Optimizing narcolepsy care: Diagnosis, treatment and patient access | Written recap

In a recent Managed Healthcare Executive K-Cast video series, R. Robert Auger, M.D., a psychiatrist and sleep specialist at the Mayo Clinic in Rochester, Minnesota, spoke about the diagnosis and treatment of narcolepsy and idiopathic hypersomnia.

Quality of life

Excessive daytime sleepiness, the cardinal feature of narcolepsy, negatively affects individuals’ quality of life in several ways, Auger explained. It can be embarrassing in social or occupational settings. Safety when driving or operating machinery is a concern. Some patients have sleep attacks that involve falling asleep without any prodromal drowsiness. Some people with narcolepsy experience cataplexy, a sudden bout of muscle weakness that is evoked by pleasurable emotions and can occur during pleasurable recreational activities and sexual intercourse, Auger said.

Types 1 and 2

Both Type 1 and Type 2 narcolepsy are characterized by disabling daytime sleepiness, said Auger. About 60% of narcolepsy cases are Type 1, which is characterized by either cataplexy or low levels of hypocretin, a neurotransmitter involved in the regulation of sleepiness and wakefulness. People with Type 2 narcolepsy have normal levels of hypocretin. “The clinical presentation can be pretty similar because even in patients with Type 1 narcolepsy, oftentimes the sleepiness precedes the emergence of cataplexy, sometimes by even up to four years or longer,” Auger said. Both types require the presence of disabling daytime sleepiness for at least three months to meet the diagnostic criteria.

A history of cataplexy can be hard to document, Auger noted, so if cataplexy is suspected, the results of a multiple sleep latency test can help with the diagnosis. The multiple sleep latency test must show a mean sleep latency of eight minutes or less and two or more REM periods occurring within 15 minutes of sleep onset. In some cases a REM period from a nocturnal sleep study can be factored in.

Autoimmune evidence

There’s an “emerging line of evidence” that suggests an autoimmune process that destructs hypocretin neurons may cause narcolepsy in people with a genetic susceptibility to the disorder, said Auger. He described hypocretin receptor 2 agonists as “very promising, emerging therapies” that could revolutionize treatment, particularly of Type 1 narcolepsy.

Current treatments

Traditionally, narcolepsy was treated with stimulants, including amphetamines and methylphenidate, Auger said. The FDA-approved treatments mentioned by Auger include modafinil (Provigil), armodafinil (Nuvigil), solriamfetol (Sunosi) and pitolisant (Wakix). He also noted that a variety of oxybate formulations are used to treat the condition, including sodium oxybate (Xyrem), a lower-sodium version (Xywav) and an extended-release one (Lumryz).

The oxybate formulations are not typically used as monotherapy for excessive daytime sleepiness. More often, they are used to augment a stimulant response or to address cataplexy directly. Pitolisant has also been shown to be effective for cataplexy, according to Auger, and sometimes just treating sleepiness can mitigate the cataplexy. Auger noted that cataplexy in Type 1 narcolepsy is on a continuum, with some patients experiencing just a drooping of the jaw, slurring of speech and slumping of the shoulders. For others, it can be more disabling and involve the buckling of the knees or a complete physical collapse, sparing only the extraocular and respiratory muscles.

First-line therapy for narcolepsy includes modafinil and armodafinil, according to Auger, who noted that they have been assessed in double-blind, placebo-controlled studies. Modafinil and armodafinil interfere with steroidal contraceptives, he noted, so other types of contraception should be discussed with individuals using steroidal contraception, and switching to barrier methods of contraception considered. Second-line therapy is either pitolisant or solriamfetol, but pitolisant is also contraindicated for patients taking oral contraceptives, Auger said.

After those options are exhausted, and assuming they’re practically available from an insurance standpoint, then traditional stimulants are typically used, usually methylphenidate first, perhaps followed by the amphetamines, said Auger. The oxybates are often used as stimulant-sparing agents, Auger explained. If a patient taking stimulants is experiencing anxiety, headaches or other side effects, lowering the dose could help, along with the oxybates, taken adjunctively.

Modafinil, armodafinil or pitolisant might not be preferred if a patient is unwilling or unable to forgo steroidal contraceptives. Auger said he would lean toward prescribing solriamfetol or the traditional stimulants in those cases. If those medications are poorly tolerated, monotherapy with one of the oxybates or a lower dose of the poorly tolerated stimulant with one of the oxybates would be an option.

For people with both cataplexy and daytime sleepiness, the treatment choices include monotherapy with pitolisant or one of the oxybates or combined therapy with one of the stimulants and sodium oxybate. Clinicians are now recognizing that the lower-sodium content of the low-sodium version of oxybate is notable, particularly for patients who have cardiovascular disease," Auger said.

Idiopathic hypersomnia

Narcolepsy and idiopathic hypersomnia are quite different, Auger explained. “[Idiopathic hypersomnia] almost seems to be a disorder of wakefulness, whereas narcolepsy is more a condition of sleepiness,” he said. People with narcolepsy do not typically sleep more during a 24-hour period than those without narcolepsy; however, people with idiopathic hypersomnia will sleep more during a 24-hour period than those without the condition. Another difference: Naps are often refreshing, albeit temporarily, for people with narcolepsy but for people with idiopathic hypersomnia, naps are unrefreshing, according
to Auger.

People with idiopathic hypersomnia often exhibit strong sleep inertia after arousing from sleep. Low-sodium oxybate is the only medication that’s FDA approved for idiopathic hypersomnia, Auger noted. Low-sodium oxybate seems to have some beneficial effects for sleep inertia, which is often the primary complaint of patients with idiopathic hypersomnia, according to Auger.

Considerations and barriers

Research has shown a significant delay between the onset of symptoms of narcolepsy and diagnosis, Auger said, and lack of access or distance from a tertiary care center can further that delay. Once the condition is identified and stimulant medications are recommended, often primary care providers are not comfortable with prescribing stimulants over the long term, and most institutions will require at least annual in-person visits. With the newer drugs, prior authorization and other insurer requirements create “a lot of clerical burden” with appeal letters and the like, Auger said. These problems play a big role in the management of idiopathic hypersomnia because there’s only one medication that is FDA approved to treat the condition. Particularly for newer medications for which there’s no generic version, there’s invariably a lot of paperwork, insurer denials and appeals. “If someone didn’t have the support that I have in my practice for dealing with those issues, it could almost be a deal-breaker with treating these patients because of the inundation of paperwork and clerical work that’s involved with prescribing [the newer medications],” Auger said.

Reasons for optimism

Auger said telemedicine has made it possible to treat more patients, particularly in rural areas. In addition, preliminary results from the clinical trials of the hypocretin receptor 2 agonists are “very, very promising,” Auger said. Those agents could, he said, “revolutionize the treatment of narcolepsy because [they] would provide, in essence, a cure, whereas all of the treatments that we do presently are just symptomatic treatments.”