III. History

  1. History of Sleepiness
  2. Comorbid significant medical conditions (e.g. Neurologic Disorders)
  3. Medications (including non-prescription items, supplements and Herbals)
  4. Alcohol and other Drugs of Abuse
  5. Mood and emotional stressors
  6. Lifestyle, night-time work hours, and sources of sleep deprivation
  7. Sleep habits (including Insomnia, snoring, and possible Sleep Apnea)
  8. Restless Leg Syndrome

IV. Screening: Significant Daytime Somnolence indicating additional evaluation

  1. Falling asleep while driving OR
  2. Epworth Sleepiness Scale >12

V. Differential Diagnosis

  1. Insomnia (Disorder of Initiating and Maintaining Sleep or DIMS)
    1. Insomnia typically causes paradoxical daytime hyperarousal instead of Sleepiness
    2. Insomnia with excessive Daytime Sleepiness suggests comorbidity (e.g. Sleep Apnea)

VI. Labs

VII. Diagnostics: Sleep Study

  1. Step 1: Overnight Polysomnography evaluates for Sleep Apnea
    1. Positive: Treat Sleep Apnea
    2. Negative: Perform step 2 testing
  2. Step 2: Polysomnography evaluates sleep onset latency (time to fall asleep)
    1. Multiple Sleep Latency Test (MSLT)
      1. Hypersomnolence with early onset REM Sleep diagnoses Narcolepsy without cateplexy
    2. Maintenance of Wakefullness Test (MWT)
      1. Assess waking performance in alertness-critical professions (e.g. drivers, pilots)

VIII. Management: General

  1. Treat underlying cause (e.g. Sleep Deprivation, Sleep Apnea, Restless Legs Syndrome)
  2. Practice Sleep Hygiene and ensure adequate sleep time

IX. Management: Stimulant Medications

  1. See Narcolepsy for specific management
  2. Contraindications
    1. Untreated Sleep Apnea
    2. Other secondary causes not fully excluded
    3. Mild or unproven Hypersomnolence
    4. Recent vascular event (CVA, MI) or multiple Cardiovascular Risk Factors
    5. Arrhythmia
    6. Uncontrolled Hypertension
  3. Adverse Effects
    1. Headache
    2. Nausea
    3. Anxiety
  4. Indications
    1. Excessive Sleepiness despite appropriate Obstructive Sleep Apnea management with CPAP
    2. Daytime Sleepiness with Shift Work Disorder
    3. Other moderate to severe excessive Daytime Sleepiness
  5. First-line agents (controlled substance C-IV Agents)
    1. Modafinil (Provigil, generic, roughly $90/month in 2020)
      1. Best safety profile and lowest abuse potential of all stimulant agents
      2. Czeisler (2005) N Engl J Med 353(5): 476-86 [PubMed]
    2. Armodafinil (Nuvigil, generic, roughly $90/month in 2020)
    3. Solriamfetol (Sunosi, expensive at $700/month in 2020)
  6. Novel agents (non-controlled)
    1. Pitolisant (Wakix)
      1. Released in 2020 for Daytime Somnolence for Narcolepsy
      2. Active at CNS histamine receptors and appears to be as effective as Modafinil
      3. However, very expensive ($11,400 per month) andf many Drug Interactions as well as QT Prolongation
      4. (2019) presc lett 27(1):6
  7. Other agents (higher risk of abuse or side effects)
    1. Dextroamphetamine (Dexedrine)
    2. Methylphenidate (Ritalin)
    3. Pemoline (Cylert)
      1. Risk of hepatotoxicity

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Related Studies

Ontology: Drowsiness (C0013144)

Definition (NCI) The sensation of struggling to remain awake.
Concepts Finding (T033)
MSH D012894
SnomedCT 206711009, 79519003, 271782001, 284091004, 158122000
LNC LA16352-9
English Drowsiness, Drowsinesses, SLEEPINESS, DROWSINESS, Somnolence, [D]Drowsiness, [D]Drowsiness (context-dependent category), Drowsiness, function, drowsy, drowsiness, drowsy (physical finding), drowsiness (symptom), drowsiness was observed, sleepiness, somnolence, sleepy, somnolent, Mental status, drowsy, Somnolence (sleepiness), Sleepy, [D]Drowsiness (situation), Sleepy (finding), Drowsy, Sleepiness, Drowsiness, function (observable entity), Drowsy (finding), Drowsiness (function)
Portuguese SONOLENCIA, Sonolento, Sonolência, LETARGIA
Dutch slaperigheid, suf voelen, slaperig, Slaperigheid
French Ensommeillé(e), Endormissement, Envie de dormir, ASSOUPISSEMENT, ENVIE EXCESSIVE DE DORMIR, Somnolence, Assoupissement
German Verschlafenheit, schlaefrig, Schlaefrigkeit, Schläfrigkeit, DOESIGKEIT, SCHLAEFRIGKEIT, Somnolenz
Italian Addormentato, Sonnolenza
Spanish Tendencia al sueño, Soñoliento, Adormecimiento, [D]modorra (categoría dependiente del contexto), Somnolencia, ADORMECIMIENTO, MODORRA, [D]modorra, somnoliento, somnoliento (hallazgo), [D]modorra (situación)
Japanese 眠気, 眠気状態, 傾眠状態, ネムケ, ケイミンジョウタイ, ネムケジョウタイ
Czech Ospalost, Ospalý, ospalost
Hungarian Álmosság, Álmos
Norwegian Søvnighet

