Idiopathic hypersomnia (IH) is a chronic neurological condition with symptoms of pathological daytime sleepiness with or without extended sleep durations. It’s difficult to accurately estimate how many people suffer from IH and how often it occurs because of the demand for electrophysiological testing and ruling out other disorders that may cause similar symptoms.
The clinical estimates of IH are limited because of the biases and differing referral patterns. For example, the estimates of relative IH frequency to cataplexy narcolepsy can vary significantly – from 1:10 to more than 1:1. For that reason the true prevalence of IH is unknown.
Ohayon used a questionnaire-based algorithm to demonstrate excessive sleepiness and multiple and irresistible daytime naps, sleep of nine hours that doesn’t rejuvenate, or having problems waking up and found these issues in 0.5 percent of the population. While some people do not meet the diagnostic standards of IH, it’s safe to say that its symptoms are fairly common.
The word idiopathic means unknown; it’s not known where the pathophysiology of idiopathic hypersomnia originates.
Hypocretin deficiency, which causes narcolepsy type 1, is not seen in IH patients. However, the cerebrospinal fluid in IH patients and other central nervous system conditions of hypersomnolence show a rise in activity at the GABA-ZA receptors to excessive amounts. While this rise in GABAergic transmission hasn’t proven to be synched with sleepiness or extended sleep durations in IH patients, there is biological plausibility.
It is also worth noting that some IH patients have reversed their symptoms using GABA-receptor antagonists or negative allosteric modulators.
Up to 38 percent of all IH patients have a family history of excessive sleepiness. With the parent/child transmission of 12.5 percent it appears that one parent of IH patients routinely sleeps around 9.5 or more hours a night. This would mean that IH has some type of genetic tie.
Still, the potent link between HLA DQB*0602 and type 1 narcolepsy is not seen in IH patients where the positivity rate has a range of 8 to 27 percent – population dependent. IH patients may have an immune system dysregulation unique to sufferers from type 1 narcolepsy. This can be noted by extremely high allergic disorders and comorbid inflammatory rates and the modified IgG profile.
IH patients are found to have a disruption in the functioning of the autonomic nervous system with a move to a higher vagal tone. Perhaps this leads to commonly observed symptoms in IH patients such as:
- Raynaud’s syndrome
- Orthostatic hypotension
IH patients have a sleep efficiency of 90 percent or higher, but some studies show mean values in the 80 percentile range. There is some discretion here for the tendency for high sleep efficiency and with the recently-proposed hypothesis that patients with IH have fragmented sleep, as noted by the following:
- More awakenings during an hour
- More N1 sleep
- More changes in the stages of sleep.
All these instances were seen more in IH patients than type 1 narcolepsy patients. There have been some abnormalities in the slow-wave sleep percentages, but nothing consistently observed. In one study there is some thought that the spindle activity increases in IH patients compared to any type of narcolepsy.
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Ancillary IH symptoms
People with IH often suffer from ancillary features such as:
Cognitive function (brain fog)
There have been reports that some IH patients suffer from consistent cognitive dysfunction. 79 percent of IH patients experience memory problems, while 55 percent have attention issues. 58 percent of people feel as if their mind is blank, and 61 percent often make mistakes. A short study shows that IH patients’ cognitive symptoms are significant, but also one in five patients has attention deficit disorder.
IH patients often exhibit signs of sleep drunkenness (difficulty with awakening) when waking up from daytime naps and nocturnal sleep. Nearly half of all IH patients have sleep drunkenness. And treating it can be difficult because of the sufferer’s inability to stay awake for long enough to take the medication that propels wakefulness. A family member must have the stimulant medication ready one hour before scheduled awakening or dose stimulants at bedtime.
Patients are often advised to take melatonin at night to ease sleep drunkenness, but there is very little evidence that this can work.
Prolonged and unrefreshing naps
Naps, just like sleeping for a long time at night, are often long for IH patients. Patients also find that their naps are not restful. And they don’t benefit from any medications or scheduled naps.
Long duration of sleep
Prior ICSD editions clearly lay out a subset of idiopathic hypersomnia as noted by long sleep times (more than 10 hours). While the current standards don’t separate people who sleep for long periods of time from those who don’t, long sleep times are often used to determine if someone has IH.
Some treatment options
IH patients suffer a significant decrease in daytime functioning and the quality of life, even when they follow the treatment plan. It can be a challenge to distinguish a patient with mood dysfunction, IH, and hypersomnia tied to a psychiatric disorder as the symptoms of depression are often seen in IH sufferers and may add even more difficulty to treating their disease.
Support and patient advocacy groups
As with other chronic diseases, patient advocacy and support groups can be extremely beneficial. You can also educate yourself from online, national, and local resources.
An important part of the nonpharmacological aspect of the clinical care for IH patients is safety counseling, which involves two primary things:
- Driving and safety-critical activities
- Medication interactions and side effects.
People who have hypersomnolence such as IH have a higher chance of getting into vehicular accidents. Treatments may not entirely diminish this risk!
