Primary Hypersomnia Differential Diagnoses

  • Author: Adrian Preda, MD; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych(UK)  more...
Updated: Jan 09, 2015

Diagnostic Considerations

Before making a diagnosis of hypersomnolence, consider the following:

  • Is there a temporal relationship between the onset, exacerbation, and remission of the hypersomnia and its associated features/conditions
  • Is there a family history of hypersomnia versus associated features (a general medical condition, depression, etc.)

In addition, carefully consider factors such as age of onset, typical versus atypical features, and course. Such determinations should help in differentiating among the following entities.[1, 22, 23]

Normal sleep variation

"Long sleepers" (i.e., individuals with a greater than average sleep duration) do not present with excessive daytime sleepiness, sleep drunkenness, or automatic behaviors as long as they obtain their regular amount of sleep.[1] An understanding of the individual’s sleep baseline is required before making a diagnosis.

Chronic insufficient sleep

The nocturnal sleep duration should be qualified as adequate before a diagnosis of idiopathic hypersomnia is made. An average sleep duration of less than 7 hours can result in excessive daytime sleepiness similar in presentation to hypersomnolence. If this is suspected, patients should be instructed to document their sleep duration in sleep diaries. Often, an improvement in daytime symptoms is noted following an increase in sleep duration. When in doubt, a sleep extension trial can be prescribed for 10-14 days to clarify the diagnosis.[1]

Substance-induced sleep disorder, hypersomnia type

This should be diagnosed if hypersomnia is secondary to the use or abuse of prescription medications, over-the-counter drugs, or illicit drugs. Of note, hypersomnia can be a direct result of using a specific drug (e.g., benzodiazepines, antihistamines) or can occur as a result of stopping a previously used/abused drug (e.g., stimulants, cocaine). When in doubt, a drug screen can help to clarify the diagnosis.

Upper airway resistance syndrome (breathing-related sleep disorder)

This syndrome is associated with excessive daytime sleepiness and heavy snoring causing frequent arousals during nocturnal sleep. Obesity is common; patients may have anatomic abnormalities of the upper airway, such as a high, narrow, arched palate; malocclusion of the mouth; or retrognathia.

Polysomnographic recording shows short alpha-electroencephalogram arousals lasting 3-5 seconds. Monitoring esophageal pressure or quantifying airflow using a pneumotachometer is required to confirm the presence of this syndrome. The use of nasal continuous positive airway pressure as a therapeutic test can help to confirm the diagnosis.

Posttraumatic hypersomnia

Posttraumatic hypersomnia may mimic hypersomnolence. Symptoms usually develop 6-18 months after head trauma.

Other neurologic disorders

Imaging studies of the brain may identify a communicating hydrocephalus or brain tumor with daytime hypersomnolence as the presenting symptom/chief complaint, in the absence of any other neurologic signs or symptoms.

Hypersomnia secondary to other general medical conditions

Excessive daytime hypersomnia also may occur from frequent chronic pain or from repeated awakenings because of an underlying medical disorder.

As the use of medications can result in hypersomnia, a careful history and chronology of the symptoms are necessary to clarify the underlying cause. In the hospital, especially in intensive care units, hypersomnia may also be secondary to a disruption of the sleep-wake cycle or, in severe cases, may reflect an underlying delirium due to a general medical condition.

Major depressive disorder

Hypersomnia may be the presenting feature of primary depression, which should be excluded by performing a careful psychiatric evaluation. To complicate matters further, patients with primary hypersomnia are at increased risk of developing a major depressive disorder. Therefore, all patients with hypersomnia should receive a careful mental status and psychiatric evaluation for depression. The purpose of the psychiatric evaluation is to determine if there are dynamic family, work, or interpersonal issues that may cause or contribute to the depression.

Characteristic symptoms include depressed mood, anhedonia (a loss of interest and pleasure), decreased energy, psychomotor agitation or retardation, decreased or increased appetite (which may result in weight loss or gain), decreased attention and concentration, decreased libido, feelings of guilt or worthlessness, and, in severe cases, suicidal ideation, delusional thought processes, or auditory hallucinations.

The most common sleep disturbance reported in melancholic depression is poor sleep. Sleep disturbances such as difficulty in sleep initiation and sleep maintenance and/or early awakening are common. Subsequent daytime tiredness resulting in frequent or prolonged naps may be mistaken for excessive daytime sleepiness.

Hypersomnia associated with increased appetite, weight gain, mood reactivity (meaning the mood brightens in response to positive events), leaden paralysis (ie, a leaden feeling in the arms or legs), and rejection sensitivity is characteristic of atypical depression.

If depression is present, a careful history clarifying the chronology of symptoms (did hypersomnia precede or follow the associated depressive symptoms) is required to clarify the primary diagnosis.


Excessive daytime sleepiness, a history of cataplexy, and the presence of sleep-onset REM periods should allow the differentiation of narcolepsy from idiopathic hypersomnia. In the absence of cataplexy, the disorder may be difficult to differentiate. A diagnosis of narcolepsy requires the presence of 2 or more sleep-onset REM periods on the Multiple Sleep Latency Test, as well as association with the human leukocyte antigen (HLA)-DR15 and HLA-DQ6 haplotype.

