Idiopathic Hypersomnia¶
VERSION: 1.0 CREATED: February 7, 2026 STATUS: Approved
DIAGNOSIS: Idiopathic Hypersomnia
ICD-10: G47.11 (Idiopathic hypersomnia with long sleep time), G47.12 (Idiopathic hypersomnia without long sleep time)
CPT CODES: 95810 (Polysomnography (PSG)), 95805 (Multiple Sleep Latency Test (MSLT)), 95803 (Actigraphy (2 weeks)), 85025 (CBC), 80053 (CMP), 84443 (TSH), 82607 (Vitamin B12), 82728 (Serum ferritin), 80307 (Urine drug screen), 70553 (MRI brain with and without contrast), 81383 (HLA-DQB1*06:02 typing)
SYNONYMS: Idiopathic hypersomnia, IH, primary hypersomnia, idiopathic hypersomnolence, excessive daytime sleepiness NOS, central disorder of hypersomnolence, non-narcoleptic hypersomnia, long sleeper syndrome
SCOPE: Diagnosis and management of idiopathic hypersomnia in adults. Covers the diagnostic workup distinguishing IH from narcolepsy type 2, insufficient sleep syndrome, and other causes of excessive daytime sleepiness. Includes PSG/MSLT interpretation, pharmacologic treatment of EDS and sleep inertia/sleep drunkenness, and long-term management. Excludes narcolepsy (separate plan), hypersomnia due to medical conditions, Kleine-Levin syndrome, and medication-induced hypersomnia.
DEFINITIONS: - Idiopathic Hypersomnia (IH): Central disorder of hypersomnolence characterized by excessive daytime sleepiness and/or prolonged total sleep time (≥11 hours/24 hours) without cataplexy and without ≥2 SOREMPs on MSLT; etiology unknown - Sleep Drunkenness (Severe Sleep Inertia): Profound difficulty awakening from sleep with prolonged confusion, disorientation, automatic behavior, and impaired cognitive function lasting 30 minutes to several hours after awakening; hallmark feature of IH - Excessive Daytime Sleepiness (EDS): Inability to maintain sustained wakefulness during the day despite adequate or prolonged nocturnal sleep; distinguishable from fatigue by the irrepressible need to sleep - Sleep-Onset REM Period (SOREMP): REM sleep occurring within 15 minutes of sleep onset on PSG or MSLT; fewer than 2 SOREMPs on MSLT is required for IH diagnosis (≥2 SOREMPs suggests narcolepsy) - Long Sleep Time Phenotype: Total 24-hour sleep time ≥660 minutes (11 hours) documented by PSG or actigraphy; present in a subset of IH patients - Mean Sleep Latency: Average time to fall asleep across nap opportunities on MSLT; ≤8 minutes indicates pathological sleepiness
DIAGNOSTIC CRITERIA (ICSD-3-TR):
Idiopathic Hypersomnia — All of the following:
- Daily periods of irrepressible need to sleep or daytime lapses into sleep for ≥3 months
- Cataplexy is absent
- MSLT shows fewer than 2 SOREMPs (or MSLT is not performed)
- At least one of the following:
- MSLT mean sleep latency ≤8 minutes, OR
- Total 24-hour sleep time ≥660 minutes (11 hours) on 24-hour PSG or wrist actigraphy (averaged over ≥7 days, adjusted for age)
- Insufficient sleep syndrome is ruled out (actigraphy or sleep diary for ≥2 weeks demonstrating habitual sleep duration ≥7 hours/night)
- Not better explained by another sleep disorder, medical condition, psychiatric disorder, medication, or substance use
Key Clinical Features:
- Excessive daytime sleepiness (100% of patients; present despite adequate or prolonged nocturnal sleep)
- Sleep drunkenness / severe sleep inertia (~50-80%; hallmark feature distinguishing IH from narcolepsy)
- Prolonged, unrefreshing naps (naps in IH are long and non-restorative, unlike the short refreshing naps in narcolepsy)
- Difficulty awakening from sleep despite alarms (often requiring assistance from others)
- Cognitive fog / "brain fog" during the day (impaired concentration, attention, and memory)
- Prolonged nocturnal sleep (≥11 hours in the long sleep time phenotype)
Epworth Sleepiness Scale (ESS) Severity: - Normal: 0-10 - Mild sleepiness: 11-14 - Moderate sleepiness: 15-17 - Severe sleepiness: 18-24
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
1. LABORATORY WORKUP¶
1A. Essential/Core Labs (All Patients)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CBC (CPT 85025) | Exclude anemia contributing to fatigue and hypersomnia | Normal | ROUTINE | ROUTINE | ROUTINE | - |
| CMP (CPT 80053) | Renal/hepatic function; electrolytes; pre-treatment baseline | Normal | ROUTINE | ROUTINE | ROUTINE | - |
| TSH (CPT 84443) | Exclude hypothyroidism as cause of fatigue/hypersomnia | Normal | ROUTINE | ROUTINE | ROUTINE | - |
| Vitamin B12 (CPT 82607) | B12 deficiency can cause fatigue and cognitive impairment mimicking IH | >400 pg/mL | - | ROUTINE | ROUTINE | - |
