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For several years my colleagues and I have pursued a simple question with profound implications for psychiatric practice: how does psychotherapy work? We want to capitalize on major advances in our understanding of the neural basis of memory, emotion, and emotion-memory interactions. If we could start to explain the basic mechanism of action behind psychotherapy, then maybe we could understand how to conduct psychotherapy more effectively, with the ultimate goal of working with our patients to produce lasting changes in their mental health.

Recent studies have made important discoveries about the neural mechanisms underlying memory. Four are of particular interest. First, memories are not fixed entities; rather, they enter a labile state whenever they are reactivated, and can be modified or updated with new information during a 4 to 6 hour window after 

 Second, specific episodic (event) memories and semantic (generalizable knowledge) memories are highly inter-related in that they share neural mechanisms, and the latter are a distillation of the 

 Third, memories that are emotionally charged are remembered better than 

 And fourth, the activation of emotion appears to be a necessary ingredient of successful outcomes in 

Drawing upon these observations, my colleagues and I hypothesized that there were 3 key ingredients to lasting change in psychotherapy: 1) activating problematic memories and the associated painful affect; 2) concurrently engaging new emotional experiences that change old memories through reconsolidation; 3) reinforcing the strength of new memories and their semantic structures by practicing new ways of behaving and experiencing the world in a variety of contexts. In a 2015 article in a leading neuroscience 

 we briefly discussed the application of this model to 4 different psychotherapy modalities, including behavioral, cognitive behavioral (CBT), emotion focused (EFT), and psychodynamic psychotherapies..

Diving Into the Research—and the Clinical Implications

Realizing that there was much more to say about this new way of understanding change in psychotherapy, my colleagues and I published an edited volume, with multiple contributors, that both explains the basic science of memory and outlines a clinical application of our model. The new book, 

Neuroscience of Enduring Change: Implications for Psychotherapy

, expands upon the previous work in 3 sections.

 The basic science section includes chapters on emotion, memory, emotion-memory interactions, the role of language in shaping emotion and memory, and the role of sleep in memory consolidation and reconsolidation. The clinical section includes chapters from leading experts in psychodynamic psychotherapy, CBT, EFT, coherence therapy, and integrative approaches. Each author considers the role of memory reconsolidation in both psychotherapy and in achieving lasting personal change. The final section includes chapters on recurrent maladaptive patterns, a computational neuroscience perspective on the proposed model, and a discussion of a proposed preclinical and clinical research agenda.

Considerable effort was made within and across chapters to promote cross-fertilization between basic science and clinical application. Although it is written for neuroscience-oriented mental health clinicians, all psychotherapists, psychotherapy researchers, and scientists interested in memory, emotion, and their clinical application will find new ideas and practical advice in this book. An independent 

If one takes this model seriously it could influence psychiatric practice in several ways. For example, it is useful to consider how interventions might be adjusted in therapies that have stalled or have failed. Rather than talking about feelings with the goal of promoting insight, it is also important to experience feelings, especially the old painful feelings from which individuals have protected themselves for years, and to juxtapose these feelings with corrective emotional experiences.

Another clinical implication emerges from the observation that consolidation of emotional memories occurs primarily during REM sleep. Because reconsolidation may work in the same way, medications that inhibit REM sleep may be counterproductive to enduring change in psychotherapy. It is therefore important to know that selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitor, tricyclics, and benzodiazepines inhibit REM sleep, whereas trazodone, buproprion, and 

. The book describes these and other implications and provides a fresh perspective on how psychotherapy practice may be optimized and integrated in psychiatric care.

My interest in this topic emerged over the course of my 35-year career as an academic psychiatrist. I was initially trained as a clinical psychiatrist and psychodynamic psychotherapist and have continued to practice and supervise residents ever since. I was also fortunate enough to receive research training (resulting in a PhD in experimental psychology) that focused on cognitive neuroscience and functional neuroimaging of emotion. I have found the dialogue between the basic science of psychiatry and its clinical application to be particularly enriching and informative.