By contrast, patients with primary hypersomnia usually present with longer and less interrupted nocturnal sleep, have more difficulties waking up, and have more sleepiness during the daytime (rather than the more discrete "sleep attacks" in narcolepsy).

Primary hypersomnia patients also have longer and less refreshing daytime sleep episodes, with little or no dreaming during daytime naps (as opposed to the sleep-onset REM periods seen in narcolepsy).[1]

Circadian rhythm sleep disorders

Delayed sleep phase syndrome is a diagnostic consideration in some patients whose main complaints are extreme difficulty awakening at a desired time and excessive morning sleepiness. An abnormal sleep-wake schedule (with shifted or irregular hours) is often present in individuals with circadian rhythm sleep disorder.[1] These patients do not have excessive daytime sleepiness in the latter half of the day and are not able to fall asleep until late at night.

Other psychiatric disorders

Hypersomnia associated with dysthymia and related mood disorders is observed frequently. The presentation is usually later in life. A low-grade chronic depression and an inability to cope with stressful situations are observed. The sleep disturbance in psychiatric patients with the chief complaint of hypersomnia appears to be associated with a centrally driven hyperarousal, whereas primary hypersomnia is associated with a centrally driven hypoarousal. Multiple Sleep Latency Test findings do not demonstrate short sleep latency.

Persistent or relapsing fatigue that does not resolve with bedrest characterizes chronic fatigue syndrome. Polysomnographic recording shows reduced sleep efficiency and alpha intrusion into sleep on electroencephalogram (EEG).

Differential Diagnoses

Contributor Information and Disclosures

Adrian Preda, MD Professor of Clinical Psychiatry and Human Behavior, Director of Residency Program in Psychiatry, Vice-Chair, Department of Psychiatry and Human Behavior, University of California, Irvine, School of Medicine

Adrian Preda, MD is a member of the following medical societies: American Association for the Advancement of Science, American Psychiatric Association, International College of Neuropsychopharmacology, International Congress of Schizophrenia Research, Schizophrenia International Research Society, Society of Biological Psychiatry

Disclosure: Nothing to disclose.

Chief Editor

Iqbal Ahmed, MBBS, FRCPsych(UK) Faculty, Department of Psychiatry, Tripler Army Medical Center; Clinical Professor of Psychiatry, Uniformed Services University of the Health Sciences; Clinical Professor of Psychiatry, Clinical Professor of Geriatric Medicine, University of Hawaii, John A Burns School of Medicine

Iqbal Ahmed, MBBS, FRCPsych(UK) is a member of the following medical societies: Academy of Psychosomatic Medicine, American Neuropsychiatric Association, American Society of Clinical Psychopharmacology, Royal College of Psychiatrists, American Association for Geriatric Psychiatry, American Psychiatric Association

Disclosure: Nothing to disclose.


Jennifer S Morse, MD Associate Medical Director, Optum Health

Jennifer S Morse, MD is a member of the following medical societies: Academy of Psychosomatic Medicine, Aerospace Medical Association, and American Psychiatric Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. American Psychiatric Association. Primary hypersomnia. Diagnostic and Statistical Manual of Mental Disorders. Text Revision (DSM-IV-TR). 4th Edition. Washington, DC: American Psychiatric Association; 2000. 604-9.

  2. American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic - coding manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005.

  3. Dement W, Rechtschaffen A, Gulevich G. The nature of the narcoleptic sleep attack. Neurology. 1966 Jan. 16(1):18-33. [Medline].

  4. Roth B, Nevsimalova S, Rechtschaffen A. Hypersomnia with "sleep drunkenness". Arch Gen Psychiatry. 1972 May. 26(5):456-62. [Medline].

  5. Roehrs T, Zorick F, Sicklesteel J. Excessive daytime sleepiness associated with insufficient sleep. Sleep. 1983. 6(4):319-25. [Medline].

  6. Billiard M. Diagnosis of narcolepsy and idiopathic hypersomnia. An update based on the International classification of sleep disorders, 2nd edition. Sleep Med Rev. 2007 Oct. 11(5):377-88. [Medline].

  7. Bassetti C, Pelayo R, Guilleminault C. Idiopathic Hypersomnia. Kryger MH, Roth T, Dement WC. Principles and Practices of Sleep Medicine. 4th Edition. Philadelphia, PA: Elsevier; 2005. 791-800.

  8. Roth T. Introduction: narcolepsy and excessive daytime sleepiness: from the bench to the bedside. J Clin Psychiatry. 2007. 68 Suppl 13:4. [Medline].

  9. Guilleminault C. Disorders of excessive sleepiness. Ann Clin Res. 1985. 17(5):209-19. [Medline].

  10. Roth B. Narcolepsy and hypersomnia: review and classification of 642 personally observed cases. Schweiz Arch Neurol Neurochir Psychiatr. 1976. 119(1):31-41. [Medline].

  11. Arnulf I, Zeitzer JM, File J, et al. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain. 2005 Dec. 128(Pt 12):2763-76. [Medline].