| Serum ferritin (CPT 82728) | Iron deficiency contributes to EDS and restless legs; confounds sleep quality | >30 ng/mL | - | ROUTINE | ROUTINE | - |
| Urine drug screen (CPT 80307) | Exclude substance use causing hypersomnia; mandatory before MSLT | Negative | URGENT | ROUTINE | ROUTINE | - |
1B. Extended Workup (Second-line)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Serum iron / TIBC | Comprehensive iron assessment if ferritin borderline; iron deficiency contributes to fatigue | Normal iron panel | - | ROUTINE | ROUTINE | - |
| Morning cortisol (8 AM draw) | Exclude adrenal insufficiency as cause of fatigue and hypersomnia | >10 mcg/dL | - | - | EXT | - |
| HbA1c (CPT 83036) | Diabetes screening; metabolic contributors to fatigue and sleepiness | <5.7% | - | ROUTINE | ROUTINE | - |
| Hepatic function panel (CPT 80076) | Baseline before medication initiation; exclude hepatic encephalopathy | Normal | - | ROUTINE | ROUTINE | - |
| Prolactin | Evaluate for hypothalamic/pituitary dysfunction if structural lesion suspected | Normal (2-18 ng/mL female, 2-18 ng/mL male) | - | - | EXT | - |
1C. Rare/Specialized¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CSF hypocretin-1 / orexin-A (sent to Stanford reference lab) | Definitively exclude narcolepsy type 1; must be >110 pg/mL to support IH diagnosis | >110 pg/mL (excludes NT1); ≤110 pg/mL reclassifies as NT1 | - | EXT | EXT | - |
| HLA-DQB1*06:02 typing (CPT 81383) | Supportive for narcolepsy if positive (>90% of NT1); absence helps support IH diagnosis but not definitive | Negative favors IH over NT1 (but present in 25% of general population) | - | - | EXT | - |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Polysomnography (PSG) (CPT 95810) | Night before MSLT; required for MSLT interpretation | Exclude OSA, PLMD, other primary sleep disorders; document total sleep time; note any SOREMP within 15 min | None | - | ROUTINE | ROUTINE | - |
| Multiple Sleep Latency Test (MSLT) (CPT 95805) | Day following PSG; at least 2 weeks off REM-suppressant medications | Mean sleep latency ≤8 min with <2 SOREMPs (≥2 SOREMPs reclassifies as narcolepsy) | Must have preceding PSG; stop REM-suppressants 2 weeks prior | - | ROUTINE | ROUTINE | - |
| Actigraphy (≥2 weeks) (CPT 95803) | Pre-MSLT; essential to exclude insufficient sleep syndrome | Document habitual sleep duration ≥7 hours/night; may also demonstrate total sleep ≥11 hours supporting IH with long sleep time | None | - | - | ROUTINE | - |
| Epworth Sleepiness Scale (ESS) | Initial evaluation and each follow-up visit | Quantify sleepiness severity; scores >10 abnormal | None | ROUTINE | ROUTINE | ROUTINE | - |
| Sleep diary (≥2 weeks) | Pre-MSLT; complements actigraphy | Confirm adequate habitual sleep (≥7 hours/night); document sleep/wake patterns, nap timing, sleep inertia severity | None | - | - | ROUTINE | - |
2B. Extended¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain without contrast (CPT 70553) | If structural lesion suspected (hypothalamic, brainstem) or atypical features | Rule out hypothalamic mass, demyelination, brainstem lesion, hydrocephalus | Per MRI contraindications | - | ROUTINE | ROUTINE | - |
| Extended PSG (24-hour monitoring) | If total sleep time criteria needed for diagnosis and actigraphy is equivocal | Document total 24-hour sleep time ≥660 minutes (11 hours); confirms long sleep time phenotype | None; requires dedicated sleep lab with 24-hour monitoring capability | - | EXT | EXT | - |
2C. Rare/Specialized¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Maintenance of Wakefulness Test (MWT) (CPT 95805) | Treatment response monitoring; fitness-for-duty and driving safety evaluation | Mean latency >8 min suggests adequate wakefulness (normal >40 min) | None | - | - | EXT | - |
| Pupillometry | If objective sleepiness quantification needed independent of MSLT | Increased pupillary unrest correlates with sleepiness | None | - | - | EXT | - |
| Quantitative EEG | Research setting; alpha power and spectral analysis during wakefulness | Increased theta activity in wakefulness may correlate with hypersomnolence | None | - | - | EXT | - |
3. TREATMENT¶
3A. Non-Pharmacologic Treatment (All Patients)¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Strategic alarm systems | - | Sleep inertia/sleep drunkenness; difficulty awakening | N/A :: - :: daily :: Multiple staged alarms at 5-10 minute intervals with escalating volume; place alarms away from bed; consider vibrating alarms, light-based alarms (dawn simulators), and bed-shaking devices; recruit household member for backup awakening | None | Adherence; awakening success | - | ROUTINE | ROUTINE | - |
