Today, our focus will be on hypersomnolence disorders. This post will delve into narcolepsy and hypersomnolence disorder, along with exploring medical and psychiatric conditions, medications, and substances that may contribute to hypersomnolence.
Today's Content Level: All levels (Beginner, Intermediate, Advanced)
Overview of Hypersomnias
•Hypersomnias are a collection of sleep disorders characterized by excessive daytime sleepiness or extended sleep duration despite sufficient (or excessive) nighttime rest.
Hypersomnolence is a broad term and includes:
Excessive sleep quantity (e.g., extended nocturnal sleep or involuntary daytime sleep)
Deteriorated wakefulness quality (i.e., difficulty awakening or inability to remain awake when required)
Sleep inertia (i.e., impaired performance and reduced vigilance after waking from sleep or a nap)
•Narcolepsy is a chronic neurological disorder characterized by the brain’s inability to regulate sleep-wake cycles.
•Narcolepsy is associated with the loss of neurons in the hypothalamus that produce
hypocretin (a.k.a. orexin), a brain chemical regulating sleep, appetite, and arousal. This condition may involve an autoimmune process, where genetics and environmental factors contribute to the destruction of hypocretin neurons.
It is characterized by excessive daytime sleepiness and falling asleep at inappropriate times. You may also see cataplexy, hypnogogic or hypnopompic hallucinations, and sleep paralysis.
Cataplexy: Intense emotions can cause sudden muscle weakness, often linked to brief episodes of bilateral muscle tone loss. Narcolepsy has two main subtypes: Type 1 (with cataplexy) and Type 2 (without cataplexy).
Hypnogogic and hynopompic hallucinations: Occur during the transitional state between wakefulness and sleep (hypnogogic = when going to sleep; hypnopompic = when popping awake). They involve all senses and can include visual, auditory, tactile, olfactory, and taste sensations. Linked to narcolepsy, sleep paralysis, and insomnia. They are generally harmless and fade as a person fully awakens. Factors like stress, sleep deprivation, and certain medications can increase their frequency and intensity.
Sleep paralysis: Phenomenon where a person is temporarily unable to move or speak when falling asleep or waking up. It can be distressing, with feelings of pressure on the chest, a presence in the room, fear, and anxiety. It may involve hallucinations like seeing shadowy figures or feeling touched.
Hallucinations and/or sleep paralysis at the beginning or end of sleep episodes are common, but not necessary for diagnosis in the DSM-5.
DSM-5 criteria
Recurrent episodes of need to sleep, lapsing into sleep, or napping during the day, occurring ≥ 3 times per week for ≥ 3 months associated with ≥1 of the following:
Episodes of cataplexy.
Hypocretin deficiency in the CSF.
Reduced REM sleep latency on polysomnography (i.e. rapidly enters REM sleep upon falling asleep).
Multiple narcolepsy subtypes are listed in the DSM-5 based on presence or absence of cataplexy, hypocretin deficiency, specific DNA mutations, ataxia, secondary to another medical condition, and timing/duration of symptoms. See DSM-5 for full details.
•Epidemiology: Narcolepsy with cataplexy affects approximately 0.02–0.04% of the global population, with a slightly higher prevalence in males than females. It usually begins during adolescence or early adulthood, with rare cases occurring in older adults. The condition tends to be most severe when it starts suddenly in children.
Assessment: The diagnosis is confirmed following a nocturnal sleep study / polysomnography (PSG) with negative results AND a multiple sleep latency test (MSLT) with positive findings.
PSG: The device monitors various physiological indicators during sleep, including EEG (brain electrical activity), ECG (cardiac parameters), EOG (eye movements), and surface EMG (movement of facial and leg muscles). Video recording is done throughout the night to detect sleep-related medical conditions like sleep apnea, limb movements, and parasomnias. PSG is used to rule out other sleep disorders in narcolepsy cases.
MSLT: The MSLT is started in the morning, connecting the patient to an EEG, EOG, EMG, and ECG (same as polysomnography), and placing them in a dark room to nap and awakening them within 15 minutes. This cycle is repeated 4-5 times during the day. A diagnosis of narcolepsy is based on falling asleep within the 15-minute episodes and observing REM sleep intrusion in at least 2 nap sessions. Narcolepsy is characterized by REM sleep intrusion, leading to hypnagogic hallucinations and sleep paralysis.
•Hypocretin deficiency can be confirmed by testing CSF hypocretin-1 levels. This test is valuable for individuals suspected of conversion disorder without typical cataplexy or when treatment has failed.
Treatment
Lifestyle adjustments: practicing good sleep hygiene (refer to day #154), taking scheduled daytime naps, and avoiding shift work.
Excessive daytime sleepiness: There is no definitive recommendation on the choice of wake-promoting medications to prescribe. Armodafinil (Nuvigil) and modafinil (Provigil) are dopamine reuptake inhibitors approved by the FDA for treating excessive sleepiness linked to narcolepsy, OSA, or shift-work disorder. Other stimulants like methylphenidate, dextroamphetamines, and lisdexamfetamine are also utilized. Sodium oxybate (discussed below) is another option. Although newer medications such as pitolisant (Wakix) and solfiamfetol (Sunosi) are now accessible, they are less commonly used due to limited data and experience, as well as higher costs.
