Hypersomnia

What Causes Hypersomnia?

Hypersomnia can be caused by many medical problems, stressors, mental health-related issues, medication side effects, and lifestyle habits. Common causes include:

• Stress
• Schedule disruptions (due to work, travel, etc.)
• Poor sleep habits
• Anxiety or depression
• Mental health issues such as post-traumatic stress disorder (PTSD)
• Medications, including antidepressants, high blood pressure medications, asthma medications, and over-the-counter stimulants
• Chronic pain
• Digestive disorders
• Degenerative neurological disorders such as Alzheimer’s or Parkinson’s disease
• Sleep apnea
• Substance use (e.g., nicotine, caffeine, alcohol)
• Hormonal changes (e.g., menopause, thyroid disease, menstruation)

In some cases, the cause of hypersomnia isn’t apparent. These cases are called idiopathic hypersomnia.

Is Hypersomnia Hereditary?

In most cases, hypersomnia is caused by external factors, medical disorders, or other underlying conditions other than genetics. However, studies have suggested that some people have a genetic predisposition to sleep disorders such as hypersomnia, and the predisposition may be inherited. In addition, about one-third of people with hypersomnia have a close relative who has also experienced the problem. This suggests that a genetic component plays at least some role in developing the disorder.

Researchers have not yet identified any specific gene or genetic mutation positively associated with hypersomnia.

How Is Hypersomnia Detected?

Many people experience fatigue or tiredness during the day for various reasons. However, hypersomnia differs from chronic fatigue or lack of energy.

Warning signs of hypersomnia include:

• Falling asleep during the day, even in the middle of activities such as eating or having a conversation
• Napping often and not feeling refreshed upon waking
• Sleeping for a long time at night despite also sleeping during the day

How Is Hypersomnia Diagnosed?

Doctors may take several different diagnostic steps when a patient is experiencing difficulty staying awake.

• Physical exam. A basic physical exam will screen for indications of medical conditions that could be causing the sleep problems.
• Blood tests. The doctor may order laboratory blood tests to rule out conditions, such as thyroid dysfunction, that may be causing hypersomnia.
• Sleep diary. Your doctor may ask you to keep a sleep log over two weeks to look for patterns in your sleep behavior. You may also be asked to track other habits that could impact your sleep, such as caffeine use.
• Sleep study. A study of your sleep patterns, which may be conducted at a sleep center, may be recommended if your doctor suspects that a condition such as sleep apnea could be the cause of your hypersomnia.

The Diagnostic and Statistical Manual of Mental Disorders (DSM) includes diagnostic criteria providers can use to diagnose hypersomnia. The criteria include:

• The patient experiences excessive daytime sleepiness despite getting at least seven hours of sleep.
• The patient falls asleep several times during the day, feels tired after getting more than nine hours of sleep, or doesn’t feel alert when awakened.
• The symptoms occur at least three times a week for at least three months.
• The symptoms cause significant impairment or distress.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Hypersomnia Treated?

Treatment for hypersomnia varies according to its underlying cause. In some cases, hypersomnia resolves with the treatment of an underlying medical condition or the removal of a stressor causing sleep difficulty.

Doctors may prescribe medication to treat hypersomnia when lifestyle changes and changes in sleep behavior don’t relieve symptoms. Some medications commonly prescribed for hypersomnia include:

• Xywav. This combination of calcium, magnesium, potassium, and sodium oxybates has been approved by the FDA to treat hypersomnia and narcolepsy.
• Stimulants such as amphetamine, methylphenidate, and modafinil
• Clonidine, a blood pressure medication
• Dopamine-boosting medications, including bromocriptine and levodopa
• Monoamine oxidase inhibitor antidepressants

How Does Hypersomnia Progress?

Untreated hypersomnia can lead to a wide variety of medical problems, quality-of-life complications, and mental health-related issues, including:

• Problems at work or school
• Relationship difficulties
• Accidents caused by fatigue or mental fogginess
• Anxiety or depression

How Is Hypersomnia Prevented?