In my role as educator, I have become well acquainted with the challenges (eg, significant differences in the theoretical backgrounds, mindset, and clinical interventions required by these different approaches) psychiatry residents face in developing competence in CBT, psychodynamic psychotherapy, and supportive psychotherapy. Because there is a strong interest in finding common factors and common mechanisms across psychotherapy modalities, it occurred to me that a systems neuroscience perspective could provide an integrative mechanistic framework that would highlight commonalities instead of divergences. Moreover, the goal of integrating pharmacotherapy and psychotherapy is likely to be advanced by explaining how each works in brain-based terms. In my efforts to develop a new brain-based model of change in psychotherapy, I have been fortunate to have remarkable collaborators, including Lynn Nadel, PhD, Emeritus Professor of Psychology at the University of Arizona (a pioneer in the newly emerging understanding of memory).

It is important to emphasize that we have not yet established that change in psychotherapy occurs through memory reconsolidation. One of the conclusions of our book is that a focus of intervention is recurrent maladaptive patterns, which can be understood as an expression of schemas. Schematic memory is a type of semantic memory and, as an area of neuroscientific investigation, it is relatively new. It remains to be demonstrated empirically that schematic memories can be updated with emotional information. If so, it must then be determined whether this applies to psychotherapy. Although research of this type is still underway, it might be argued that it is important to consider the clinical implications of this model if it were true.

is professor of psychiatry, psychology, and neuroscience at the University of Arizona.

1. Phelps EA, Hofmann SG. Memory editing from science fiction to clinical practice. 

2. Ryan L, Hoscheidt S, Nadel L. Perspectives on episodic and semantic memory retrieval. In: Dere A, Easton J, Huston J, Nadel L, eds. 

3. Kalbe F, Schwabe L. Beyond arousal: Prediction error related to aversive events promotes episodic memory formation. 

4. Lane RD, Ryan L, Nadel L, Greenberg L. Memory reconsolidation, emotional arousal, and the process of change in psychotherapy: New insights from brain science. 

5. Auszra L, Greenberg LS, Herrmann I. Client emotional productivity-optimal client in-session emotional processing in experiential therapy. 

7. Kramer U. Review of “Neuroscience of Enduring Change: Implications for Psychotherapy.” 

8. Doghramji K, Jangro WC. Adverse effects of psychotropic medications on sleep. 

9. Borbély AA, Mattmann P, Loepfe M, Strauch I, Lehmann D. Effect of benzodiazepine hypnotics on all-night sleep EEG spectra. 

A brain-based perspective could explain how and why psychotherapy leads to enduring change. 

The Neural Mechanisms Behind Effective Psychotherapy

Let me ask you this as we’re closing. What do you think the role is in treating narcolepsy for psychiatrists and neurologists?

 If you’re part of the team, we have the opportunity to see these patients and screen and look for these questions. Then if you’re not comfortable with managing narcolepsy, find you a sleep doctor who is, but work with them because psychiatry and neurology needs to be involved. Psychiatrists really need to help. Once you have the diagnosis of narcolepsy, there’s some grieving about the 10 years that you didn’t know when you had all these failures. There are also some changes in the family. Suddenly these people with narcolepsy wake up and say, “Here I am,” and they want to change the routines and schedules for everybody, and that’s different. The dynamics are different. There are lots of reasons for psychiatrists to be involved, even if they don’t want to be the frontline person. But proper screening by the neurologists and psychiatrists would be a huge advancement for the disorder of narcolepsy. What do you think?

 Often you can stabilize this situation if you’re a sleep specialist. And the other role that can happen is psychiatrists should get enough comfort so that they continue the prescription. They may not want to initiate the prescription, and they may not want to decide among the options, but they should be able to move and accept referral back. Maybe they’re treating an underlying depression, as you said, or some other disorder, but they can facilitate the access to medicines by re-prescribing.

 Right, and diagnosing and treating the anxiety too. This has been a great discussion. It’s my pleasure to be working with you. I feel honored. I’m a superfan of yours. This has been great for me. I hope we’ve helped to educate some people about narcolepsy, and treatment options, and some of the behavioral things you have to consider with narcolepsy.