| Light therapy upon awakening | - | Sleep inertia; circadian rhythm support; enhance morning alertness | N/A :: - :: daily :: 10,000 lux broad-spectrum light box for 30 minutes immediately upon awakening; may combine with dawn simulator alarm; morning light exposure helps consolidate the circadian wake signal | Retinal conditions; bipolar disorder (may trigger mania); photosensitizing medications | Mood; eye discomfort; headache | - | - | ROUTINE | - |
| Sleep hygiene optimization | - | Consolidate nocturnal sleep; maximize sleep quality | N/A :: - :: daily :: Regular sleep-wake schedule (same wake time daily is critical); 7-9 hours nightly; cool dark room; limit screen time before bed; avoid alcohol/sedatives | None | Adherence; symptom response | - | ROUTINE | ROUTINE | - |
| Safety counseling | - | Prevent injury from sleepiness and impaired awakening | N/A :: - :: once :: Driving restrictions until EDS controlled; avoid heights, swimming alone, operating heavy machinery; inform employer; discuss safety risks of sleep drunkenness (e.g., responding to alarms during confusion) | None | Compliance; driving status | ROUTINE | ROUTINE | ROUTINE | - |
| Avoid sedating substances | - | Prevent worsening of EDS and sleep inertia | N/A :: - :: N/A :: Avoid alcohol, sedating antihistamines, benzodiazepines; limit caffeine timing (morning only; avoid late-day use that disrupts nocturnal sleep) | None | Symptom response | ROUTINE | ROUTINE | ROUTINE | - |
3B. First-Line Pharmacologic Treatment - Wake-Promoting Agents¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Modafinil (Provigil) | PO | First-line wake-promoting agent for EDS in IH | 100 mg :: PO :: daily :: Start 100 mg each morning; increase to 200 mg daily after 1 week; may split 200 mg AM + 200 mg early afternoon if needed; max 400 mg/day; first-line for EDS in IH | Hypersensitivity; severe hepatic impairment; may reduce efficacy of hormonal contraceptives | Blood pressure; rash (rare Stevens-Johnson syndrome); sleep quality; contraceptive efficacy counseling | - | ROUTINE | ROUTINE | - |
| Armodafinil (Nuvigil) | PO | First-line wake-promoting agent for EDS; longer half-life provides sustained daytime coverage | 150 mg :: PO :: daily :: Start 150 mg each morning; may increase to 250 mg daily; longer half-life than modafinil provides more sustained wakefulness; max 250 mg/day | Hypersensitivity; severe hepatic impairment; may reduce efficacy of hormonal contraceptives | Blood pressure; rash (rare Stevens-Johnson syndrome); sleep quality; contraceptive efficacy counseling | - | ROUTINE | ROUTINE | - |
| Low-sodium oxybate (Xywav) | PO | FDA-approved for IH; only medication demonstrated to reduce total sleep time and improve sleep inertia; REMS program required | 4.5 g/night :: PO :: BID nightly :: Start 4.5 g/night divided into 2 equal doses (2.25 g at bedtime + 2.25 g 2.5-4 hours later); titrate by 1.5 g/night every 1-2 weeks; effective range 6-9 g/night; max 9 g/night; FDA-approved for IH (only drug with this indication) | Succinic semialdehyde dehydrogenase deficiency; concurrent sedative-hypnotics or alcohol; concurrent opioids; untreated sleep-disordered breathing | Respiratory depression; CNS depression; sleepwalking; depression/suicidality screening; sodium levels; REMS compliance monitoring; abuse potential | - | ROUTINE | ROUTINE | - |
3C. Second-Line Pharmacologic Treatment¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Solriamfetol (Sunosi) | PO | EDS in IH refractory to modafinil/armodafinil; dual dopamine/norepinephrine reuptake inhibitor | 75 mg :: PO :: daily :: Start 75 mg once daily upon awakening; may increase to 150 mg daily after ≥3 days; max 150 mg/day; monitor blood pressure as dose-dependent hypertension may occur | Concurrent MAOIs; uncontrolled hypertension; severe renal impairment (eGFR <15); end-stage renal disease | Blood pressure; heart rate; psychiatric symptoms; weight; renal function | - | ROUTINE | ROUTINE | - |
| Methylphenidate (Ritalin) | PO | EDS refractory to first-line agents; rapid onset of action | 5 mg :: PO :: BID :: Start 5 mg BID (morning and early afternoon); titrate by 5-10 mg/week; max 60 mg/day; avoid evening dosing; Schedule II controlled substance | Concurrent MAOIs; severe anxiety or agitation; motor tics/Tourette syndrome; glaucoma; structural cardiac abnormalities | Blood pressure; heart rate; weight; appetite; psychiatric symptoms; abuse potential (Schedule II) | - | ROUTINE | ROUTINE | - |
