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Idiopathic hypersomnia

Idiopathic hypersomnia
Literature review current through: Jan 2024.
This topic last updated: Nov 15, 2023.

INTRODUCTION — Idiopathic hypersomnia is a central disorder of hypersomnolence, characterized by at least three months of daily periods of irrepressible need to sleep, or daytime lapses into sleep or drowsiness [1]. Cataplexy consistent with narcolepsy type 1 is absent, and sleep laboratory testing does not suggest narcolepsy type 1 or 2. Objective evidence documents signs of excessive daytime sleepiness or at least 11 hours of total sleep time in a 24-hour period. Insufficient sleep is not present, and additional sleep and wake, circadian rhythm, or medical conditions or treatments are not better explanations for signs and symptoms.

The pathophysiology of idiopathic hypersomnia is not well understood. 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. In practice, no specific biomarker exists for idiopathic hypersomnia, which can sometimes remain not well distinguished from "mild" forms of sleep-disordered breathing, narcolepsy type 2, or insufficient sleep.

Based largely on sleep center referrals or large insurance claims databases, idiopathic hypersomnia appears to be significantly less common than narcolepsy, with a prevalence of approximately 20 to 100 cases per million people [3-7]. Some but not all reports have suggested females are affected more commonly than males.

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 [8]. Some cases may be precipitated by a viral illness [9], suggesting a possible autoimmune etiology. Reports of distinctive HLA markers have been inconsistent [10]. 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 [11].

One small study suggested that an as-yet undefined 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 [12]. 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 [13]. In contrast, a separate study could not confirm in vitro GABAA potentiation with cerebrospinal fluid from 15 patients with idiopathic hypersomnia [14]. 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 [15]. The latter correlated with subjective daytime sleepiness.

Orexin-A (also known as hypocretin-1), the wake-promoting neurotransmitter found to be absent or deficient in patients with narcolepsy type 1, is normal in idiopathic hypersomnia [16,17]. Standard cerebral spinal fluid tests are normal, although one study found altered dopamine and indoleacetic acid levels [18] and another suggested dysregulation of norepinephrine [19]. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Orexin/hypocretin'.)

Early studies suggested augmented slow wave activity on electroencephalography (EEG) of patients with idiopathic hypersomnia, with loss of the normal decline in slow wave activity during the nocturnal sleep period [20]. However, a meta-analysis found that patients with idiopathic hypersomnia showed less slow wave sleep and more rapid eye movement (REM) sleep relative to healthy controls [21]. This could imply that abnormal sleep contributes to the sleepiness in idiopathic hypersomnia.

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 and increased likelihood of long sleep times in these individuals.

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 (greater than 10). (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 (abrupt need to stop an activity and go to 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 and undisturbed. 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 [22]. 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 pronounced sleep inertia, with 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) [23]. 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 [24].

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 [25]. 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 generally is achieved by a thorough history, nocturnal polysomnography, and a multiple sleep latency test (MSLT) to ensure that other causes of EDS are not present.

Although a sleep log (table 1 and table 2) can be useful to clarify initial patient reports of long sleep durations, an activity monitor (actigraphy) or, if feasible, 24-hour polysomnographic monitoring 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 nocturnal sleep testing. Although a study of 33 patients with idiopathic hypersomnia found good correlation between total sleep time as measured by actigraphy and polysomnography [26], clinicians should be aware that the actigraphy software settings used to score wake and sleep can affect accuracy [27]. (See "Actigraphy in the evaluation of sleep disorders".)

The 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 (CSF) analysis, HLA testing, and quantification of CSF orexin-A (hypocretin-1) levels, are usually unnecessary 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. Of note, CSF orexin-A testing is not widely available in clinical laboratories in the United States and typically requires send-out arrangements. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Other laboratory tests'.)

Polysomnography — Patients should have a nocturnal polysomnogram to exclude other causes of EDS and especially subtle forms of obstructive sleep apnea (OSA) [28,29]. (See 'Differential diagnosis' below.)

In idiopathic hypersomnia, polysomnography may show a short sleep latency, increased total sleep time, increased sleep spindles, increased stability of stage N2 sleep once a bout of N2 is initiated, and variable changes in sleep efficiency and sleep stage distribution [3,4,21,24,30,31]. 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 none of these findings alone are specific enough to diagnose 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 [32]. 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 – often interpreted as at least six hours, in practice – 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 ≤8 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 [33,34].

DIAGNOSTIC CRITERIA — According to the International Classification of Sleep Disorders, third edition, Text Revision (ICSD-3-TR), a diagnosis of idiopathic hypersomnia requires all of the following [1]:

Daily periods of irrepressible need to sleep, or daytime lapses into drowsiness or sleep, that have occurred for at least three months

Cataplexy is not present

Polysomnography and multiple sleep latency test (MSLT) findings do not support a diagnosis of narcolepsy type 1 or 2 (see 'Multiple sleep latency test' above)

The presence of at least one of the following:

MSLT indicates a mean sleep latency of ≤8 minutes

Total 24-hour sleep time is ≥660 minutes (typically 12 to 14 hours) as measured by either 24-hour polysomnography that is performed after remediation of any chronic sleep deprivation or by wrist actigraphy in association with a sleep log, averaged over at least seven days with unrestricted sleep

Insufficient sleep syndrome is ruled out, if judged necessary, by failure of sleepiness to improve after an adequate trial of increased nocturnal time in bed, preferably documented on at least one week of actigraphy

No better explanation for signs and symptoms is provided by another sleep disorder, circadian rhythm sleep-wake disorder, medical disorder, mental disorder, or medication/substance use or withdrawal

Diagnostic criteria have changed over the years and may change further as the MSLT may not produce consistent results in patients with idiopathic hypersomnia [33,34]. One study suggested that extending monitored sleep periods in the sleep laboratory beyond 24 hours may improve diagnostic accuracy [35]. 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. More commonly encountered explanations, aside from chronically insufficient sleep and medication side effects, include sleep-related breathing disorders, narcolepsy type 1 or type 2, and psychiatric disorders (table 3). Distinguishing among these can be challenging [36].