I would like to thank you all for watching this 

Dr Stephen Stahl is clinical professor of psychiatry and neuroscience at the University of California Riverside, adjunct professor of psychiatry at the University of California San Diego, and honorary fellow in psychiatry at the University of Cambridge. Over the past 12 months (January 2020 - December 2020), Dr Stahl has served as a consultant to Acadia, Alkermes, Allergan, AbbVie, Arbor Pharmaceuticals, Axovant, Axsome, Celgene, Concert, Clearview, EMD Serono, Eisai Pharmaceuticals, Ferring , Impel NeuroPharma, Intra-Cellular Therapies, Ironshore Pharmaceuticals, Janssen, Karuna, Lilly, Lundbeck, Merck, Otsuka, Pfizer, Relmada, Sage Therapeutics, Servier, Shire, Sunovion, Takeda, Taliaz, Teva, Tonix, Tris Pharma, and Viforpharma; he is a board member of Genomind; he has served on speakers bureaus for Acadia, Lundbeck, Otsuka, Perrigo, Servier, Sunovion, Takeda, Teva, and Vertex; and he has received research and/or grant support from Acadia, Avanir, Braeburn Pharmaceuticals, Eli Lilly, Intra-Cellular Therapies, Ironshore, ISSWSH, Neurocrine, Otsuka, Shire, Sunovion, and TMS NeuroHealth Centers.

Dr Debra Stultz is the Director and Owner of Stultz Sleep and Behavioral Health in Barboursville, West Virginia. Dr Stultz earned her medical degree from Marshall University School of Medicine in Huntington, West Virginia. She completed a residency in psychiatry and a fellowship in child and adolescent psychiatry through West Virginia University at their Charleston Division through Charleston Area Medical Center in Charleston, West Virginia. She is board certified in psychiatry, sleep medicine, and behavioral sleep medicine. With a special interest in Narcolepsy, she treats a variety of sleep disorders and psychiatric issues. She is also the editor for the Clinical TMS Society newsletter, on their Board of Directors, and the chairman of the TMS and Sleep Disorders Affinity Group. Dr Stultz is on the advisory committee for Harmony Biosciences and is a speaker for Harmony Biosciences and Jazz Pharmaceuticals.

In this custom video series, experts in sleep and neuroscience discuss the role of neurologists, psychiatrists, and sleep specialists in the treatment of narcolepsy and comorbid conditions.

Role of Neurologists and Psychiatrists in Narcolepsy Management

 Let’s move on and talk about pitolisant, or Wakix.

This is an interesting drug that has a unique mechanism of action, different from anything that has ever been used before. It is pro histamine. Usually I say it’s histaminergic, but every audience I’ve had since I started talking about this hears 

. No, it’s the opposite of an antihistamine. The so-called antihistamines are H1 postsynaptic antagonists, and you must know that histamine is a neurotransmitter in the brain. It doesn’t just make you itch. It’s an arousal neurotransmitter. It comes from an important part of the sleep-wake switch in your hypothalamus. These neurons go into the brain and arouse you and normally make you attentive and are even involved in cognition. You want to boost histamine in your brain, and you can do that by a couple of different mechanisms. Did you know that the presynaptic nerve has an auto receptor on it? It’s called an H3 receptor, and it’s there to be a brake and shut off histamine release. If you cut the brake cable, guess what? Histamine comes out, and the histamine comes out and wakes you up.

 It’s going to be dancing on those postsynaptic H1 receptors—histamine itself, but the drug releases histamine.

 This is an exciting medication. It’s been FDA approved for excessive daytime sleepiness and cataplexy. There have been some studies on it helping with sleep paralysis and hypnagogic hallucinations. The other main advantage of it is it’s not a controlled substance, so that’s a major advantage given a lot of the other medicines we have to deal with in narcolepsy.

 We’re late to the party. The United States got this, but overseas in Europe it’s been available for longer. My colleagues in Europe had much more experience with it than we did. They like it because it’s not overstimulating, it’s not a controlled substance, it’s not abusable, and it’s effective. It wakes you up and it has a refreshing effect, not like when you use too many stimulants; you’re way too much awake and people don’t like that. It’s almost better to not take the drug sometimes. This is not an adverse effect of pitolisant.

In this custom video series, experts discuss the uniqueness of pitolisant as a treatment option within the setting of narcolepsy and the role histamine plays in wakefulness.

Pitolisant and the Role of Histamine in Narcolepsy

 Let’s talk about some medicines that we’ve used for narcolepsy. Do you want to start with modafinil and armodafinil?

 Those are agents that would probably be best characterized as dopamine reuptake blockers. They’re mild stimulants. They’re weak stimulants in the sense that they probably don’t rapidly block the transporter and don’t completely block the transporter. Almost all the medicines are dedicated to boosting arousal. If you don’t have orexins to boost arousal, you have to have medicines to boost arousal. You remember the old reticular activating system—dopamine, norepinephrine, not so much serotonin, but histamine, acetylcholine. These are the more arousal neurotransmitters.