There is no known way to prevent hypersomnia, but good sleep habits and a healthy lifestyle can help lessen symptoms. Steps you can take to ensure better sleep include:

• Stick to a regular sleep schedule (even on weekends)
• Don’t eat or drink close to bedtime
• Avoid stimulating activities (e.g., watching TV, using electronics) 30 minutes before bedtime
• Use your bedroom only for sleep
• Keep your bedroom dark and cool
• Get plenty of exercise
• Limit consumption of caffeine and alcohol
• Quit smoking
• Don’t take naps
• Avoid night-shift work
• Try meditation or relaxation techniques

Hypersomnia Caregiver Tips

Some people with hypersomnia also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with hypersomnia:

• Hypersomnia is sometimes associated with neurological disorders such as multiple sclerosis, myotonic dystrophy, or Parkinson’s disease.
• Epilepsy may cause hypersomnia.
• Mood disorders such as bipolar disorder may be associated with hypersomnia.
• The brain condition encephalitis can cause hypersomnia.
• People with hypersomnia are at increased risk of depression and anxiety.

Hypersomnia Brain Science

Scientists are not sure what causes many cases of hypersomnia, but research has suggested that at least some cases are caused by a problem related to a brain chemical called gamma-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter, a chemical whose job is to inhibit the transmission of signals in nerve cells. GABA is essential in keeping the nervous system functioning properly. It regulates the signals passed between nerve cells and prevents inappropriate and unwanted activity in all parts of our bodies.

Studies have shown that some people with hypersomnia experience the effects of over-active GABA. Something in their nervous system (scientists aren’t yet sure exactly what) makes their nerve cells more sensitive than usual to GABA, and that over-sensitivity might be causing their bodies to shut down and fall into a sleep state when they shouldn’t.

Hypersomnia Research

Title: A Phase 3 Study to Assess the Safety and Efficacy of Pitolisant in Adult Patients With Idiopathic Hypersomnia

Stage: Not Yet Recruiting

Contact: Salvatore Insana, PhD

Harmony Biosciences, LLC 

The primary objective of this study is to evaluate the safety and efficacy of pitolisant compared with placebo in treating excessive daytime sleepiness (EDS) in patients with idiopathic hypersomnia (IH) age ≥18 years.

This is a double-blind, placebo-controlled, randomized withdrawal study in adult patients (ages ≥18 years) with IH. The study will consist of a Screening Period (up to 28 days), an 8-week Open-Label Phase, and a 4-week Double-Blind Randomized Withdrawal Phase.

The Open-Label Phase of the study will be eight weeks, including a 6-week Dose Optimization Period and a 2-week Stable Dose Period. In the Dose Optimization Period, all patients will be titrated to their optimal dose of open-label pitolisant (17.8 mg or 35.6 mg) based on the investigator’s assessment of tolerability and efficacy. The 3-week titration period will be followed by three weeks of flexible dosing (weeks 4-6), during which patients will continue to receive their optimal dose of 17.8 mg or 35.6 mg open-label pitolisant. Patients taking a strong CYP2D6 inhibitor will be allowed in the study; however, for these patients, the maximum permitted daily dose of pitolisant will be 17.8 mg. Following completion of the 6-week Dose Optimization Period, patients will enter the 2-week Stable Dose Period. During this period, patients will remain at their optimal dose (the same dosage they were taking at the end of the Dose Optimization Period [17.8 mg or 35.6 mg]) of open-label pitolisant for two weeks; dose adjustments are not allowed during the Stable Dose Period. At the end of the Stable Dose Period, patients will be defined as responders or non-responders. Responders will be randomized in a 1:1 ratio to receive a blinded study drug (pitolisant or matching placebo) in the Double-Blind Randomized Withdrawal Phase of the study. Non-responders will not be randomized to treatment in the Double-Blind Randomized Withdrawal Phase and will complete two safety follow-up telephone contacts (TCs) at 15 (±3) days and 30 (+3) days after their final dose of open-label pitolisant.

During the Double-Blind Randomized Withdrawal Phase, patients (approximately 64 patients per treatment group) will receive a blinded study drug at the same dose they were taking in the Stable Dose Period (17.8 mg or 35.6 mg pitolisant) or a matching placebo. The duration of the Double-Blind Randomized Withdrawal Phase will be four weeks (weeks 9-12); dose adjustments are not permitted during this phase of the study. After completion of the Double-Blind Randomized Withdrawal Phase (End-of Treatment [EOT], on Day 84, the last day of blinded treatment), patients will complete two safety follow-up TCs with the site at 15 (±3) days and 30 (+3) days after their final dose of blinded study drug, which will include assessment for AEs and concomitant medication use; alternatively, patients will have the opportunity to enroll in a long-term, open-label safety study under a separate protocol. Patients who opt to enroll in the long-term, open-label study will not complete the 15-day and 30-day follow-up TCs.