| Dextroamphetamine (Dexedrine) | PO | EDS refractory to first-line agents; potent wake-promoting agent | 5 mg :: PO :: BID :: Start 5 mg BID (morning and early afternoon); titrate by 5 mg/week; max 60 mg/day; avoid evening dosing; Schedule II controlled substance | Concurrent MAOIs; advanced atherosclerosis; symptomatic cardiovascular disease; moderate-severe hypertension; glaucoma; agitated states; history of drug abuse | Blood pressure; heart rate; weight; appetite; psychiatric symptoms; abuse potential (Schedule II) | - | ROUTINE | ROUTINE | - |
| Pitolisant (Wakix) | PO | EDS in IH; histamine H3 receptor inverse agonist; non-controlled substance | 8.9 mg :: PO :: daily :: Start 8.9 mg once daily upon awakening; titrate weekly: 8.9 mg to 17.8 mg to 35.6 mg; max 35.6 mg/day; non-controlled substance (advantage over stimulants) | Severe hepatic impairment; concurrent strong CYP2D6 inhibitors (max 17.8 mg); QT-prolonging drugs | QTc interval if risk factors; hepatic function; insomnia; headache; nausea | - | ROUTINE | ROUTINE | - |
3D. Sleep Inertia / Sleep Drunkenness Management¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Caffeine (adjunctive) | PO | Sleep inertia upon awakening; adjunctive to primary wake-promoting therapy | 100 mg :: PO :: daily :: 100-200 mg upon awakening (equivalent to 1-2 cups coffee); use as bridge while waiting for primary medication effect; avoid after noon to protect nocturnal sleep quality | Cardiac arrhythmias; severe anxiety disorder; gastric ulcer | Anxiety; palpitations; sleep quality; tolerance development | - | ROUTINE | ROUTINE | - |
| Flumazenil | SL | Severe sleep inertia/sleep drunkenness refractory to standard treatments; investigational GABA-A receptor antagonist for IH | 0.5 mg :: SL :: daily :: Start 0.5 mg sublingual once daily upon awakening; may increase to 1 mg SL daily; off-label use; limited evidence but promising results in IH; addresses putative GABA-A receptor potentiation in IH pathophysiology | Benzodiazepine dependence (may precipitate withdrawal); epilepsy controlled with benzodiazepines; hypersensitivity | Seizure risk; anxiety; headache; nausea; duration of effect (short half-life may limit efficacy) | - | - | EXT | - |
3E. Adjunctive / Symptomatic Treatment¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Melatonin | PO | Circadian rhythm support; consolidate nocturnal sleep if fragmented | 3 mg :: PO :: QHS :: 3-5 mg 30 minutes before target bedtime; may help regulate sleep-wake timing; useful if circadian drift present | Autoimmune conditions (theoretical) | Daytime sedation; next-day grogginess; interaction with sleep inertia | - | ROUTINE | ROUTINE | - |
| Clarithromycin | PO | Investigational for IH; negative allosteric modulator of GABA-A receptors; off-label | 500 mg :: PO :: BID :: 500 mg twice daily; rationale similar to flumazenil (targets GABA-A system); off-label; limited evidence from small studies; potential alternative when flumazenil unavailable | Macrolide hypersensitivity; concurrent colchicine, pimozide, or cisapride; QT prolongation risk; hepatic impairment | QTc interval; hepatic function; GI side effects; drug interactions (potent CYP3A4 inhibitor); antibiotic stewardship considerations | - | - | EXT | - |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Sleep medicine specialist for PSG/MSLT scheduling, diagnosis confirmation, treatment initiation and optimization (IH requires specialist-level interpretation of MSLT results) | - | ROUTINE | ROUTINE | - |
| Neuropsychology if cognitive complaints are prominent (IH-related cognitive fog requires formal testing to document deficits and guide accommodations) | - | - | ROUTINE | - |
| Occupational medicine for fitness-for-duty evaluation, driving safety assessment, and workplace accommodation (IH poses significant occupational safety risk particularly due to sleep inertia) | - | - | ROUTINE | - |
| Psychiatry if comorbid depression or anxiety requiring treatment (common comorbidities in IH; must distinguish depression-related hypersomnia from IH) | - | ROUTINE | ROUTINE | - |
| Social work for disability evaluation and community resource coordination (IH causes significant functional impairment; many patients qualify for workplace accommodations under ADA) | - | - | ROUTINE | - |
4B. Patient/Family Instructions¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Idiopathic hypersomnia is a chronic neurological condition of the brain's sleep-wake regulation system; it is not laziness, depression, or a behavioral choice | ROUTINE | ROUTINE | ROUTINE | - |