It turns out that you can be in trouble if you block any of the arousal neurotransmitters. That puts you to sleep. That’s the last thing you want to do. In treating people with modafinil, 1 of the first things you want to do is to say, “Am I blocking dopamine or any of these other neurotransmitters,” and stop those drugs if you can. But modafinil and its active enantiomer or armodafinil boost dopamine, but not norepinephrine transporters; it doesn’t look like it. In so doing, they have a mild stimulant effect and boost the arousal neurotransmitter dopamine. By doing that, they wake you up.

 Yes. These medications, I believe, have helped change the medicines when they came out—a new way to treat the success of daytime sleepiness. They do not have the same significant adverse effects on heart rate, blood pressure, and abuse potential that the stimulants have. One of the only things we had for several years for that was stimulants. They’ve been very beneficial medicines.

 The stimulants work sometimes too well because they work rapidly. They go up too high a dose; they overstimulate. It’s hard to adjust the dose. They often must be taken more than once a day, although there are some new ones that don’t. It’s hard to get a dose-response curve with stimulants that have the right amount of efficacy without the adverse effects. They tend to happen, but it’s much easier to do that with modafinil and armodafinil because they don’t have the overstimulating effects, and they don’t have the rapid onset and the big peaks. Sometimes you have to give them twice a day, sometimes just once a day. Because stimulants, unless you give the controlled release, must all be given more than once a day.

 Stimulants certainly have their place, and they add on, but they have more of an abuse potential and more cardiac effects. It’s interesting how you must dose them. Sometimes we have to add a sprinkle of it to some other medicines.

Let’s talk for just a minute about sodium oxybate. That medicine changed the face of narcolepsy for sure.

 It’s got a checkered history, but boy does it work to make narcolepsy better. It’s probably the most powerful drug to make you have slow-wave sleep.

 That’s a really good point. It helps with the disrupted nocturnal sleep. It’s FDA approved for excessive daytime sleepiness and cataplexy. There have also been some studies on it helping the sleep paralysis and hypnagogic hallucinations.

 The main problem is that it causes you to have to take it twice. It’s so short acting that it’s a pain to take sometimes. It’s a liquid. It’s also highly controlled. The access problems can be somewhat problematic or a hassle, but the good news is that it works so well that people are coming up with once-a-day formulations.

 Patients get used to it after a while. Now they have the new form with less sodium.

 It’s a heck of a sodium load, isn’t it?

 For people who have sodium, it can be a problem.

 But the new formulation has 92% less sodium and the same effectiveness, and it’s also been approved for sleepiness and cataplexy

 But most of what you want to do is make sure you’re stopping the medicines that cause the activation to be blocked, and you want to start medications that boost activating neurotransmitters.

 Right. We did leave 1, solriamfetol. We may talk about that, Sunosi. That’s interesting. I’m sure you will think from a neurotransmitter.

 It’s like a stimulant in a certain sense because stimulants are norepinephrine and dopamine reuptake inhibitors. Remember, I told you that bupropion is a norepinephrine reuptake inhibitor. Modafinil is a dopamine reuptake inhibitor. All these are good for different things on a theme, different variations of a theme. What’s interesting is that there are some good things that stimulants do without having the overstimulation.

 Right. One of the advantages of this medicine is it doesn’t have an effect on birth control pills, so that’s important for some young women. There can be effects on the birth control pill, like Provigil, or modafinil. One advantage of this medicine is it doesn’t have the effect on the birth control pill.

 Yes. That makes it attractive. It’s also been approved for the excessive daytime sleepiness of sleep apnea, as well as for the excessive daytime sleepiness of narcolepsy but not cataplexy. I haven’t seen any studies on its effect with the sleep paralysis or hypnagogic hallucinations.

In this custom video series, experts discuss the advantages and disadvantages of stimulating agents in the treatment of narcolepsy in addition to other notable pharmacological options.

Pharmacological Treatment Options for Narcolepsy

 We’re going to talk in a minute about what medications we would use, but there are also behavioral therapies we need to use with these patients. We need to talk to them about naps and how refreshing a 20-minute nap can be and keeping their sleep schedule regular. With the naps, 1 of the important things is to time their daily naps when they have their sleepiest period. If 2 o’clock is when they get really sleepy, then you plan the naps at 1 o’clock. Having a nap is necessary for patients with narcolepsy. In my mind, it’s the same as a person with who has to have frequent small snacks and has to keep something with them. The narcolepsy patient must plan on the naps and try to keep their sleep schedule regular.