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 [28]. 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.

Narcolepsy – Narcolepsy type 1 (narcolepsy with cataplexy) classically consists of the tetrad of EDS (sometimes with "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 (≥2) of sleep-onset rapid eye movement periods (SOREMPs). (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Diagnosis'.)

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 [23].

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 mainly from experience with medications to treat excessive daytime sleepiness (EDS) associated with narcolepsy (table 4). Supporting data in idiopathic hypersomnia consist largely of case reports and retrospective series, with few placebo-controlled randomized trials and no prospective comparative studies [3,37-42].

Treatment options reviewed in clinical practice guidelines from the American Academy of Sleep Medicine (AASM) include modafinil, clarithromycin, methylphenidate, pitolisant, and sodium oxybate; data on mixed-salt oxybates were not available for the 2021 guideline [41]. Absent comparative data, the choice of first-line therapy is based on side effect profiles, access, cost, and patient and clinician preferences.

For most patients, 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 are usually reserved for second-line therapy because the cost remains high, side effects are more frequent than with other wake-promoting medications, and insurance coverage as a treatment for idiopathic hypersomnia can be challenging.

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. Alternatively, 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 [40,43,44]. In both trials, patients treated with modafinil (200 mg daily given once in the morning or as two divided doses), compared with placebo, had improved Epworth Sleepiness Scale (ESS) and clinical global impression rating scores. 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 [39]. 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-salt oxybates). 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-salt oxybates (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) [45]. 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'.)

A once-nightly, extended-release form of sodium oxybate is approved by the US Food and Drug Administration (FDA) for adults with narcolepsy, but its effect in idiopathic hypersomnia remains to be demonstrated.

Mixed-salt oxybates were approved for idiopathic hypersomnia by the FDA based on results of a phase 3 randomized discontinuation trial in 154 patients with idiopathic hypersomnia (19 to 75 years of age, median age 39 years) [46]. Mixed-salt oxybates 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 mixed-salt oxybates, 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. Six-month open-label follow-up revealed sustained or improved efficacy over time and no new safety signals [47].

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 [48]. 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 [49], although insurance coverage may be difficult to obtain. (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 [12]. 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 [50]. 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 [13].

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 [37]. (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 [37].

PROGNOSIS — In most patients with idiopathic hypersomnia, symptoms of excessive daytime sleepiness (EDS) remain stable over time. A minority of patients (10 to 25 percent) will experience spontaneous improvement [3,4]. Many others experience good, sustained improvement with medication. However, responses can be variable and are often less satisfying than those observed in patients with narcolepsy.

More studies are needed to better understand the natural history. One complicating factor is that the diagnosis can be difficult to establish with certainty in some cases [36]. In one long-term follow-up study of 60 patients at a mean of 10 years after the initial diagnosis of idiopathic hypersomnia, 17 percent had experienced complete resolution of hypersomnolence, 3 percent had been recognized to have narcolepsy type 2, and 25 percent had developed other conditions that could explain their hypersomnolence [51]. Overall, only 55 percent retained a characteristic clinical diagnosis of idiopathic hypersomnia without doubts about the cause of sleepiness.

SUMMARY AND RECOMMENDATIONS

Epidemiology – Idiopathic hypersomnia is a rare disorder, with a prevalence estimated at 20 to 100 cases per million people. The mean age of symptom onset is 17 years, and the mean age of diagnosis is 30 years. (See 'Epidemiology' above.)

Pathogenesis – The pathogenesis of idiopathic hypersomnia is not well understood. A familial tendency is observed in up to half of patients, but no causative genes have been identified. (See 'Pathogenesis' above.)

Clinical presentation – Patients with idiopathic hypersomnia present with chronic excessive daytime sleepiness (EDS), prolonged but unrefreshing naps, prolonged nocturnal sleep time, and great difficulty awakening from sleep. (See 'Clinical presentation' above.)

Diagnosis – Idiopathic hypersomnia is a clinical diagnosis that should be considered in a teenager or young adult with chronic EDS with long unrefreshing daytime naps and difficulty arousing from sleep, in the absence of symptoms suggestive of other common causes of EDS (table 3). In the appropriate clinical context, the diagnosis is confirmed by nocturnal polysomnography followed by a multiple sleep latency test (MSLT). (See 'Diagnostic evaluation' above and 'Diagnostic criteria' above.)

Differential diagnosis – 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 – 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. Absent comparative data, the choice of first-line therapy is based on side effect profiles, access, cost, and patient and clinician preferences.

For most patients, we suggest modafinil as first-line therapy (Grade 2C). Traditional stimulants and oxybates (sodium oxybate or mixed-salt oxybates) are reasonable second-line therapies for those who do not respond adequately to modafinil. (See 'Treatment' above.)

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Topic 14890 Version 19.0

References

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