| Do not drive until excessive daytime sleepiness is adequately controlled with treatment (risk of drowsy driving is highest in the morning due to sleep inertia) | ROUTINE | ROUTINE | ROUTINE | - |
| Use multiple alarm systems with escalating intensity to overcome sleep drunkenness; place alarms away from bed; consider recruiting a household member as backup for important mornings | - | ROUTINE | ROUTINE | - |
| Naps in IH are typically long and unrefreshing (unlike narcolepsy where short naps are restorative); limit nap duration to 30-60 minutes to avoid worsening sleep inertia from deep nap sleep | - | ROUTINE | ROUTINE | - |
| Notify all providers about IH diagnosis before any sedation or anesthesia (patients with IH may have prolonged recovery from sedation due to baseline hypersomnolence) | ROUTINE | ROUTINE | ROUTINE | - |
| Avoid alcohol and sedating medications (antihistamines, benzodiazepines, muscle relaxants) which worsen excessive sleepiness and sleep drunkenness | ROUTINE | ROUTINE | ROUTINE | - |
| If prescribed Xywav (low-sodium oxybate): REMS enrollment required; prepare both doses before bedtime; do not take within 2 hours of food; no alcohol; store securely | - | ROUTINE | ROUTINE | - |
| Hypersomnia Foundation (hypersomniafoundation.org) for patient resources, support groups, and research updates specific to IH | - | - | ROUTINE | - |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Maintain consistent sleep-wake schedule with a strict fixed wake time every day (including weekends) to consolidate the circadian wake signal | - | ROUTINE | ROUTINE | - |
| Morning light exposure (30 minutes of bright light or outdoor light immediately upon awakening) to counteract sleep inertia and reinforce the circadian wake signal | - | - | ROUTINE | - |
| Regular moderate exercise (30 minutes daily, morning preferred) to improve daytime alertness; avoid vigorous exercise close to bedtime which may fragment sleep | - | - | ROUTINE | - |
| Avoid heavy meals during the day as postprandial sleepiness compounds existing EDS in IH patients | - | ROUTINE | ROUTINE | - |
| Strategic napping: unlike narcolepsy, naps in IH are generally unrefreshing; if naps are used, limit to 20-30 minutes and set multiple alarms (longer naps worsen sleep inertia) | - | ROUTINE | ROUTINE | - |
| Inform employer about IH diagnosis for reasonable workplace accommodations under ADA (flexible start time to accommodate sleep inertia, scheduled break periods, avoidance of monotonous or safety-critical tasks during low-alertness periods) | - | - | ROUTINE | - |
| Avoid alcohol and sedatives which exacerbate EDS; limit caffeine to morning hours to avoid disrupting nocturnal sleep quality | - | ROUTINE | ROUTINE | - |
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Narcolepsy type 2 | MSLT shows ≥2 SOREMPs; naps are short and refreshing; less prominent sleep inertia; cataplexy absent (same as IH); MSLT is the primary differentiator | MSLT: ≥2 SOREMPs (NT2) vs. <2 SOREMPs (IH) |
| Insufficient sleep syndrome | Most common mimic; chronic volitional sleep restriction; resolves with sleep extension to ≥7-8 hours/night; normal MSLT after adequate sleep | Actigraphy ≥2 weeks showing habitual sleep <7 hours; resolution of EDS with sleep extension trial |
| Long sleeper (normal variant) | Constitutionally long sleep need (≥10 hours) but feel refreshed upon awakening; no EDS when sleep need is met; no sleep drunkenness | Sleep extension trial: EDS resolves when full sleep need met; ESS normal when well-rested |
| Medication-induced hypersomnia | Temporal relationship to medication initiation (sedating antidepressants, antipsychotics, antihistamines, anticonvulsants, opioids); resolves with dose reduction or discontinuation | Medication review; temporal correlation; MSLT normalizes after medication discontinuation |
| Depression-related hypersomnia | Depressed mood, anhedonia, psychomotor retardation; fatigue more than true sleepiness; may have increased time in bed but MSLT usually normal; sleep often fragmented | Psychiatric evaluation; PHQ-9 ≥10; MSLT typically mean latency >8 min and <2 SOREMPs |
| Obstructive sleep apnea (OSA) | Snoring, witnessed apneas, obesity; EDS improves with CPAP; no sleep drunkenness; fragmented sleep on PSG | PSG with respiratory scoring; AHI >5 events/hour; EDS resolves with CPAP treatment |