 One of my old professors of biochemistry, who I worked with when I was in medical school, eventually was diagnosed with having narcolepsy because he was taking naps at work. But he was older, so maybe people thought he had it. He probably had a mild case his whole life, but what he would do is he’d have in his hand a big stack of keys that had a big metal name on it, and he was on this very hard floor that had a drain next to his chair, which was metal. He would take a nap as long as it took for him to lose the tone in his hand and drop the keys and wake up, and then he would go back to work.

 I don’t know [how long it was]—about 20 minutes—but he used that as his own alarm clock. That was a form of excessive daytime sleepiness. You’d find all sorts of odd stories like this if you actually look for them, and people find adaptive ways to try to deal with it and not get treatment.

 They’ve had to live with it forever. They go to their car at lunchtime and take a nap or know which restaurants have a place where they can safely take a little nap after they get.

In this custom video series, Debra Stultz, MD, leads a discussion on behavioral interventions for the treatment of narcolepsy and adaptation of patients in lieu of seeking treatment.

Behavioral Interventions and Adaptations in Narcolepsy

 There are different medical and psychiatric illnesses that can be confused during your work-up with narcolepsy. What do you think about that?

 The big 1, of course is OSA, obstructive sleep apnea. As you say, you can have it with narcolepsy, but you need to do that sleep EEG [electroencephalogram] to see if people are having apneic periods at night to make that diagnosis. That’s the big 1.

 Right. Or for any other sleep disorder, like restless leg or circadian rhythm.

 How about those acting out at night during sleep episodes, which you get with the onset of Parkinson disease. Or some hypnotic agents that make you act out weird stuff—you go down and eat from the refrigerator, come back to bed, and don’t know it.

 REM [rapid eye movement] behavior disorder. Other psychiatric disorders are also part of the differential if it’s depression, anxiety, bipolar depressed fatigue, anxiety, thyroid problems. There are a lot of things to consider. Medications that cause excessive sleepiness and timing. Are they taking their blood pressure medicine in the morning? Is it causing extreme sedation or substance abuse, or other substances?

 Absolutely. Antipsychotics are a big 1. A lot of people fall asleep with these agents that we give them in the daytime. They think, “Oh, I got narcolepsy because I’m falling asleep in the daytime all the time.”

 It could be just the medicines. But it’s common for people with narcolepsy to have psychiatric disorders, especially depression and social anxiety. But patients with narcolepsy are 16 times more likely to have anxiety. Just because they have those symptoms, it’s not 1 or the other. I had a provider say, “I’m going to treat the depression before I start working on the narcolepsy.” That, to me, doesn’t make sense. If you had a patient who had high blood pressure, diabetes, or COPD [chronic obstructive pulmonary disease] you would go in and treat their blood sugar, give them a medicine for their blood pressure and an inhaler. You would treat all 3. You wouldn’t say, I’ll just treat the diabetes, and we’ll see what happens with the rest. Having depression in narcolepsy, you’ve got to treat them both and treat them aggressively. The ongoing frustration with narcolepsy—having job problems, relationship problems, problems with your children—can lead to depression.

One other important point I’d like to make is sometimes people with severe cataplexy are trying hard to suppress their symptoms that they look flat and emotionless and seem depressed, but they’re not. I had a patient just like that, and I kept asking her about depression. I kept asking her, and she had significant cataplexy. She knew that if she got angry, or looked depressed, or suddenly got sad, then she was going to have this severe cataplexy. She was really blank and flat. And her kids knew that, so they knew they could get her frustrated and manipulate her. That was a really sad situation because you think of a mother trying to raise kids being completely flat.

 Yes. It may not be depression. It may just be they’re trying to suppress their symptoms. But there’s certainly coexisting depression just because you have the narcolepsy.

 Yes. If you think they have narcolepsy and they have depression, then 1 treatment alternative would be to use 1 of the antidepressants we’ve used to help cataplexy to treat the depression. We would use something like an SSRI [selective serotonin-reuptake inhibitors] or SNRI [serotonin-norepinephrine reuptake inhibitors] that could help with cataplexy and treat their depression.

