A new American Academy of Sleep Medicine clinical practice guideline details “strong” and “conditional” recommendations for the treatment of central disorders of hypersomnolence in adults and children.

By Lisa Rapaport

It’s been more than a decade since the American Academy of Sleep Medicine (AASM) last issued guidelines for the treatment of central disorders of hypersomnolence, sleep disorders characterized by excessive daytime sleepiness despite sufficient or even excessive hours of sleep at night. New AASM recommendations released in August 2021 on medications to treat these disorders—which include narcolepsy, idiopathic hypersomnia, and Kleine-Levin Syndrome—cover several therapies that weren’t yet approved when the previous guidelines came out.

Two new medications—solriamfetol and pitolisant—were approved by the US Food and Drug Administration (FDA) in 2019 and are now strongly recommended by the AASM for treating narcolepsy in adults. In the latest guidelines, the AASM also conditionally recommends sodium oxybate for treating narcolepsy in children; this drug was approved by the FDA in 2018 for use in children who are at least 7 years of age.

“The prior set of treatment recommendations was published in 2007,” says Lynn Marie Trotti, MD, MSc, an associate professor of neurology at Emory University School of Medicine in Atlanta. Trotti is on the board of directors at the AASM and co-authored the new hypersomnolence recommendations. “A lot has changed in the narcolepsy and hypersomnia treatment landscape since that time.”

A result of all these changes is the AASM for the first time made graded recommendations for or against medications for specific adult and pediatric central disorders of hypersomnolence. A “strong” recommendation in the new guidelines means most patients will benefit from treatment and clinicians should generally follow this advice, while a “conditional” recommendation means evidence of safety and effectiveness is more nuanced and requires clinicians to consider individual patient’s values and preferences to determine the best course of treatment.

“The biggest implication of this change is that we were not able to make any recommendation for some interventions that have been widely used in clinical practice and were recommended in the 2007 guideline, such as antidepressants for the treatment of cataplexy,” Trotti says. “Importantly, the absence of a recommendation doesn’t imply that these medications should not be used, just that we found insufficient evidence to make a recommendation.”

With the new graded recommendation system, the AASM also emphasizes clinical significance over statistical significance in evaluating treatments. This gives providers actionable information to help them determine when a treatment is likely to have a meaningful effect for individual patients, Trotti says.

For adult patients with narcolepsy, the AASM strongly recommends modafinil, pitolisant, sodium oxybate, and solriamfetol. The guidelines also conditionally recommend armodafinil, dextroamphetamine, and methylphenidate.

Modafinil is also strongly recommended for adults with idiopathic hypersomnia. For this condition, clarithromycin, pitolisant, and sodium oxybate are conditionally recommended. The first-ever FDA approved treatment for idiopathic hypersomnia, Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution was approved in August 2021, after the new AASM guidelines were completed.

Lithium is conditionally recommended for adults with Kleine-Levin syndrome.

The AASM conditionally suggests clinicians use armodafinil or modafinil to treat hypersomnia secondary to traumatic brain injury in adults.

For adults for whom hypersomnia is secondary to other medical conditions, the guidelines conditionally recommend armodafinil when adult patients have dementia with Lewy bodies, and modafinil or sodium oxybate when adults have Parkinson’s disease.

Modafinil is also conditionally recommended for adults with genetic disorders associated with primary central nervous system hypersomnolence and adults with hypersomnia secondary to brain tumors.

For pediatric patients with narcolepsy, the guidelines conditionally recommend modafinil and sodium oxybate.

All of the recommendations for modafinil note that it’s a federally controlled substance due to the potential for abuse and dependency. Modafinil has also been linked to fetal harm in animal studies, and this drug as well as armodafinil have been linked to congenital abnormalities.

Modafinil, armodafinil, and pitolisant may reduce the effectiveness of oral contraceptives, the guidelines also note.

Another recommended medication, sodium oxybate, has a FDA black box warning because it can cause respiratory depression. Sodium oxybate is the sodium salt of gamma hydroxybutyrate, a controlled substance due to the potential of abuse or misuse and the risk of respiratory depression, coma, and death especially when used in combination with alcohol or sedating medications.

Because of the strength of the evidence supporting medications for different indications varies, and because some side effects and risks may be more problematic for patients with specific health conditions or at specific stages in their lives, clinicians need to carefully consider which medication may be optimal on a case by case basis, says Marie-Pierre St-Onge, PhD, CCSH, FAHA, associate professor and director of the Sleep Center of Excellence at the Columbia University Irving Medical Center in New York City, who was not involved in writing the new guidelines.

Patients at high risk for drug dependency or who are suspected of potential drug misuse, for example, should not be prescribed modafinil, according to St-Onge. Nor should women who are pregnant or trying to conceive, due to the fetal risks, or women on oral contraceptives unless they take other precautions to avoid pregnancy, St-Onge adds.

“Clinicians should also consider other comorbidities such as the risk of cardiovascular disease, allergies, and adverse events and re-evaluate treatment choice and efficacy regularly,” advises St-Onge.

Marie Nguyen Dibra, MD, a sleep specialist at Sleep Dallas who was not involved in writing the guidelines, also emphasizes that hypersomnia patients should be screened for potential risks before medications are prescribed. “Since many of the medications we use to treat hypersomnolence (alerting agents and stimulants) can cause adverse side effects such as anxiety, palpitations, increased blood pressure, or worsening hypertension, it’s important to screen and counsel patients with pre-existing anxiety, coronary artery disease, and hypertension about these potential risks,” she says. “Alerting agents such as Provigil [modafinil] and Nuvigil [armodafinil] can decrease effectiveness of oral contraceptives, making it important to discuss this with patients to avoid unexpected pregnancy. They can also interact with Plavix, an essential medication for patients with certain cardiac conditions, so patients should always update their providers with the most recent drug/medication lists.” 

Ideally, clinicians should reassess medication decisions annually, says Nancy Foldvary-Schaefer, DO, MS, director of the Cleveland Clinic Sleep Disorders Center and a professor of neurology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Ohio, who was not involved in writing the new guidelines. This should include a discussion of any new diagnoses or comorbidities, the effectiveness of any current medications, patient’s treatment goals, and the cost and affordability of drugs.

One advantage of these regular reassessments is that clinicians may be able to switch patients to medications with fewer side effects, better efficacy, or lower out-of-pocket costs.

“With new drugs available, there is an opportunity in most patients to optimize outcomes and reduce the impact of traditional stimulants on cardiovascular health,” Foldvary-Schaefer says.

But medications shouldn’t be the only treatment clinicians consider for hypersomnolence, says Kiran Maski, MD, MPH, chair of the AASM task force and a pediatric neurologist and sleep specialist at Boston Children’s Hospital. Clinicians should also consider additional non-pharmacologic measures as part of the treatment plan, including sleep hygiene, work or school accommodations, and cognitive behavioral therapy, Maski says in a statement about the paper.

Even so, choosing the optimal medication can help make a profound difference for many patients, Maski says.

“Central disorders of hypersomnolence are rare neurological disorders that can affect safety, work or school functioning, and social relationships due to crippling daytime sleepiness, fatigue, and impaired attention,” Maski says. “The AASM guideline will help clinicians determine the best treatment options for their patients to improve excessive daytime sleepiness, disease severity, and quality of life.”

Lisa Rapaport is a freelance journalist with experience writing and editing news about health, medicine, wellness, and science.


Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 17(9);1 Sept 2021:1881-93.

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