Cataplexy: Sodium oxybate is a form of gamma hydroxybutyrate (GHB) that has the most substantial evidence for alleviating narcoleptic cataplexy and can also help with excessive daytime sleepiness. Research suggests it may enhance slow-wave (delta wave) sleep, potentially improving the quality of restorative sleep. However, its use requires close monitoring due to the risk of diversion and abuse. It is classified as a schedule III drug and is solely available through a controlled distribution program. While it is uncommon for general psychiatrists to prescribe this medication, sleep specialists often utilize it. Additionally, antidepressants (TCAs, SNRIs, SSRIs) have been employed in managing cataplexy.
•Hypersomnolence disorder, also known as idiopathic hypersomnia, is characterized by excessive daytime sleepiness even after extended periods of nighttime sleep, without the presence of sleep paralysis, cataplexy, or disrupted nocturnal sleep cycles typically associated with narcolepsy.
DSM-5 criteria
Excessive sleepiness despite at least 7 hours of sleep, with ≥1 of the following:
Recurrent periods of sleep within the same day.
Prolonged, nonrestorative sleep >9 hours.
Difficulty being fully awake after awakening.
Occurs ≥3 times per week for ≥3 months.
Causes clinically significant distress or impairment in functioning.
Does not occur exclusively during the course of another sleep-wake disorder and is not better explained by the effects of a substance/medication or coexisting mental/medical disorders.
•Symptoms: Around 80% experience nonrestorative sleep, and as many have difficulties awakening in the morning. Around 36-50% experience sleep inertia, showing signs of confusion, impaired alertness, combativeness, ataxia, or impaired performance upon awakening. Short naps (<30 minutes) are typically unrefreshing. Patients may also display automatic behaviors (performing routine tasks without much recollection).
•Epidemiology: Idiopathic hypersomnia is a rare condition, more prevalent in individuals at sleep disorder clinics (5–10%) than in the general population (0.01–0.02%). It affects men and women equally, usually appearing in early adulthood, possibly with a genetic link inherited in an autosomal dominant manner.
•Assessment: PSG may show prolonged sleep duration, but the sleep architecture is typically normal. MSLT demonstrates excessive sleepiness but without the presence of REM sleep intrusions (early-onset REM sleep). Actigraphy is helpful for tracking long periods of sleep in real-life settings and can provide objective data rather than relying solely on patient reports.
Treatment:
Lifestyle adjustments: It is essential to make lifestyle changes such as improving sleep hygiene and incorporating scheduled naps in order to preserve functionality.
Excessive daytime sleepiness: Just like narcolepsy, armodafinil, modafinil, methylphenidate, and amphetamines are first-line pharmacotherapies. Atomoxetine is also sometimes used. Antidepressants can be used to manage mood disturbances associated with the disorder.
Hypersomnia Due to Other Medical Conditions, Substances, or Medications
•Hypersomnia and excessive daytime sleepiness may be secondary to a number of medical or psychiatric conditions, medications, or substances. Below we will discuss some potential causes.
Medical and psychiatric conditions
Breathing-related disorders: the most common of the hypersomnias and include obstructive sleep apnea, central sleep apnea, obesity hypoventilation syndrome. These will be covered on day #158.
Restless legs syndrome and periodic limb movement disorder (day #157)
Narcolepsy (already discussed above)
Depressive disorders and bipolar disorders (during a depressive episode)
Chronic fatigue syndrome
Traumatic brain injury
Autoimmune disorders, e.g., hypothyroidism, lupus, rheumatoid arthritis.
Metabolic disorders, e.g., diabetes mellitus, chronic kidney disease.
Neurodegenerative conditions, e.g., Alzheimer's disease, Parkinson's disease, and multiple system atrophy.
Other neurological disorders, e.g., multiple sclerosis.
Infections, e.g., mononucleosis (EBV), HIV, post-viral syndromes.
Congestive heart failure
Anemia
Kleine-Levin Syndrome is a rare condition characterized by recurrent episodes of hypersomnia, along with behavioral changes, cognitive impairment, hyperphagia, or hypersexuality. Episodes can last days to weeks, and patients may sleep up to 20 hours a day.
Substances
Alcohol
Opioids
Benzodiazepines
Cannabis
Gamma-hydroxybutarate (GHB)
Inhalants (e.g. toluene or nitrous oxide)
Stimulant withdrawal (cocaine, amphetamines, methamphetamine)
"Crash” after using MDMA
Medications
Sedatives and hypnotics (benzodiazepines, ZZZ drugs)
Sedating antidepressants (tricyclic antidepressants, mirtazapine, trazodone, paroxetine)
Antipsychotics
Antihistamines
Anticonvulsants (gabapentin, pregabalin, topiramate, valproate)
Opioids
Muscle relaxants
Some beta blockers
Conclusion
•Hypersomnias encompass a variety of disorders, each with distinct clinical presentations and diagnostic criteria, yet unified by excessive sleepiness. Accurate diagnosis requires a thorough clinical history, sleep studies, and, in some cases, specialized tests like MSLT and CSF hypocretin levels. Management typically involves a combination of pharmacological treatments (stimulants, modafinil, and antidepressants) and non-pharmacological interventions (sleep hygiene and other lifestyle changes).
•In the upcoming lesson, we will cover parasomnias.
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