In this custom video series, experts discuss medical and psychiatric illnesses that can be confused with narcolepsy as well as the presence and treatment of psychiatric comorbidities.

Psychiatric Comorbidities & Differential Diagnosis in Narcolepsy

 Well, there’s the rich man’s way and the poor man’s way. I’m not sure I can diagnose narcolepsy, but I can diagnose sleep onset and possibly even sleep-onset REM [rapid eye movement] in an airplane. This is my anecdote. If you get on an airplane, you’ll be on the runway and very quiet because you’re ready to take off. You can take 20 or 30 minutes in the quiet room. If you’re very observant, you’ll see this [his head falls forward]—all these heads breaking down and a lot of people going to sleep. They may or may not have excessive daytime sleepiness. I’m teasing. That’s very much how I diagnose narcolepsy. Put somebody in a room that’s dark and quiet and see how long it takes them to fall asleep. You can measure the latency to fall asleep. If it’s very quickly, then that’s not normal. There are a number of causes of excessive daytime sleepiness other than narcolepsy, but that diagnosis EDS, excessive daytime sleepiness.

 However, if you have an EEG [electroencephalogram] on at the same time, it’s not normal to go to sleep right into REM. That’s highly suspicious that you have narcolepsy. Some sleep deprivation can cause that as well; it’s not 100%. But sleep-onset REM, excessive daytime sleepiness, and latency to go to sleep very fast are all a diagnosis of narcolepsy.

 Right. To get the diagnosis, we do an overnight sleep study followed by MSLT, multiple sleep latency test, which is having the patient try to go to sleep 4 times every 2 hours, and we measure how quickly they go to sleep and what kind of sleep they have, and how quickly they get into REM sleep if they have REM sleep at all. We know we can use even an early REM sleep onset latency in their overnight setting, the PSG [polysomnography]. But by the strictest definition of narcolepsy, you must have 2 sleep-onset REM periods during the MSLT [multiple sleep latency test] or you could have 1 in the MSLT and 1 in the PSG.

 You don’t think these are often confirmatory? The way you get somebody to go through the hassle and expense of getting the test is different, which is to say that they fall asleep as a passenger in a car. Because if they have some of these problems, then they figure out to stop driving. If you’re at a traffic signal and that’s another way to say it, if you’re at a red light and you fall asleep, you’d better look into this a little. Does Grandpa fall asleep or does Mom fall asleep at the light? A lot of us do, but there are hints that people are sleeping too much, and they go rapidly into sleep. The other thing is they often wake up refreshed. It’s very funny how not all the time when I take a nap do I wake up refreshed, but that’s what these very brief episodes—you say, “Maybe we better investigate that,” then you do these fancy MSLTs and sleep EEGs.

 Those are good points about the history, about the naps being refreshing and how quickly they can fall asleep. The MSLTs can also be influenced once again if they’re on antidepressants or any REM-suppressant medications when they have the MSLT. It can make the MSLT negative. The other point I’d like to make is 1 MSLT does not exclude this diagnosis. Even having a negative MSLT at all does not exclude the diagnosis.

In this custom video series, Debra Stultz, MD, and Stephen Stahl, MD, PhD, share insights into diagnosing narcolepsy, including signs to monitor for, testing, and the potential for false negatives.

Testing and Criteria for Narcolepsy Diagnosis

There are other symptoms of narcolepsy, and that’s sleep paralysis and hypnagogic hallucinations. The problem with narcolepsy is REM [rapid eye movement] sleep. During REM sleep, your brain is very active. Your body is supposed to be paralyzed. All these symptoms occur with REM abnormalities. With sleep paralysis, the brain wakes up and the body is still paralyzed. Now, sleep paralysis can occur with anybody who has severe sleep deprivation. Doctors and residents have had it, shift workers have had it. There’s even a familial form of sleep paralysis, but narcolepsy patients get this 1 commonly, and it’s very frightening.

 Right. When they say they have panic attacks at nighttime, I’ll start thinking could it be sleep paralysis because they wake up, and their heart is racing. They can’t move. One of my patients had a particularly good description of this. He called it sleep drowning. He said, “Have you ever been right under the water, and you’re trying to get up but you can’t?” That’s exactly what it’s like. I thought that was a great description.

