responses can be variable and often less than those observed in patients with narcolepsy.

SUMMARY AND RECOMMENDATIONS

Idiopathic hypersomnia is a sleep disorder that is characterized by chronic excessive daytime sleepiness, an irrepressible need to sleep or daytime lapses into sleep, and in some cases difficulty waking up from nocturnal sleep or daytime naps. The underlying pathophysiology is not well understood, and diagnosis requires exclusion of other more common causes of excessive sleepiness. (See "Approach to the patient with excessive daytime sleepiness".)

Idiopathic hypersomnia is a rare disorder, with a prevalence estimated at 20 to 50 per million. The mean age of symptom onset is 17 years and the mean age of diagnosis is 30 years. (See 'Epidemiology' above.)

The typical patient with idiopathic hypersomnia is an adolescent or young adult who complains of excessive daytime sleepiness (EDS), prolonged but unrefreshing naps, prolonged nocturnal sleep time, and great difficulty awakening from sleep. (See 'Clinical presentation' above.)

Idiopathic hypersomnia is largely a diagnosis of exclusion that is achieved by a thorough history, probing for symptoms suggestive of other common causes of EDS (table 3), and a nocturnal polysomnogram followed by a multiple sleep latency test. (See 'Diagnostic evaluation' above and 'Diagnostic criteria' above.)

The disorders most commonly considered in the differential diagnosis of idiopathic hypersomnia include narcolepsy, sleep-related breathing disorders, hypersomnia associated with psychiatric disorders, and chronically insufficient nocturnal sleep. (See 'Differential diagnosis' above.)

Treatment approaches are derived from experience with medications used to treat EDS associated with narcolepsy. Pharmacologic therapies that may have some benefit in patients with idiopathic hypersomnia include modafinil, armodafinil, methylphenidate, amphetamines, and oxybates. Of these, we suggest modafinil as first-line therapy (Grade 2C). (See 'Treatment' above.)

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  40. Trotti LM, Becker LA, Friederich Murray C, Hoque R. Medications for daytime sleepiness in individuals with idiopathic hypersomnia. Cochrane Database Syst Rev 2021; 5:CD012714.
  41. https://pp.jazzpharma.com/pi/xywav.en.USPI.pdf (Accessed on August 17, 2021).
  42. Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study. Lancet Neurol 2022; 21:53.
  43. Leu-Semenescu S, Louis P, Arnulf I. Benefits and risk of sodium oxybate in idiopathic hypersomnia versus narcolepsy type 1: a chart review. Sleep Med 2016; 17:38.
  44. Leu-Semenescu S, Nittur N, Golmard JL, Arnulf I. Effects of pitolisant, a histamine H3 inverse agonist, in drug-resistant idiopathic and symptomatic hypersomnia: a chart review. Sleep Med 2014; 15:681.
  45. Trotti LM, Saini P, Koola C, et al. Flumazenil for the Treatment of Refractory Hypersomnolence: Clinical Experience with 153 Patients. J Clin Sleep Med 2016; 12:1389.
Topic 14890 Version 18.0

References

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41 : Medications for daytime sleepiness in individuals with idiopathic hypersomnia.

42 : Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study.

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45 : Flumazenil for the Treatment of Refractory Hypersomnolence: Clinical Experience with 153 Patients.