  12. Billiard M, Guilleminault C, Dement WC. A menstruation-linked periodic hypersomnia: Kleine-Levin syndrome or new clinical entity?. Neurology. 1975. 25:436-443. [Medline].

  13. Montplaisir J, Poirier G. HLA in disorders of excessive sleepiness without cataplexy in Canada. Honda Y, Juti T. HLA in Narcolepsy. Berlin, Germany: Springer-Verlag; 1988. 186-190.

  14. Guilleminault C, Faull KF, Miles L. Posttraumatic excessive daytime sleepiness: a review of 20 patients. Neurology. 1983 Dec. 33(12):1584-9. [Medline].

  15. Montplaisir J, de Champlain J, Young SN. Narcolepsy and idiopathic hypersomnia: biogenic amines and related compounds in CSF. Neurology. 1982 Nov. 32(11):1299-302. [Medline].

  16. Kanbayashi T, Kodama T, Kondo H, Satoh S, Inoue Y, Chiba S, et al. CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome. Sleep. 2009 Feb 1. 32(2):181-7. [Medline]. [Full Text].

  17. Nishino S, Okuro M, Kotorii N, Anegawa E, Ishimaru Y, Matsumura M, et al. Hypocretin/orexin and narcolepsy: new basic and clinical insights. Acta Physiol (Oxf). 2009 Jun 25. [Medline]. [Full Text].

  18. Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. Sleep Med Rev. 2005 Aug. 9(4):269-310. [Medline].

  19. Yamanaka A, Tsujino N, Funahashi H, Honda K, Guan JL, Wang QP, et al. Orexins activate histaminergic neurons via the orexin 2 receptor. Biochem Biophys Res Commun. 2002. 290:1237-45. [Medline]. [Full Text].

  20. Ohayon MM, Dauvilliers Y, Reynolds CF 3rd. Operational Definitions and Algorithms for Excessive Sleepiness in the General Population: Implications for DSM-5 Nosology. Arch Gen Psychiatry. 2012 Jan. 69(1):71-9. [Medline].

  21. Guilleminault C, Faull KF. Sleepiness in nonnarcoleptic, non-sleep apneic EDS patients: the idiopathic CNS hypersomnolence. Sleep. 1982. 5 Suppl 2:S175-81. [Medline].

  22. Bassetti C, Gugger M, Bischof M. The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A). Sleep Med. 2003 Jan. 4(1):7-12. [Medline].

  23. Ohayon MM. From wakefulness to excessive sleepiness: what we know and still need to know. Sleep Med Rev. 2008 Apr. 12(2):129-41. [Medline].

  24. Sangal RB; Mitler MM; Sangal JM. Subjective sleepiness ratings (Epworth sleepiness scale) do not reflect the same parameter of sleepiness as objective sleepiness (maintenance of wakefulness test) in patients with narcolepsy. Clin Neurophysiol. Dec 1999. (110)12:2131-5. [Medline].

  25. Sangal RB, Sangal JM, Belisle C. Subjective and objective indices of sleepiness (ESS and MWT) are not equally useful in patients with sleep apnea. Clin Electroencephalogr. 1999 Apr. 30(2):73-5. [Medline].

  26. Rechtschaffen A, Roth B. Nocturnal sleep of hypersomniacs. Act Nerv Super (Praha). 1969. 11(3):229-33. [Medline].

  27. Anderson KN, Pilsworth S, Sharples LD, Smith IE, Shneerson JM. Idiopathic hypersomnia: a study of 77 cases. Sleep. 2007 Oct 1. 30(10):1274-81. [Medline].

  28. [Guideline] Morgenthaler TI, Kapur VK, Brown T, Swick TJ, Alessi C, Aurora RN, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007 Dec 1. 30(12):1705-11. [Medline].

  29. Ballon JS, Feifel D. A systematic review of modafinil: Potential clinical uses and mechanisms of action. J Clin Psychiatry. 2006 Apr. 67(4):554-66. [Medline].

  30. Valentino RM, Foldvary-Schaefer N. Modafinil in the treatment of excessive daytime sleepiness. Cleve Clin J Med. 2007 Aug. 74(8):561-6, 568-71. [Medline].

  31. Schwartz JR. Modafinil: new indications for wake promotion. Expert Opin Pharmacother. 2005 Jan. 6(1):115-29. [Medline].

  32. Poppe M, Friebel D, Reuner U, Todt H, Koch R, Heubner G. The Kleine-Levin syndrome - effects of treatment with lithium. Neuropediatrics. 2003. 34:113-9. [Medline].

Primary hypersomnia. Polysomnographic study demonstrates apnea (absence of carbon dioxide fluctuation indicating no flow), chest wall paradox, abrupt increase in tidal volume at the end of apnea, and oxygen desaturation. All of these features are consistent with obstructive sleep apnea.
Primary hypersomnia. In contrast to obstructive sleep apnea, mixed apnea shows absence of respiratory efforts in the first segment of the apnea.
Primary hypersomnia. Periodic limb movements show intermittent leg electromyogram activity accompanied by electroencephalogram arousals.
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