 Hypnagogic hallucinations are abnormal sensations: hearing voices, seeing things, sensing a presence when you’re going to or coming from sleep. It’s usually going to sleep. These symptoms, although not necessary for the diagnosis of narcolepsy present, can be quite disturbing. Patients are very frustrated when they have these symptoms, and they don’t necessarily link it with the sleepiness or even the cataplexy. Sometimes they’re very surprised when I ask them about it. They’ll go, “How did you know that?”

 Maybe it’s something that’s frightening, and they don’t want to go to sleep then.

 Right, it can contribute. It’s a vicious cycle. That brings up the next point: insomnia, or disrupted nocturnal sleep. There have been reports of a doctor saying you can’t have narcolepsy if you have insomnia. I had a patient tell me that once, but that’s just not true. The same way the light flickers during the day with REM phenomenon, wake flickers into sleep. People who have narcolepsy have decreased sleep efficiency. They may go to sleep quickly, but they don’t stay asleep. They have more stage I sleep. They have more transitions in sleep. They have early onset REM periods. Obviously, we need that for the diagnosis. Even though they’re asleep, they’re not sleeping right, and they’re not sleeping deep. Their sleep is very fragmented.

 They’ve got to have a rhythm. You’ve got to be awake, and then you have to be asleep. Then during sleep you have rhythms within sleep. Once you start losing that, I would say all hell breaks loose.

 Right. The thing about narcolepsy is that this is usually developed over a number of years, with the sleep problem starting first. Maybe the cataplexy doesn’t present for several years. Some people are used to it. They’re used to not sleeping well, and they focus on just the hypersomnia. You’ve got to tease out these symptoms.

In this custom video series, experts within the fields of sleep and neuroscience discuss additional symptoms that can occur in patients with narcolepsy and REM cycle abnormalities.

Symptoms of Narcolepsy: Sleep Paralysis & Hallucinations

We have several other symptoms, but one of the other specific symptoms for narcolepsy is cataplexy. When I was in medical school, and they taught us about narcolepsy—at that time you had to have all the symptoms to get the diagnosis—they showed a video of a man who had narcolepsy. He was standing with his wife, and she would talk about something. He would get emotional, and he would fall to the floor. There was another video of him sitting in the chair, and he would fall to the floor. OK, I got that. When I see that, that’s cataplexy. But cataplexy is much more than that. It can be a vague symptom. It can be any muscle in your body.

When I’m describing it to patients and I’m talking about the symptoms, I’ll start at the top of the head, with drooping eyelids or even blurred vision. I’ve had a couple of ophthalmologists send me narcolepsy patients, and I’m so excited about that. Their jaw droops. The jaw weakness is especially common in pediatric cases. The patient with pediatric narcolepsy will have a loosening of the jaw, and their tongue will protrude a little.

After you’ve seen it for a while, you recognize that it happens with their jaw and have neck weakness, like people bobbing with their head. You can have shoulder weakness, arm weakness, hand weakness. I had 1 patient with narcolepsy who said she would be working on something stressful at work, and she just drops her pen. The most common cataplexy is the knees buckling and that weakness that even your calves can get weak. Patients have told me, “I can’t wear high heels anymore because I might fall.” It can be any muscle, and it can occur with most any emotion. Laughter is the most common, but it can occur with anger, frustration, even sexual excitation. Any strong emotion that precipitates a muscle weakness is what cataplexy is.

 Very fascinating. You made some really important points. You have the idea that cataplexy doesn’t have to be these dramatic things. Most of us have seen these videos in our training.

 Maybe you’ve even seen the Doberman dogs that are bred for cataplexy, and they run across and they collapse, and they get up and they run and collapse again. That’s interesting, but it’s not helpful because you will miss the more subtle forms. That’s a nice set of descriptions that you had there. I don’t see a lot of cataplexy in my own practice, although I did have a case I wrote up a million years ago, last century when I was a neurology resident at UCSF [University of California, San Francisco School of Medicine] and we had a brain stem tumor. That person had disruption of the sleep pathways that caused him to collapse. My neurology attending [physician] was very clever. He collapsed, and everybody thought it was a cardiac event. He was a younger guy, so it wasn’t all that credible. We were working him up for the possibility of a brain stem tumor. On the floor, the guy was completely limp. He opened up his eyes and said, “Move your eyes left and right.” That’s 1 of the ways to tell it wasn’t a heart attack and he was awake, but he couldn’t move them. His eye movements were preserved but had atonia.

