Idiopathic Hypersomnia (IH) is considered a rare sleep disorder. The primary symptom is excessive daytime sleepiness (EDS) that is not improved, regardless of how much time is spent asleep. IH is a chronic disorder that remits in less than 1 in 6 cases, and that responds poorly to traditional treatments. It often negatively impacts upon the patient’s life to such an extent that working, socializing and even driving eventually become impossible due to an inability to sustain vigilant wakefulness.
The most common symptoms shared by sufferers of IH are:
- Greater than 10 hours sleep per 24 hour period – often as much as 16+ hours per 24 hour period
- Long, unrefreshing naps that typically last several hours
- Awakening from sleep feeling unrefreshed, often with significant sleep inertia (commonly known as ‘sleep drunkenness’)
- An inability to be woken from sleep – even multiple alarm clocks or physical attempts made by family/friends are largely unsuccessful.
- Cognitive problems caused by the overwhelming desire to sleep (commonly referred to as ‘brain fog’)
As the condition progresses less common symptoms can include:
- Anxiety and depression – often as a result of the limits this disorder imposes upon what the patient is able to do with their limited time awake
- Raynaud’s type phenomena – freezing cold hands and feet
- Loss of impulse control – especially in regard to food
Those with IH often describe themselves as experiencing two types of sleepiness:
- A physical exhaustion that ‘normal’ people might experience after missing several nights sleep in a row.
- A cognitive exhaustion similar to Executive Dysfunction that can make even simple tasks like reading, conversation with friends, or watching a movie beyond their reach.
IH is a diagnosis of exclusion. This means that doctors look for other common causes that they might surmise account for hypersomnia. Because most of these efforts lead to ‘dead ends’, and there is no consensus knowledge between doctors of what factors can lead to hypersomnia, a diagnosis often takes many years after the initial symptoms appear. A formal diagnosis is rendered only after chronic or acute insufficient sleep, primary sleep disorders (e.g., obstructive sleep apnea) are excluded with an overnight sleep study, and manifest sleepiness is confirmed by objective means the day following this sleep study (e.g., Multiple Sleep Latency Test (MSLT)).
Unlike narcolepsy (with cataplexy), the overnight sleep study of an IH patient will often show a perfectly normal night sleep that is highly efficient (i.e., the patient sleeps for > 95% of the time allotted for the test). The MSLT is used to rule out narcolepsy, with IH patients falling asleep quickly but not entering rapid-eye movement (REM) (or dream sleep) in their naps. For those with IH the urge to sleep can be resisted to some extent before becoming totally overwhelming, and they are unlikely to fall asleep without warning. A diagnosis of IH requires at least 360 minutes of total sleep time the night before an MSLT demonstrates an average latency to sleep on 4 or 5 daytime naps that is < 8 minutes, and fewer than 2 naps in which REM-sleep is entered. That being said, the MSLT is neither specific nor sensitive for a diagnosis which can be unsettling to many doctors. That is, many “normal” individuals exhibit such a profile, and many subjects known to suffer from IH may not exhibit these features when they are tested. Thus, a better diagnostic test for IH that is more faithful to the biology that “causes” its symptoms, is needed.
Currently there are no treatments approved by medicine regulatory agencies available specifically for Idiopathic Hypersomnia. The traditional treatments used are normally prescribed either “off-label” or through purposeful ‘misdiagnosing’ of patients as having genuine narcolepsy, ADHD, or depression, in order that 3rd party carriers will assume the cost of treatments. The most common treatments prescribed are:
- Amphetamines (such as Dextroamphetamine® or Adderall®)
- Methylphenidate (such as Ritalin® or Concerta®)
- Modafinil (such as Provigil® or Modavigil®)
- Armodafinil (such as Nuvigil® or Waklert®) (Currently unavailable in Australia)
- Sodium Oxybate (such as Xyrem®) (Currently unavailable in Australia)
Unfortunately, patients with IH often respond incompletely to the traditional treatments. Often increasingly larger doses are needed and it commonly reaches a point where negative side effects outweigh the benefits.
Recent Research Since the classification of IH in the mid-1900’s very little progress has been made towards understanding the mechanism of action in the patient that might create these symptoms. This all changed late in 2012. A recent paper from researchers at Emory University suggests that the sleepiness of those with IH might be caused by hypersensitivity in their brain to the amino acid known as GABA. [Rye et al, 2012]
The GABA system is well understood as the primary neurotransmitter responsible for sleep. Many medications have thus been formulated to purposefully manipulate this system. For example, common sleeping pills, such as benzodiazepines and related compounds such as zolpidem (Ambien®), and general anaesthetics, such as propofol, are effective because they function to turn up the gain of the brain’s GABA systems (viz., they work as agonists at specialized receptors that are activated/engaged by GABA).
The research suggests that the brains of patients with Idiopathic Hypersomnia are hypersensitive to GABA and they are experiencing the same effects a ‘normal’ person might experience if they on a continuous dose of sleeping pills or a mild general anaesthetic. It is possible for patients to fight this tiredness/fatigue for a while, but in the medium to long term it becomes impossible for them to function. Rather than being a ‘sleep disorder’ per se, it might then be more appropriate to consider IH as a ‘wakefulness disorder’ where the patient is chemically unable to stay awake for long periods or think clearly during their time awake.
Interestingly, the researchers at Emory University found a similar hypersensitivity to GABA in patients diagnosed with other sleep disorders including narcolepsy without cataplexy. They and other investigators postulate that IH and narcolepsy without cataplexy might, in fact, turn out to have more in common than these different designations imply. They may be part of the same spectrum of ‘disorders’ which share in common long sleep periods, sleep drunkenness and persistent sleepiness in contrast to the brief “attacks” of sleep suffered by those with narcolepsy-cataplexy.
This discovery opens up several new possibilities for treatments for patients with IH. Rather than using treatments to try and stimulate the brain to be ‘awake’ it is possible to use medicine to counter the hypersensitivity to GABA. The primary contender is a drug known as Flumazenil. Flumazenil was discovered in the 1980’s, and FDA approved in 1991, for reversing general anaesthetic and reversing sleeping pill over-doses in the ER. Another possible treatment is an antibiotic called Clarithromycin that also appears to reduce the hypersensitivity to GABA.
The researchers at Emory University conducted a small trial with 7 patients suffering from a mixture of patients with IH, narcolepsy without cataplexy, and even some that verifiably slept routinely for 10-14 hours/day, but whose MSLTs were otherwise considered ‘normal’. They administered Flumazenil through their veins and recorded a significant improvement in wakefulness in the patients. They have since conducted a double-blind, placebo controlled, cross-over clinical trial with 20 patients using Clarithromycin and once again, recorded a significant improvement in wakefulness.
While it is too early to suggest that Flumazenil or Clarithryomycin might become standard treatments for IH, it is nonetheless promising and refreshing to see new research uncovering fresh options. As further trials are conducted and more patients with IH are found to respond, or not respond, this information will serve to help future patients in returning to a more normal life.
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