| Hypothyroidism | Fatigue, cold intolerance, weight gain, constipation, dry skin; generalized slowing; no SOREMPs | TSH elevated; free T4 low; EDS resolves with thyroid replacement |
| Kleine-Levin syndrome | Recurrent episodes of profound hypersomnia lasting days-weeks with cognitive and behavioral disturbances (hyperphagia, hypersexuality, derealization); completely asymptomatic between episodes | Episodic pattern (recurrence-remission); normal inter-episode PSG/MSLT; onset typically in adolescence |
| Post-traumatic hypersomnia | EDS developing after TBI; temporal relationship to head injury; may have prolonged sleep time similar to IH; may or may not resolve over time | History of TBI preceding hypersomnia; neuroimaging may show injury; onset within 6-12 months of TBI |
| Circadian rhythm sleep-wake disorder | Misalignment of endogenous circadian rhythm (delayed sleep-wake phase disorder most common); sleepiness is time-of-day dependent | Actigraphy showing delayed sleep-wake phase; sleep log; DLMO (dim light melatonin onset) |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Epworth Sleepiness Scale (ESS) | Each visit (every 3 months during titration; every 6 months when stable) | ESS ≤10 (normal range) | Adjust wake-promoting agent dose; add second agent; switch therapy; consider Xywav | - | ROUTINE | ROUTINE | - |
| Idiopathic Hypersomnia Severity Scale (IHSS) | Each visit if available | Improvement from baseline (no universal threshold established) | Correlate with ESS and functional status; adjust treatment accordingly | - | - | ROUTINE | - |
| Sleep inertia severity (patient-reported) | Each visit | Reduction in duration and severity of sleep drunkenness; ability to awaken independently | Optimize Xywav dosing (most effective for sleep inertia); adjust alarm strategy; consider flumazenil | - | ROUTINE | ROUTINE | - |
| Blood pressure | Each visit; more frequently if on stimulants or solriamfetol | <140/90 mmHg | Dose reduction; add antihypertensive; switch to non-stimulant agent | ROUTINE | ROUTINE | ROUTINE | - |
| Heart rate | Each visit if on stimulants | <100 bpm resting | Dose reduction; cardiology referral if persistent tachycardia | ROUTINE | ROUTINE | ROUTINE | - |
| Weight/BMI | Every 3-6 months | Stable or improving | Dietary counseling; exercise; evaluate medication effects (stimulants may cause weight loss, inactivity from hypersomnia may cause weight gain) | - | ROUTINE | ROUTINE | - |
| Mood/depression screening (PHQ-9) | Every 3-6 months | PHQ-9 <5 | Psychiatric referral; adjust medications; monitor suicidality; distinguish IH-related cognitive fog from depression | - | ROUTINE | ROUTINE | - |
| Sodium levels (if on Xywav) | Baseline; 1 month after initiation; then every 6 months | Normal serum sodium (136-145 mEq/L) | Dietary sodium counseling; dose adjustment; endocrine evaluation if persistently abnormal | - | ROUTINE | ROUTINE | - |
| REMS compliance (if on Xywav) | Each visit | Current enrollment; pharmacy verification | Re-enroll if lapsed; review adherence barriers; verify prescriber/pharmacy enrollment | - | ROUTINE | ROUTINE | - |
| Driving safety assessment | Every 6-12 months; sooner if symptoms worsen | Adequate wakefulness for safe driving; ability to awaken from sleep inertia within reasonable time | Reinforce driving restrictions; consider MWT for formal assessment; adjust treatment | - | - | ROUTINE | - |
| Substance use screening (if on stimulants) | Every 6-12 months | No misuse | Consider non-stimulant alternatives (pitolisant, Xywav); refer to addiction medicine if indicated | - | - | ROUTINE | - |
| CMP / hepatic function | Annually; more frequently if on pitolisant or clarithromycin | Normal ALT/AST | Dose reduction or discontinuation of hepatotoxic medication | - | ROUTINE | ROUTINE | - |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| Outpatient management | Majority of patients; newly suspected or established IH for diagnostic workup and chronic management; almost all IH management is outpatient |
| Admit for PSG/MSLT | Patients requiring in-lab polysomnography followed by next-day MSLT; ensure REM-suppressants discontinued ≥2 weeks prior |
| Admit for 24-hour PSG | Rare; if extended monitoring needed to document total 24-hour sleep time ≥660 minutes when actigraphy is equivocal or technically inadequate |
| Admit to floor | Rarely indicated; severe sleep drunkenness causing immediate safety concern (e.g., patient living alone unable to awaken for emergencies); concurrent medical condition requiring inpatient management |
| ICU admission | Not applicable for IH |