 Right. When people do see the cataplexy, they may be confused that the patient is still aware. They’re aware what’s going on, but they can’t speak. Their eyes may move, and that’s why cataplexy is often thought of a psychiatric disorder. A lot of times when patients have cataplexy, they can sense it is coming on. Almost like when people are about to faint, sometimes they’ll hold their arms out before they faint. Other times people just hit the floor from fainting. The cataplexy is the same way. They can feel it coming on, so they don’t fall as often into something. Then it will be like it must be psychiatric because when they fell they didn’t get hurt. But I don’t think that’s true either. You have to tease it out.

 Yes. What you really have is a normal state in the wrong phase of wakefulness.

 We normally go into that state when we dream, so we don’t act. Some people think it’s because you don’t act out your dreams when you’re paralyzed. The reality is that it’s miswired. Somehow, you’re connecting this “atonia”—lack of tone—at the wrong time when you’re awake and you need your tone.

 Right. Let me make 2 more points about cataplexy before we move on. If you’re seeing a patient, especially if you’re a psychiatrist seeing a patient or anybody seeing a new patient, if they’ve been on antidepressants for a long time, they may have suppressed the cataplexy. You might have to ask them about what happened before. Patients are often not the best historians for this symptom. They go home and talk to their family: “Yeah, that thing you do when you’re laughing.” It’s like, “What thing that I do when I’m laughing?” That’s a symptom you’ve got to keep asking about.

In this custom video series, Debra Stultz, MD, discusses cataplexy, a vague symptom precipitated by strong emotion that can be masked by certain medications.

Symptoms of Narcolepsy: Cataplexy

 Let’s talk for a minute about the symptoms of narcolepsy. Everybody is most familiar with excessive daytime sleepiness. In fact, that’s the only symptom that you need to have the diagnosis of narcolepsy. These other symptoms go along with it and help you make the diagnosis, but you have to have only excessive daytime sleepiness. The problem is people use a lot of different words to describe excessive daytime sleepiness. “I’m really tired. I can’t function. It’s like I’m attached to the couch. I can’t get up in the morning.” They have all these symptoms for fatigue. It causes a great deal of irritability, but their descriptions are sometimes so vague that people don’t know what to do with it. It’s a very important symptom to listen to.

They present to primary care offices, psychiatrists, and neurologists with complaints of, “I can’t stay awake. I fall asleep unintentionally. I get sleepy when I’m driving.” That’s 1 question you can ask them: Have you had accidents? “I have to stay busy all the time, or I’m going to go to sleep.” That description gets psychiatrists thinking: Are they anxious? Are they bipolar? Are they staying busy all the time? That’s the way they’re trying to fight the sleepiness.

 Sleep is like a vital sign in psychiatry. It goes off with lots of disorders, so you can be confused. Is this an anxiety disorder? Is this a mood disorder. A psychotic disorder? Because sleep is abnormal in those disorders. You say excessive daytime sleepiness. You can be excessively sleepy in the daytime from not sleeping at night, from burning the candle. It’s a common 1, but it’s not a pathological 1. It may be a lifestyle 1. But the big 1 is obstructive sleep apnea. If you’re not sleeping at night, you can have daytime sleepiness and not have narcolepsy. You have a different cause of it.

 People are tuned in to question for sleep apnea. Sometimes that’s as far as it goes, even in the sleep labs. And the thing of it is, sleep disorders are similar to psychiatric disorders. They run hand in hand: If you have 1 sleep disorder, you’re more likely to have another. Studies have shown about 6% of people with sleep apnea, and in some studies up to 30% of people with sleep apnea can have narcolepsy. Of those patients with narcolepsy, about 25% can have obstructive sleep apnea. I hope what we can do is to get people thinking of both disorders because sleep apnea and snoring are clues that people need to do a sleep study. But if they are sleepy, we need to keep looking.

 Right. It’s not normal to want to sleep all the time.

Other things people look for: Are you sick? Do you have cancer? Do you have fatigue from mental disorder? You must rule all those out because they certainly can be making that fatigue, but they really don’t make you “asleep” so much.

 Yes, they make you feel tired, but you don’t sleep. That’s a good point.

In this custom video series, experts within the fields of sleep and neuroscience discuss sleep as a vital sign and causes, in addition to narcolepsy, for excessive daytime sleepiness.

Sleep Disorders