Early sleep onset, late diagnosis
Diagnostic delay is a common problem for patients with narcolepsy. Although the median age of onset is 16 years, a patient typically does not receive the appropriate diagnosis until adulthood. “It takes, on average, somewhere between 8 and 12 years for a patient to get a diagnosis of narcolepsy,” said Dr. Thorpy. Growing awareness and an increase in the number of sleep disorder centers have reduced but not eliminated the diagnostic delay.
Children with narcolepsy are often misdiagnosed. “One of the most common misdiagnoses in childhood is ADHD, because sleepiness in children differs from that in adults,” said Dr. Thorpy. Sleepy children often become hyperactive and display increased impulsivity, he explained. Stimulants prescribed for ADHD tend to mask the symptoms of narcolepsy and delay the correct diagnosis. Mood disorders, behavioral disorders, and psychogenic disorders are other common misdiagnoses for children with narcolepsy.
But when it comes to adults, sometimes patients themselves contribute to the diagnostic delay. EDS is “such a pervasive feeling that I think a lot of people just don’t make much of it,” said Dr. Scammell. The symptom is easily ascribed to insufficient sleep or a difficult work schedule. “It may take them months to get to see a doctor,” said Dr. Scammell.
Behavioral treatments
Nonpharmacologic treatments are one component of care for patients with narcolepsy. Patients must maintain a regular sleep-wake schedule and ensure that they are in bed for no less than 8 hours per night, said Dr. Thorpy. Taking no more than two daytime naps of less than 20 minutes each can help relieve some of the sleepiness, he added.
In addition to ensuring an adequate amount of sleep, it is important to promote good quality sleep, said Dr. Scammell. To do this, clinicians should address any conditions such as sleep apnea that disrupt patients’ sleep, he added.
Patients also tend to avoid situations that are likely to entail the emotional stimuli that could precipitate cataplexy. Some avoid laughter or try to suppress their emotions. “That’s not good,” said Kiran Maski, MD, MPH, assistant professor of neurology at Harvard Medical School and neurologist and sleep physician at Boston Children’s Hospital. “We worry that that might be a risk factor for depression or social isolation.” Cognitive-behavioral therapy can help patients with narcolepsy gradually increase their comfort with and exposure to social situations.
Although behavioral treatments are helpful, they are not sufficient to control all the symptoms of narcolepsy. Most patients require pharmacologic treatments, which are the most effective treatments for narcolepsy, said Dr. Thorpy.
Pharmacologic treatments
Previously, neurologists relied on the stimulants methylphenidate and amphetamine, which primarily treated patients’ EDS. But the field is moving away from these drugs because of their tendency to induce side effects and their potential for abuse, said Dr. Thorpy. In this context, modafinil and armodafinil became the mainstay for promoting alertness in patients with narcolepsy.
In recent years, newer medications have emerged that have slightly greater efficacy and better safety profiles than modafinil and armodafinil. Solriamfetol (Sunosi, Jazz Pharmaceuticals), for example, is effective for EDS but does not affect cataplexy. Pitolisant (Wakix, Harmony Biosciences), on the other hand, effectively treats EDS and cataplexy.
Sodium oxybate (Xyrem, Jazz Pharmaceuticals) is the only medication that treats all the symptoms of narcolepsy, said Dr. Thorpy. “That treats the sleepiness, the cataplexy, and the disturbed nocturnal sleep,” he added. Sodium oxybate also appears to reduce sleep paralysis, hallucinations, and disturbed dreams.
A potential concern about sodium oxybate, which has been used since approximately 2000, is its high sodium load. A new formulation called low-sodium oxybate (Xywav, Jazz Pharmaceuticals) “has a slightly better safety profile, particularly in people who have cardiovascular or renal disease,” said Dr. Thorpy. “This is tending to take over the role of regular sodium oxybate.”
Many clinicians who treat patients with narcolepsy develop their own approaches, but the choice of treatment generally depends on the patient’s symptoms, said Dr. Scammell. Modafinil is a good first choice for patients with mild to moderate sleepiness, he added. Pitolisant is another good choice for these patients but is more expensive. Both drugs are well tolerated.
Clinicians can consider solriamfetol and amphetamine for patients with moderate to severe sleepiness. “I generally consider the oxybates to be a second line,” said Dr. Scammell. Although these drugs may be the most effective, and they do help patients a great deal, they have a higher prevalence of side effects and are more expensive, he added. “If we can get good results with something gentle and simple like modafinil, that would be great.”
“There are differences of opinion as to what the first-line treatments are,” said Dr. Thorpy. Some patients prefer to use the traditional stimulants as first-line treatments, but others prefer to avoid them because of their adverse effects. They favor the newer, and unfortunately more expensive, medications instead. But there is no consensus among clinicians about which of the newer medications to use. “There’s no standard treatment, and it’s very hard to develop an algorithm that is acceptable to most physicians treating patients with narcolepsy,” said Dr. Thorpy. Treatment response varies, as well. Some patients respond extremely well to treatment, but clinical trials indicate that even optimal therapy helps patients achieve about 70% of the normal level of alertness. “If they’re sedentary, sitting in a boring meeting or at the computer, they can still fall asleep, even with our current medications,” said Dr. Scammell.
“The hardest symptom of all to treat is the EDS,” agreed Dr. Thorpy. Most patients cannot be treated with one medication alone, and polypharmacy tends to be necessary, he added. Typically, this means the addition of another medication to the regimen to maximize alertness. For other patients, cataplexy is difficult to control, and adding an anticataplectic medication is appropriate. Still, most patients can control their cataplexy with one drug, either oxybate or pitolisant, said Dr. Thorpy.