Ontology: Fatigue (C0015672)

Definition (CCC) Exhaustion that interferes with physical and mental activities
Definition (MEDLINEPLUS)

Everyone feels tired now and then. Sometimes you may just want to stay in bed. But, after a good night's sleep, most people feel refreshed and ready to face a new day. If you continue to feel tired for weeks, it's time to see your doctor. He or she may be able to help you find out what's causing your fatigue and recommend ways to relieve it.

Fatigue itself is not a disease. Medical problems, treatments, and personal habits can add to fatigue. These include

  • Taking certain medicines, such as antidepressants, antihistamines, and medicines for nausea and pain
  • Having medical treatments, like chemotherapy and radiation
  • Recovering from major surgery
  • Anxiety, stress, or depression
  • Staying up too late
  • Drinking too much alcohol or too many caffeinated drinks
  • Pregnancy

One disorder that causes extreme fatigue is chronic fatigue syndrome (CFS). This fatigue is not the kind of tired feeling that goes away after you rest. Instead, it lasts a long time and limits your ability to do ordinary daily activities.

NIH: National Institute on Aging

Definition (NCI) Overall tiredness and lack of energy.(NICHD)
Definition (NCI) A question about whether an individual has or had a lack of energy.
Definition (NCI_NCI-GLOSS) A condition marked by extreme tiredness and inability to function due lack of energy. Fatigue may be acute or chronic.
Definition (NCI_CTCAE) A disorder characterized by a state of generalized weakness with a pronounced inability to summon sufficient energy to accomplish daily activities.
Definition (NAN) An overwhelming sustained sense of exhaustion and decreased capacity for physical and mental work at usual level
Definition (MSH) The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
Definition (CSP) state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
Concepts Sign or Symptom (T184)
MSH D005221
ICD10 R53.83
SnomedCT 206767001, 206771003, 158169005, 367392001, 302758002, 139126000, 84229001, 248274002
LNC MTHU013358, LA7542-9
French FATIGUE, Fatigue extrême, Perte d'énergie, Energie diminuée, Ereinté, Lassitude, Sensation de manque total d'énergie, EPUISEMENT, FAIBLESSE, LASSITUDE, Fatigue
English FATIGUE EXTREME, TIREDNESS, WEARINESS, [D]Fatigue, [D]Tiredness, [D]Fatigue (context-dependent category), [D]Tiredness (context-dependent category), Extreme fatigue, Decreased energy, decreased energy, fatigue (diagnosis), fatigue, Feeling of total lack of energy, Fatigue extreme, Tired out, Fatigue NOS, Fatigue [Disease/Finding], rndx fatigue (diagnosis), rndx fatigue, lacking energy, fatigues, loss of energy, tired time, tiredness, fatigue extreme, extreme fatigue, weariness, fatigued, tatt, time tired, energy loss, fatiguing, tired all the time, Lacks Energy, [D]Fatigue (situation), [D]Tiredness (situation), Lacking in energy (finding), Tiredness (finding), I have a lack of energy, FATIGUE, Lack Energy, Energy decreased, Tiredness, Lack of energy, Loss of energy, Weariness, Fatigue (finding), Lack of energy (finding), Lacking in energy, Fatigue, Lack of Energy, lack of energy, Lack (of);energy
Portuguese FADIGA, Fadiga extrema, Sensação de falta total de energia, Perda de energia, Exausto, Energia diminuída, CANSACO, ESGOTAMENTO, EXAUSTAO, Fadiga
Spanish FATIGA, Abatimiento, Sensación de falta absoluta de energía, Pérdida de energía, Fatiga extrema, Cansado, Cansancio, Falta de energía, [D]cansancio (categoría dependiente del contexto), [D]fatiga (categoría dependiente del contexto), ABATIMIENTO, CANSANCIO, FATIGA EXTREMA, [D]cansancio (situación), [D]cansancio, [D]fatiga, faltante de energía, faltante de energía (hallazgo), [D]fatiga (situación), cansancio, falta de energía (hallazgo), falta de energía, fatiga (hallazgo), fatiga, pérdida de energía, Fatiga
German ERMUEDUNG, Mangel an Energie, Muedigkeit extrem, Ueberdruss, Energie abgenommen, abgeschlafft, Gefuehl voelligen Energiemangels, Muedigkeit, ABGESCHLAGENHEIT, MUEDIGKEIT STARK, MUEDIGKEIT, Ermuedung, Ermüdung, Müdigkeit
Italian Affaticamento, Affaticamento estremo, Esaurito, Sensazione di totale mancanza di energia, Perdita di energia, Energia ridotta, Stanchezza
Dutch vermoeid, moeheid, uitzonderlijk moe, verlies van energie, gevoel van energieloosheid, energie afgenomen, vermoeidheid, Moeheid
Japanese 活力低下, 活力喪失感, 活力喪失, 疲労困ぱい, 極度の疲労, 疲労, ヒロウコンパイ, カツリョクテイカ, カツリョクソウシツカン, ヒロウ, キョクドノヒロウ, カツリョクソウシツ
Swedish Trötthet
Czech únava, Utahanost, Extrémní únava, Utahaný, Ztráta energie, Úbytek energie, Únava, Vyčerpanost, Pocit celkového nedostatku energie
Finnish Väsymys
Croatian UMOR
Polish Znużenie, Zmęczenie
Hungarian Kimerültség, Defatigatio, Kifáradt, Teljes energiahiány érzete, Energia elvesztése, Fáradtság, Kimerültség, extrém, Csökkent energia
Norwegian Tretthet, Utmattelse, Trøtthet, Fatigue