Title: Modafinil Versus Amphetamines for the Treatment of Narcolepsy Type 2 and Idiopathic Hypersomnia

Stage: Recruiting

Principal investigator: Lynn Marie Trotti, MD, MSc

Emory University

Atlanta, GA

For diseases that cause excessive daytime sleepiness (such as narcolepsy and idiopathic hypersomnia), several medications can be used to treat sleepiness. However, it can be difficult to decide which medication to use for a particular individual for several reasons: 1) there are very few studies that directly compare two medications to see which works best; 2) there are very few studies that include people with a disorder of sleepiness called idiopathic hypersomnia.

To address this knowledge gap, the researchers propose a randomized clinical trial comparing modafinil and amphetamine salts in patients with narcolepsy type 2 or idiopathic hypersomnia. All participants will either receive modafinil or amphetamine salts — no participant will receive a placebo.

This study will evaluate which medication works better to improve sleepiness. The researchers will also see which medication is better for other symptoms, including difficulty waking up and difficulty thinking, as well as seeing which medication causes fewer side. Finally, this study will see if any information about patients (such as age or sleep study features) predicts responding better to one medication.

Title: Clinical Trial of Solriamfetol for Excessive Sleepiness Related to Shift Work Disorder

Stage: Recruiting

Principal investigator: Charles A Czeisler, PhD, MD

Brigham and Women’s Hospital

Boston, MA

Shift work has become increasingly common as the 24/7 global society has required more and more workers to do their jobs at irregular hours. According to the National Health Interview Survey in 2010, approximately 28.7% of the American workforce is engaged in work outside a regular day shift (outside 7 AM to 6 PM). Working irregular hours poses a serious threat to the shift worker’s physical, mental, and psychosocial health due to circadian misalignment and misplaced sleep. The most severe problems shift workers face are sleep disturbances and excessive sleepiness. The disruptions caused by shift work are recognized as a circadian rhythm sleep disorder in the International Classification of Sleep Disorders, 3rd Edition, called Shift Work Disorder [SWD]. SWD is characterized by excessive sleepiness (ES) during wakefulness, accompanied by a reduction of total sleep time and/or insomnia. Several studies have shown that 10-43% of shift workers are diagnosed with SWD, dependent on the criteria used.

Studies have shown that wake-promoting agents can be used to treat ES in shift workers, ranging from caffeine to prescription pharmacological agents. Current Food and Drug Administration (FDA) approved options for SWD patients with ES are modafinil and armodafinil. A three-month, double-blind trial of 209 randomized SWD patients showed that modafinil improves wakefulness and the ability to sustain attention working night shifts without negatively affecting daytime sleep. Furthermore, SWD patients who received modafinil had an improvement in clinical symptoms and reduced levels of sleepiness during the night shift and commute home. Proportionally fewer patients reported motor vehicle accidents or near-accidents while commuting home. Czeisler and colleagues also performed a 12-week randomized, double-blind, placebo-controlled, parallel-group, multicenter study, which showed that armodafinil was well-tolerated and improved clinical conditions, wakefulness, attention, and memory during night shifts in SWD patients without jeopardizing daytime sleep and reduced sleepiness during the commute home.

These previous studies described SWD patients working night shifts, yet approximately three times as many individuals work shifts starting in the early morning compared with those who work night shifts. These early-morning shift workers are a unique, high-risk group because their early work start times (3:00 AM to 6:00 AM) require the workers to wake up in the middle of the night, close to their circadian nadir, resulting in curtailed sleep and commuting to work during times of high sleepiness. Previous research has shown that early-morning shift starts, in particular, are associated with increased sleepiness. To the investigators’ knowledge, no studies have addressed the use of wake-promoting agents for ES in early-morning shift workers.

In this clinical trial, the investigators will test whether Solriamfetol (SUNOSITM), a drug approved for the treatment of ES in patients with obstructive sleep apnea (OSA) and narcolepsy, is effective in: (1) decreasing sleepiness without reducing sleep duration or sleep quality; (2) improving work functioning; and (3) improving quality of life in early-morning shift workers diagnosed with ES associated with SWD.