Other important safety concerns include the use of power tools and heavy machinery for people with this condition. A look at the maintenance of wakefulness testing (MWT) calculates IH and narcolepsy patients’ on-road driving performance and can be used to make better decisions.
Due to these factors more attention is being paid to using nonpharmacological therapy as a possible treatment for IH sufferers. Most IH patients (around 96 percent) use at least one nonpharmacological method to treat their disease. For example, they may suggest the use of caffeine, daytime naps, and scheduled nocturnal sleep. The problem is that nonpharmacological techniques for IH sufferers have ranked poorly on a scale of one to 10.
While caffeine was regarded as the most effective, nicotine and nocturnal sleep, diet, exercise, daytime naps, chewing gum, yoga, and other treatment options were noted to have low scores too. IH patients have reported nearly all interventions as being fairly ineffective compared to narcolepsy patients in the same study.
In 20 percent of all IH cases there have been spontaneous remissions, but there are no factors that would identify why this happens.
Are there any medications approved for IH treatment?
The U.S. Food and Drug Administration has yet to approve any drug for the use of IH, and until recently there were hardly any printed randomized controlled trials conducted for IH treatment. In 2007 the American Academy of Sleep Medicine came up with a practice parameter before the three IH RCTs had been published.
Modafinil was considered a viable option for the disorder in the practice parameter. That’s because Modafinil had shown a dramatic decrease in drowsiness and sleep attacks in 15 subjects. There were other medications considered for use in the practice parameter too:
However, amphetamines come with warnings about the possibility of abuse, drug diversion, dependence, and cardiovascular side effects. Another concern is the interference of Armodafinil and Modafinil with hormonal birth controls.
In the initial RCT, which was published in 2014, there was a crossover trial that compared placebo and Modafinil to determine the ability to maintain wakefulness on MWT and in an on-the-road driving test. 14 IH patients were included in the sample (27 total). Modafinil was used and found to significantly reduce the number of times patients crossed the line (improving driving safety) compared to placebo. As a result Modafinil can help improve a person’s ability to stay awake and alert, but subjects were still far sleepier than the control group.
In another RCT study there were 33 IH patients who did not suffer from long sleep times. They were given 200mg of Modafinil in two doses, which led to a decrease in subjective sleepiness measured with the Epworth Sleepiness Scale. There was no significant difference between the placebo and Modafinil, but it is worth noting that the Modafinil group saw improvement in their wakefulness.
Treatment resistance problems
Some IH patients did particularly well with monotherapy with a quarter of them suffering from treatment resistant symptoms even when using standard therapies. 58 percent of 85 patients needed just one treatment, and 65 percent of them attained total control over their symptoms. 26 percent saw partial symptom relief, and 9 percent had a negative response.
In another study with less stringent guidelines 72 percent of the patients achieved great control of their symptoms with the use of an unknown stimulant.
54 patients of another study met the ICSD-2 criteria for mean sleep latency. 61 percent responded to combined or monotherapy. 83 percent reported improvement by using only Modafinil. During an internet survey of 129 IH patients medication was only effective half of the time. This was far less than what patients with narcolepsy indicated in the same survey.
For the whole hypersomnolent group – those with either narcolepsy type or IH – the side effects of the medication stopped the consistent use of pharmacotherapy for EDs in 23 percent of patients.
Alternative pharmacological techniques were used in cases of treatment-refractory sleepiness or standard treatment intolerances. There have been a number of medications suggested for IH treatment such as:
- Transcranial direct stimulation
- Nonamphetamine stimulants
- Histamine H3 inverse agonists
- GABA-A receptor antagonists/negative modulators (flumazenil and charithromycin)
- GABA-B/gamma hydroxybutyrate receptor agonists.
The only one to actually be analyzed in IH patients was clarithromycin. In this study 500mg of clarithromycin taken at breakfast and lunch led to improvement in ESS scores and other subjective IH symptom measurements. However, it did not lead to better psychomotor vigilance.
Idiopathic hypersomnia can cause excessive daytime sleepiness and impair overall quality of life. While there are no medications currently on the market to sufficiently control the symptoms, recent work has offered doctors some idea of how to treat their patients with both pharmacological and nonpharmacological methods.
Researchers need to conduct more research. With more knowledge about IH pathophysiology there are some real possibilities of developing more targeted treatments for the condition.
Key points to bear in mind
- Once believed to be a rare condition, idiopathic hypersomnia is not as uncommon as many believe. Still, there is no concrete evidence of how many people suffer from it.
- The first line of treatment of IH is typically Modafinil, which has been supported by two controlled but random trials. IH treatments often consist of psychostimulants, but the information that supports this use is inconsistent.
- Medication intolerance prevents control of symptoms in a quarter of patients. However, there are numerous alternative treatment options available, such as clarithromycin.
- There are no perfect tests for diagnosing IH, and some patients never meet the criteria even though they have problems with sleepiness.
- IH diagnosis demands a look at other conditions that could explain the symptoms (hypersomnolence due to a medical condition, hypersomnolence due to a psychiatric disease, narcolepsy without cataplexy, circadian rhythm disorders, insufficient sleep time).