Ontology: Disorders of Excessive Somnolence (C0020524)

Definition (MSH) Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., IDIOPATHIC HYPERSOMNOLENCE; NARCOLEPSY; and KLEINE-LEVIN SYNDROME) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, MENTAL DISORDERS, and SLEEP APNEA SYNDROME). (From J Neurol Sci 1998 Jan 8;153(2):192-202; Thorpy, Principles and Practice of Sleep Medicine, 2nd ed, p320)
Concepts Disease or Syndrome (T047)
MSH D006970
ICD10 G47.1
SnomedCT 194439006
English Disordrs/excessive somnolence, Disorders of excessive somnolence [hypersomnias], DIS EXCESSIVE SOMNOLENCE, DOES DIS EXCESSIVE SOMNOLENCE, EXCESSIVE SOMNOLENCE DIS, HYPERSOMNOLENCE DIS, DOES (Disorders of Excessive Somnolence), Disorders of Excessive Somnolence, Excessive Somnolence Disorder, Excessive Somnolence Disorders, Somnolence Disorder, Excessive, Somnolence Disorders, Excessive, Hypersomnolence Disorder, Hypersomnolence Disorders, Disorders of Excessive Somnolence [Disease/Finding], DOESs (Disorders of Excessive Somnolence), hypersomnolence disorder, sleep disorder hypersomnolence, hypersomnolence disorder (diagnosis), Disorders of excessive somnolence, Disorder of excessive somnolence, Disorders of excessive somnolence (disorder), hypersomnia type; sleep disorder, sleep disorder; hypersomnia type
Swedish Onormalt stort sömnbehov
Czech poruchy nadměrné spavosti, nadměrná spavost
Finnish Uneliaisuushäiriöt
German Krankhaft gesteigertes Schlafbeduerfnis, Störungen durch ekzessive Somnolenz
Japanese 過眠症, 睡眠過剰症, 睡眠過剰障害, 過剰睡眠障害, 睡眠過剰, 過剰睡眠
Italian DOES (Disturbi della sonnolenza eccessiva), Disturbi da ipersonnolenza, Disturbi della sonnolenza eccessiva
Korean 과다 수면 장애[과면증]
Polish Senność wzmożona, Nadmierna senność, Wzmożona senność
Norwegian Eksessiv somnolensforstyrrelser, Overtretthetsforstyrrelser, Unormalt stort søvnbehov
Spanish Trastornos de Somnolencia Excesiva, Hipersomnia, Trastornos de Excesiva Somnolencia, Hipersomnio, trastornos de somnolencia excesiva (trastorno), trastornos de somnolencia excesiva
Croatian Not Translated[Disorders of Excessive Somnolence]
Portuguese Transtornos da Sonolência Excessiva, Distúrbios do Sono por Sonolência Excessiva
Dutch hypersomnia-type; slaapstoornis, slaapstoornis; hypersomnia-type, Stoornissen met bovenmatige slaperigheid [hypersomnia], Hypersomnie, Slaapzucht
French Troubles du sommeil par somnolence diurne excessive, Troubles du sommeil par somnolence excessive

