Michael Thorpy, MD, discussed current and emergent treatment options available for the sleep disorder in a symposium during the SLEEP 2016 meeting.

Overall goals of narcolepsy treatment include improving the safety of the patient as well as managing symptoms. “The goals of treatment are to get under control the excessive daytime sleepiness, which is usually the main symptom in all patients with narcolepsy. There are other symptoms that patients with narcolepsy have that may need to be controlled as well,” Michael Thorpy, MD, professor of clinical neurology at Albert Einstein College of Medicine in New York, explains in an e-mail interview with Sleep Review. Thorpy presented on the subject at the “Best Practices for Managing Narcolepsy and Obstructive Sleep Apnea: Evidence-Based Strategies and Solutions” symposium on June 13 in Denver, Colo. “Treating narcolepsy is more than just treating excessive sleepiness and cataplexy, but requires management of all the ancillary symptoms of narcolepsy.”

As such, treatment goals may include reducing daytime sleepiness, cataplexy, sleep paralysis, nightmares and hallucinations, and disturbed nocturnal sleep. Thorpy notes that treatment should also enable a patient to function better in life (such as perform better in school, on the job, and socially), as well as improve the safety of the patient and the general public. “Patients with narcolepsy can fall or have sudden sleep episodes that may put them at risk of either a motor vehicle accident or an accident even around the house…particularly if they’re working with any dangerous equipment. Improving not only their symptoms [and] quality of life but also preventing any risk to the patient or to others because of the sleepiness [should be a goal of treatment].”

Current Treatments

During the symposium, Thorpy detailed the specific mechanisms of different alerting agents. These include: caffeine, with the mechanism of adenosine receptor antagonist; modafinil, for which the mechanism is not clear, but appears to be predominately by dopamine; histamine receptor 3 inverse agonists (H3R); hypocretin agonists; and sympathomimetic, which is designed to enhance neurotransmission of dopamine, serotonin, and norepinephrine.

“There are two main types of drugs that one would consider; the drugs that improve alertness and wakefulness during the daytime and those that suppress cataplexy. Then there are other medications that can be used to treat additional narcolepsy symptoms or in order to improve the quality of sleep,” Thorpy says.

There are two important precautions for patients who use modafinil and armodafinil, Thorpy notes: they can reduce oral contraceptives efficacy (they increase the metabolism of ethinylestradiol) and can cause serious rashes and allergic reactions. Of the traditional stimulants, Adderall, a dopamine and norepinephrine-releasing agent, is an additional medication available for managing narcolepsy symptoms. Available in two formulations—instant release (IR) and extended release (XR)—only the IR is indicated for narcolepsy, Thorpy says.

According to Thorpy, sodium oxybate is the only medication that can treat all symptoms of narcolepsy and can improve overall cognitive functioning. This medication has a number of benefits, including reducing vivid dreams, nightmares, and hallucinations; improving nocturnal sleep; and reducing sleep paralysis. “I think that the sodium oxybate is the most appropriate agent for patients who have the diagnosis of narcolepsy because it’s the only drug that treats all the symptoms of narcolepsy. It’s a very effective medication at treating all those symptoms,” he says.

But there are certain precautions for healthcare professionals and users to be aware of with sodium oxybate (although Thorpy says it is well tolerated among most patients). It can cause nausea and headaches. It should not be used with hypnotics, alcohol, or depressant medications. Also, because it has the potential to cause respiratory depression, it should not be prescribed to patients with untreated obstructive sleep apnea. In addition, caution should be exercised with patients who may be depressed, and Thorpy recommends healthcare professionals ask patients about suicidal ideation or previous attempts.

Overall, sodium oxybate is an effective first-line drug for the treatment of narcolepsy for patients with narcolepsy type 1 and 2, and an effectual second-line of treatment should include modafinil or armodafinil for sleepiness and venlafaxine or atomoxetine for cataplexy. Thorpy says the combination of sodium oxybate and modafinil produces the most effective treatment of excessive sleepiness.

“All medications have potential side effects and it’s a matter of weighing out in a particular patient what would be the appropriate medication and the balance between the effectiveness and potential for side effects,” Thorpy says.

On the Horizon

Thorpy also addressed emerging treatments for narcolepsy, which he categorized in two ways: non-hypocretin-based therapies and hypocretin-based therapies. Non-hypocretin-based therapies include monoaminergic reuptake inhibitors, histamiergic H3 antagonist/inverse agonists, monoaminergic stimulating agents, and TRH analogues. Hypocretin-based therapies include peptide agonists, gene therapy, hypocretin cell transplantation, and nonpeptide agonists.

Future narcolepsy treatments may target hypocretin and histaminergic systems, Thorpy says. “Further down the line, we would hope that medications that affect the hypocretin system, which is reduced in patients with narcolepsy, may become available and could be very useful, [although it is] likely to be many years,” he says.

Also, a new wakefulness-promoting drug is under development by Jazz Pharmaceuticals. Thorpy says, “JZP-110…is currently under investigation, and initial reports that have been published indicate that this has a beneficial affect on alertness. It looks as though this medication is going to be a very useful alternative to the wake-promoting medications that we have at the moment.”

In addition to gaining a better perspective on new treatment directions in narcolepsy, Thorpy hopes that attendees of the presentation found the information regarding the use of sodium oxybate to be the most helpful for their clinical practice. “I think one of the biggest changes has really been the use of sodium oxybate, which for some physicians is relatively new. Sodium oxybate is a medication that we didn’t have a lot of experience with a few years back, but over the years…we’ve come to understand and know how to use this medication and we’ve seen its effectiveness.”

The symposium was sponsored by Vox Media and supported by an independent educational grant from Jazz Pharmaceuticals.

Cassandra Perez is associate editor for Sleep Review. CONTACT cperez@allied360.com