Sleep Bulletin: Diagnosis and Treatment Options for Narcolepsy and Idiopathic Hypersomnia

Sleep 2023, a joint meeting of the American Academy of Sleep Medicine and the Sleep Research Society, was held in Indianapolis, IN on June 3-7. Although much noteworthy research was presented at this meeting, there was increased attention on 2 sleep disorders: 1) narcolepsy and 2) idiopathic hypersomnia (IH). Dr. Bogan, a specialist in sleep medicine, recently communicated with Practical Neurology about diagnosis and treatment options for narcolepsy and IH.

Why Are Narcolepsy and IH Receiving Increased Attention in the Literature?

Narcolepsy and IH are receiving increased attention, because oftentimes IH is misdiagnosed as narcolepsy due to some symptom overlap between the 2 disorders, mainly with excessive daytime sleepiness symptoms. However, IH is a distinct disorder with its own identifying characteristics. IH is more than excessive daytime sleepiness---symptoms including sleep inertia and long, unrefreshing naps can be felt by patients day and night. As a result, there has been research to better understand the disorder as some physicians believe that IH is simply another form of narcolepsy.¹

What Should Clinicians Look for in Differentiating Narcolepsy from IH?

When differentiating narcolepsy from IH, physicians should look for key identifying characteristics and symptoms of each disorder. Narcolepsy is characterized by excessive daytime sleepiness, irresistible sleepiness (also known as “sleep attacks”), difficulty staying awake, cataplexy (present in type 1 narcolepsy but not in type 2), disrupted nighttime sleep, sleep-related hallucinations, and sleep paralysis. Although there is some symptom overlap with narcolepsy, namely excessive daytime sleepiness, IH is differentiated by the presence of severe sleep inertia, also known as sleep drunkenness, and long, unrefreshing naps. Other IH symptoms include non-restorative sleep, cognitive impairment, and long sleep duration.^1,2

How Many People Are Affected by Narcolepsy and IH?

An estimated 1 in 2000 people in the United States have narcolepsy, but the actual number could be even higher as narcolepsy often can go undiagnosed. For IH, approximately 37,000 adults in the United States have been diagnosed and are actively seeking care for this disorder. This low number may be due to the many difficulties in identifying and diagnosing IH as well as distinguishing it from other similar sleep disorders.²

How Are These Conditions Diagnosed?

Narcolepsy and IH can be diagnosed through different noninvasive sleep tests conducted at a sleep clinic, laboratory, or even at home along with a detailed patient history including sleep history. Standard diagnostic tests include a polysomnography or PSG test, in which a computer records patients’ brain waves, blood oxygen levels, heart rate, breathing, and eye and leg movements as they sleep. There’s also a multiple sleep latency test, or MSLT, which measures how quickly a patient falls asleep during the day and monitors how quickly and how often the patient enters rapid eye movement sleep, also known as REM sleep. In addition, an actigraphy test may be conducted in which a device is worn on the wrist to monitor sleep wake time over a specific period.

What Are the Current Treatment Options for These Conditions?

Narcolepsy and IH are lifelong neurologic conditions for which there is no cure; they often require long-term treatment. Medicines used to treat symptoms of these disorders include stimulants or wakefulness-promoting agents, depressants and sedatives. There are medicines approved to treat symptoms associated with narcolepsy, such as Nuvigil (armodafinil; Cephalon, Malvern, PA), Provigil (modafinil; Cephalon, Malvern, PA), Sunosi (solriamfetol; Axsome Therapeutics, New York, NY), Wakix (pitolisant; Harmony Biosciences, Plymouth Meeting, PA) and Xyrem (sodium oxybate; Jazz Pharmaceuticals, Dublin, Ireland). However, there is only one approved product in the United States for IH. Other therapies are being investigated to treat the underrecognized disorder.³

Xywav (mixed-salt oxybate; Jazz Pharmaceuticals, Dublin, Ireland) oral solution is another approved medicine that can help treat cataplexy and/or excessive daytime sleepiness associated with narcolepsy. It is the first and only therapy approved by the Food and Drug Administration (FDA) for treating adults with IH. Xywav is a low-sodium oxybate and is comprised of a unique composition of cations resulting in 92% less sodium, or a reduction of approximately 1000 to 1500 mg/night, from sodium oxybate. This reduction is clinically meaningful according to various health organizations, including the American Heart Association, National Academies of Sciences, Engineering, and Medicine, and US Department of Health and Human Services.

People living with narcolepsy or IH have higher prevalence of cardiovascular comorbidities, and sodium intake is a risk factor for these heart conditions. According to data presented at the 2023 Annual Meeting of the American Academy of Neurology, patients diagnosed with narcolepsy who were treated with high-sodium oxybate had a higher risk of new-onset hypertension diagnosis or antihypertensive medication initiation within 180 days of starting therapy when compared to a matched control group of patients with narcolepsy not being treated with high-sodium oxybate. In fact, the risk for those taking high-sodium oxybate was approximately twice that of the control group. As a result, having a low-sodium option is important for patients’ long-term health.⁴

Another treatment for narcolepsy recently approved by the FDA is Lumryz (high-sodium oxybate; Avadel Pharmaceuticals, Dublin, Ireland) which is an extended-release version of high-sodium oxybate.

What Are the Key Take-Home Messages for Clinicians Treating Someone with Narcolepsy or IH?

One of the key takeaways physicians should be mindful of when treating patients living with narcolepsy and IH is balancing patient care and/or convenience with their overall health. Based on previous and more recent literature, it has been observed that patients with narcolepsy and IH are at an increased risk of cardiovascular and metabolic comorbidities including stroke, high blood pressure, heart attack and/or failure, obesity and diabetes. A key factor in developing cardiometabolic comorbidities is sodium consumption, so it’s important that neurologists are cognizant of their patients’ sodium intake levels and understand how medications may affect their patients’ risk.

Thus, when determining how best to manage patients’ symptoms, particularly when considering sodium oxybate treatments and agents that increase sympathetic tone, clinicians should be mindful of the cardiometabolic risks their patients face and any existing comorbidities they may have to determine the best approach.

What are Patients Looking for in Terms of Treatment?

Patients are typically looking to treat their tiredness and often say, “I’m tired of being tired.” Excessive sleepiness impacts not only alertness but also executive central nervous system function, speed of mental processing, mood and fatigue. These impairments adversely affect quality of life at work, school, and social life. By improving excessive daytime sleepiness, these impairments improve or hopefully normalize and improve quality of wakefulness.

What’s on the Horizon in the Field of Sleep?

Some exciting research on the horizon is around orexin-2 receptor agonists. Orexins, also known as hypocretins, are neuropeptides that play an important role in regulating sleep and wakefulness. Researchers have determined that the loss of orexin-producing neurons causes narcolepsy type 1 in humans, which may provide an opportunity for novel therapeutic approaches to activate orexin signaling and treat sleep disorders, including narcolepsy and IH. Current therapies only target neurotransmitters downstream from orexin.

Final Thoughts

If you expect that one of your patients may be living with either narcolepsy or idiopathic hypersomnia, it is important to take a detailed patient history, including sleep history, and have your patient undergo either a PSG or MSLT to ensure they receive an accurate diagnosis as soon as possible. These sleep disorders are debilitating and lifelong, so it is vital that people with these conditions receive treatment options that consider their long-term health.