Ontology: Daytime sleepiness (C0541854)

Concepts Finding (T033)
Dutch slaperigheid overdag
French Somnolence diurne
German Schlaefrigkeit waehrend des Tages
Italian Sonnolenza diurna
Portuguese Sonolência diurna
Spanish Somnolencia diurna
Japanese 日中の眠気, ニッチュウノネムケ
Czech Denní ospalost
English Daytime sleepiness, sleepiness daytime, daytime sleepiness
Hungarian Nappali álmosság

Ontology: Hypersomnolence (C0751229)

Concepts Sign or Symptom (T184)
MSH D006970
Czech hypersomnolence
Portuguese Hipersonolência
Spanish Hipersomnolencia
French Hypersomnolence
German Hypersomnolenz
English hypersomnolence, hypersomnolent, Hypersomnolence
Norwegian Overtretthet, Hypersomnolens
Italian Ipersonnolenza
Dutch Hypersomnolentie

Ontology: Hypersomnia (C0917799)

Definition (NCI_CTCAE) A disorder characterized by characterized by excessive sleepiness during the daytime.
Definition (NCI) A sleep disorder characterized by excessive sleepiness during the daytime.
Definition (PSY) Excessive sleepiness.
Concepts Sign or Symptom (T184)
MSH D006970
ICD9 780.54
ICD10 G47.10 , G47.1
SnomedCT 309732001, 206751007, 158154009, 270961006, 77692006, 230486000, 158149000, 191998008
LNC LP121711-8, MTHU039892, LA15882-6
English Hypersomnias, [D]Hypersomnia NOS, Sleeping Excessive, [D]Hypersomnia (context-dependent category), [D]Hypersomnia NOS (context-dependent category), [D]Hypersomnia, sleeping too much (symptom), sleeping too much, sleeping too much (hypersomnia), hypersomnia, Sleep excessive, Hypersomnia, unspecified, Hypersomnia NOS, increased sleep, much sleeping too, excessive sleep, excessive sleepiness, sleep too much, too much sleep, much sleep too, excessive sleeping, Primary Hypersomnia, Hypersomnia, [D]Hypersomnia (situation), [D]Hypersomnia NOS (situation), Hypersomnia [D], Hypersomnia (excessive sleeping), Hypersomnia NOS (disorder), Excessive sleeping, Sleep too much, Excessive sleep, Excessive sleepiness, Sleeps too much, Hypersomnia (disorder), Hypersomnia, NOS
Dutch slaap overmatig, hypersomnie, Hypersomnia
French Sommeil excessif, Hypersomnie
German exzessiver Schlaf, Hypersomnie
Italian Sonno eccessivo, Ipersomnia, Ipersonnia
Portuguese Sono excessivo, Hipersonia, Hipersónia
Spanish Sueño excesivo, [D]hipersomnia, SAI (categoría dependiente del contexto), [D]hipersomnia (categoría dependiente del contexto), Hipersomnios, [D]hipersomnia, SAI, [D]hipersomnia (situación), hipersomnia, SAI, [D]hipersomnia, SAI (situación), [D]hipersomnia, hipersomnia, SAI (trastorno), somnolencia excesiva, hipersomnia (trastorno), hipersomnia, Hipersomnia
Japanese 睡眠過剰, 過眠症, スイミンカジョウ, カミンショウ
Czech hypersomnie, Nadměrný spánek, Hypersomnie
Hungarian Hypersomnia, Túlzott mértékő alvás
Norwegian Hypersomnia

Ontology: Daytime somnolence (C2219848)

Concepts Sign or Symptom (T184)
SnomedCT 141000119100
English excessive sleepiness during the day (daytime somnolence), daytime somnolence, excessive sleepiness during day, excessive sleepiness during day (symptom), Daytime somnolence (finding), Daytime somnolence
Spanish somnolencia diurna (hallazgo), somnolencia diurna

Ontology: Daytime hypersomnia (C3662832)

Concepts Sign or Symptom (T184)
SnomedCT 31771000119102
English Daytime hypersomnia (disorder), Daytime hypersomnia
Spanish hipersomnia diurna, hipersomnia diurna (trastorno)