| Sleep medicine referral | All patients with suspected IH for PSG/MSLT interpretation, diagnosis confirmation, and treatment initiation |
| Neurology referral | Atypical presentation; suspected secondary cause of hypersomnia; treatment-refractory cases |
| Follow-up frequency | Every 2-4 weeks during initial medication titration; every 3 months during first year; every 6 months once stable |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| ICSD-3-TR diagnostic criteria for idiopathic hypersomnia (daily EDS ≥3 months, <2 SOREMPs, mean latency ≤8 min or total sleep ≥660 min, insufficient sleep excluded) | Consensus guidelines | AASM. International Classification of Sleep Disorders, 3rd ed., Text Revision (ICSD-3-TR) 2023 |
| Comprehensive review of IH pathophysiology, diagnosis, and management; evidence for GABA-A receptor potentiation hypothesis | Expert review | Dauvilliers et al. Brain 2017 |
| Flumazenil as treatment for IH targeting GABA-A receptor abnormality; demonstrated improvement in subjective sleepiness and sleep inertia | Class III, pilot data | Trotti et al. Sleep 2016 |
| Diagnosis of central disorders of hypersomnolence; distinction between IH and narcolepsy type 2; MSLT limitations and biomarker development | Expert review/guideline | Lammers et al. Lancet Neurol 2020 |
| Low-sodium oxybate (Xywav) efficacy for IH; reduced EDS, sleep inertia, and total sleep time; basis for FDA approval in IH | Class I, Level A (RCT) | Thorpy et al. Sleep 2019 |
| IH treatment update; review of modafinil, stimulants, oxybate, pitolisant, and investigational agents for IH management | Expert review | Ali et al. J Clin Sleep Med 2023 |
| Modafinil efficacy for EDS; first-line wake-promoting agent (evidence primarily from narcolepsy trials, extrapolated to IH) | Class I, Level A (extrapolated) | US Modafinil in Narcolepsy Multicenter Study Group. Neurology 2000 |
| Solriamfetol efficacy for EDS; dopamine/norepinephrine reuptake inhibitor (FDA approved for narcolepsy and OSA; off-label for IH) | Class I, Level A (extrapolated) | Thorpy et al. Ann Neurol 2019 |
| Pitolisant efficacy for EDS; histamine H3 inverse agonist; non-controlled substance option (off-label for IH) | Class I, Level A (extrapolated) | Dauvilliers et al. Lancet Neurol 2013 |
| European guideline on management of central hypersomnolence; treatment recommendations applicable to IH (modafinil/armodafinil first-line for EDS) | Guideline, GRADE methodology | Bassetti et al. J Sleep Res 2021 |
| Xywav REMS program required for prescribing; FDA mandate for safety monitoring | FDA mandate | FDA labeling / REMS |
| MSLT interpretation and validation; <2 SOREMPs with mean latency ≤8 min distinguishes IH from NT2 | Class II | Arand et al. Sleep 2005 |
NOTES¶
- Idiopathic hypersomnia is a central disorder of hypersomnolence with unknown etiology; the "idiopathic" designation means no identifiable cause despite thorough evaluation
- Sleep drunkenness (severe sleep inertia) is the most characteristic feature of IH and a major source of functional impairment; patients may exhibit confusion, automatic behavior, and even aggression upon forced awakening
- Unlike narcolepsy, naps in IH are typically prolonged (30-60+ minutes) and non-refreshing; this is a key clinical distinction during history taking
- The ICSD-3-TR eliminated the prior division into IH with and without long sleep time as separate diagnoses; both are now classified under a single IH diagnosis with total sleep time ≥660 minutes as one of two objective criteria (the other being MSLT mean latency ≤8 minutes)
- MSLT has test-retest variability (~20% of patients may shift between IH and NT2 on repeat testing); clinical context is essential for diagnosis
- Insufficient sleep syndrome is the most common mimic and must be rigorously excluded with ≥2 weeks of actigraphy or sleep diary showing adequate habitual sleep before MSLT is performed
- Low-sodium oxybate (Xywav) is currently the only FDA-approved medication specifically for IH; it is the only treatment shown to reduce both EDS and total sleep time
- The GABA-A receptor potentiation hypothesis proposes that a substance in IH patients' CSF enhances GABA-A receptor function, producing a state similar to chronic low-grade sedation; this is the rationale for flumazenil and clarithromycin as investigational treatments
- Modafinil, armodafinil, stimulants, pitolisant, and solriamfetol are used off-label for IH based on extrapolation from narcolepsy trials and clinical experience
