Michael Thorpy on Treating Excessive Sleepiness

Michael J. Thorpy, MBChB, the director of the Sleep-Wake Disorders Center at Montefiore Medical Center

Michael J. Thorpy, MBChB

Michael J. Thorpy, MBChB, the director of the Sleep-Wake Disorders Center at Montefiore Medical Center, spoke with NeurologyLive about the difficulties of treating sleepiness in patients, and what those in primary care need to know about these conditions.

Treating the underlying cause of sleepiness, Thorpy said, presents multiple challenges for sleep specialists. While a shortage of physicians impacts the neurology community, more patients are being seen by primary care physicians and internal medicine specialists for neurological disorders, including sleep conditions. Thorpy noted that although the sleep specialist will always be necessary, there are instances in which a referral may not be required—though the challenges in treating these patients remain.

NeurologyLive: What are the challenges, or the needs that currently are not being met by other medications in these conditions?

MT: There a number of medications used for narcolepsy — the history of this originated with so-called traditional stimulants, things like methylphenidate and the amphetamine, and those are still used today, but they have significant adverse effects. People can develop tolerance to them, there can be mental stimulation—psychosis and irritability—and there can be cardiac consequences. So, they’re not ideal even though they help keep people awake. Then we went to a new type of drug, a dopamine agonist called modafinil, and a variation, a longer acting form called r-modafinil, and the advantage of these medications was little in the way of adverse effects, no cardiac stimulation, and they were not habit-forming or addictive, like the amphetamines, for example. So, they had a much better safety profile and they became the major drugs for the treatment of narcolepsy, shift work and sleepiness of OSA syndrome. However, there are still many patients who don’t respond, in fact, I was just reading about a case where one of these drugs, armodafinil, made the patient feel even sleepier.

They’re not perfect medications, and we need good, safe, effective medications. But treating sleepiness is very difficult, as there is always a drive for sleepiness that’s there, and what we are doing is helping people remain awake. Now, a lot of people don’t understand this about the alerting medications. These medications don’t get rid of sleepiness—they help people stay awake. So, if you have someone with narcolepsy, you can give them high doses of amphetamines, methylphenidate, or modafinil, put them in a darkened room, and turn the light out, and tell them to relax, they will go to sleep, even though they’re taking high doses of those medications. But if they’re doing something and want to be able to stay awake to be able to do it, they can stay awake more effectively with these medications. So, the medications do not get rid of the underlying drive for sleepiness that’s there the whole time, and that’s why many of these patients, when they take these drugs for sleepiness, still feel this background, unpleasant pressure for sleep, and often they will get headaches. They just don’t feel normal alertness, even though they’re able to stay awake longer. We definitely need better and more effective medications.

There’s another medication for narcolepsy called sodium oxybate (Xyrem), and this drug is interesting in that it has a totally different mode of action. It works on GABA_B receptors, not through a dopaminergic mechanism, and it helps patients stay awake during the daytime. Interestingly enough, with this medication, many patients say they don’t have that background feeling of sleepiness. They feel more normal. Not everyone, but many patients experience this effect. So, seems as though, in some way, sodium oxybate is actually getting rid of that underlying drive for sleep—that’s particularly interesting. There are some concerns with regards to sodium oxybate, though. It’s a sedative drug given at night, therefore you can’t give it with other sedative drugs, and there are some patients that have significant adverse effects. So Xyrem not ideal, but it is a very effective drug for narcolepsy. There is the potential to find a drug that gets rid of the background sleepiness and helps people remain awake so that they do feel more normal despite having severe sleepiness that needs treatment.

Are there any education concerns about sleep conditions, or the ability of medications such as solriamfetol to treat them, that you think maybe need to be addressed with primary care physicians or internists?

MT: As I said, sleepiness is not easy to treat because even though you can improve these patient’s ability to remain awake, there’s still this background feeling of sleepiness. Even in the best-treated narcolepsy patients, you find that surveys—and there are recent studies that have confirmed this—that most patients with narcolepsy, despite adequate medications, do not feel that they’re effectively treated, and they want new more effective medications. I think it’s fine for primary care physicians, if they understand sleep medicine, to prescribe solriamfetol. Certainly, it’s important that they have some education about the causes of sleepiness because the treatments can be so different. Obviously with sleep apnea, if you’re trying to treat a sleep apnea patient with a drug to improve their alertness, you are not addressing the underlying sleep apnea, and that’s a major error. And so, there needs to be education for primary care physicians to understand the differential diagnosis for excessive sleepiness, but once they’ve ruled out disorders like sleep apnea and conditions where they understand what’s causing the sleepiness, such as insufficient nocturnal sleep, then it’s fine for them to use these medications, and I think they will be used more widely. But there has to be an educational process, because if they not dealing with the underlying disorder causing the sleepiness that could be a problem.

If solriamfetol is FDA approved, then it is important people recognize the important diagnostic features of narcolepsy and sleep apnea. If people have excessive sleepiness that’s not caused by either of those two conditions, then the primary care physician needs to understand the differential diagnosis of sleepiness. Maybe it’s just because the person is just cutting themselves short of sleep, but there may be some other medical, or psychiatric, or neurological disorder that’s going on causing the sleepiness that needs to be determined. If a physician is comfortable with the diagnosis and it’s causing excessive sleepiness, then that’s fine, if the treatment of the sleepiness is the prime focus and directive. But in most cases, if the physician is uncertain what’s causing that sleepiness, he’s really got to refer to a sleep specialist to find why that patient has sleepiness. Take, for example, sleep apnea. It’s probably the most common cause of sleepiness the primary care physician sees. If that patient is treated effectively with CPAP or other upper airway treatments, but the primary care physician believes the patient still has excessive sleepiness and can be helped by a drug like solriamfetol, then it’s perfectly fine to go ahead and prescribe this as an adjunct medication to help improve their sleepiness. But the primary care physician has to know what he’s treating and has to know how the treatments are appropriate for that specific condition as well.

Any patient suspected of having narcolepsy should undergo evaluation by a sleep specialist because you do need to get objective documentation of narcolepsy. The insurance companies are demanding that before they approve treatment. And it’s the same for OSA syndrome. Anyone suspected of having sleep apnea has to have a sleep study to determine the severity of the sleep apnea and that needs to be treated directly. So, those two conditions do need referrals to a sleep specialist for evaluation. Subsequently, in most cases of narcolepsy, they are referred to a specialist anyway because narcolepsy can be very difficult to treat. There are a lot of components to narcolepsy we haven’t talked about aside from the excessive sleepiness. These patients can have catalepsy, terrifying nightmares, hallucinations, sleep paralysis, and disturbed nighttime sleep. So, there are other things that may need to be treated in a narcoleptic patient besides just the sleepiness. The physician needs to be aware of these other symptoms and take those into consideration when they’re managing the patient. Otherwise, they should refer them to a knowledgeable sleep specialist for ongoing management.

Transcript edited for clarity.