- Comorbid depression is common in IH (30-50%); it may be a consequence of chronic hypersomnia rather than a cause, and requires concurrent treatment
- IH onset is typically in late adolescence or young adulthood; diagnosis is often delayed years due to overlap with depression, insufficient sleep, and low disease awareness
- Pregnancy management: discontinue Xywav and stimulants; non-pharmacologic measures (alarms, light therapy, scheduled rest) become primary treatment; modafinil is pregnancy category C with limited data
- Spontaneous remission occurs in a minority of patients (~14-25%); periodic reassessment of ongoing need for treatment is warranted
CHANGE LOG¶
v1.0 (February 7, 2026) - Initial template creation - ICSD-3-TR diagnostic criteria for idiopathic hypersomnia - Comprehensive pharmacologic treatment: wake-promoting agents (modafinil, armodafinil, low-sodium oxybate), second-line agents (solriamfetol, methylphenidate, dextroamphetamine, pitolisant), sleep inertia management (caffeine, flumazenil), adjunctive agents (melatonin, clarithromycin) - Non-pharmacologic interventions including strategic alarm systems, light therapy, and safety counseling - Structured dosing format with :: delimiters for all medications - 10-column treatment tables throughout - PubMed citations for all major evidence sources - Differential diagnosis distinguishing IH from narcolepsy type 2, insufficient sleep syndrome, long sleeper, and other hypersomnias
APPENDIX A: MSLT Preparation Protocol for IH Diagnosis¶
Prerequisites for Valid MSLT (Same as Narcolepsy MSLT Protocol):
- Sleep diary or actigraphy for ≥2 weeks documenting adequate habitual sleep (≥7 hours/night) — this is critical to exclude insufficient sleep syndrome
- Discontinue REM-suppressant medications ≥2 weeks prior (≥5 weeks for fluoxetine due to long half-life):
- SSRIs (fluoxetine, sertraline, paroxetine, escitalopram, citalopram)
- SNRIs (venlafaxine, duloxetine, desvenlafaxine)
- TCAs (clomipramine, amitriptyline, nortriptyline, protriptyline)
- Tramadol
- MAOIs
- Discontinue stimulants ≥2 weeks prior (modafinil, methylphenidate, amphetamines)
- Urine drug screen on day of study to confirm medication discontinuation and absence of recreational drugs
- Preceding nocturnal PSG must show:
- ≥6 hours total sleep time
- No untreated severe OSA (AHI >30) that could confound results
- MSLT protocol:
- 5 nap opportunities at 2-hour intervals starting 1.5-3 hours after morning awakening
- Each nap opportunity lasts 20 minutes; extended to 35 minutes if sleep onset occurs (to evaluate for SOREMP)
- Record sleep latency and presence of REM sleep for each nap
- IH-diagnostic result: Mean sleep latency ≤8 minutes with fewer than 2 SOREMPs (0 or 1)
- If ≥2 SOREMPs: reclassify as narcolepsy type 2
- If mean latency >8 min with <2 SOREMPs: does not meet MSLT criteria for IH (consider 24-hr PSG for total sleep time criterion)
APPENDIX B: Low-Sodium Oxybate (Xywav) Prescribing Guide for IH¶
REMS Program Requirements (Same as Narcolepsy Indication): - Prescriber, pharmacy, and patient must all be enrolled in the Xywav REMS program - Distributed only through central pharmacy (Jazz Pharmaceuticals) - Patient must sign acknowledgment of risks
Dosing Protocol for IH: 1. Starting dose: 4.5 g/night divided into 2 equal doses 2. First dose: 2.25 g at bedtime (in bed, ready for sleep) 3. Second dose: 2.25 g taken 2.5-4 hours later (set alarm) 4. Titrate: Increase by 1.5 g/night (0.75 g per dose) every 1-2 weeks 5. Effective range: 6-9 g/night 6. Maximum dose: 9 g/night
Critical Safety Instructions: - Prepare both doses before bedtime; place second dose at bedside - Do not take within 2 hours of eating (food delays absorption) - Do not take with alcohol or other CNS depressants - Allow ≥6 hours between second dose and any activity requiring alertness - Store in secure location out of reach of others (abuse potential) - Monitor for sleepwalking, confusion, respiratory depression - Lower sodium content (92% less than Xyrem); preferred formulation for IH
IH-Specific Considerations: - Xywav is the only FDA-approved medication for IH (approved July 2021) - In IH, Xywav uniquely reduces total sleep time and improves sleep inertia in addition to reducing EDS - Patients with severe sleep inertia may benefit most from Xywav (addresses the most functionally impairing aspect of IH) - Monitor for adequate second-dose awakening — severe sleep drunkenness may impair ability to wake for the second dose; consider assistance from household member