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Dr. Moawad, let's just turn to you for your overall impressions of this case and what stands out to you.

 Actually, this patient's history is, in many ways, so typical because he is attempting to explain his symptoms with the things that are going on in his life. He is not doing well in school. He is flunking his classes. And so he is describing the depression, the sleepiness, all of these things based on the events that are going on for him. Especially at this age, this is a normal way that a young person would describe what is going on with them. One thing that I do think that stands out is that he has been taking medication for a while and that can really have a lot of side effects and can change things that he doesn't seem to have been maybe warned about, what side effects to look for. I think that is coloring what's going on here. But the other thing that is really standing out is how persistent all of this is. A lot of times, when young people in particular try to explain symptoms with what is going on in their life, it shouldn't be so prolonged. In this case, we're talking about a 19-year-old, and he has been dealing with this since he was 16. It is definitely something to look at deeper.

He is problematically sleeping. How would you tease apart this question of depression and narcolepsy in this guy?

 Well, I think I actually do think that the scales would be helpful in this type of situation. One thing is that it opens up the discussion. It helps him to consider sleepiness in isolation from mood and to consider how much he's been sleeping, how much he falls asleep. Also, it allows for a discussion about the fact that this is not necessarily normal and that he really needs to start tracking this a little bit more. I think it is just an opening for sleep studies, which would be more definitive for him.

It sounds like just with this kind of history, after taking a good history, you would certainly move on to doing an overnight polysomnogram and multiple sleep latency test.

 Yeah. Given how long he has been dealing with this and that it seems that the conditions in his life that he is blaming all of this on are not getting—as probably things are fluctuating during summer vacation and things like that—it doesn't seem like his symptoms are getting better during those times.

: One thing that I notice is that we have this strong focus on excessive daytime sleepiness, daytime functioning, and there have been no questions about his nighttime sleep, being a college student, how regular sleep is. I think Dr. Benca brought up the issue of sleep deprivation being very common in this group. I think that's probably something I would be really interested in knowing about his sleep quality, the regularity as well, because that is important not to miss that in the history.

I think you're highlighting the fact that way more common than narcolepsy is insufficient sleep, circadian phase delay, things like this are really what it's most typically causing these kinds of problems in this stage group. Dr. Benca, were you going to say something?

 Yeah. Certainly, all of that is true, but it is also an age group where narcolepsy sometimes appears. We do have to keep that in mind, but I agree with Dr. Zee that particularly in young people like this, we do need to get a very careful sleep history. Does he have early morning classes and is staying up really late at night? Does he have an irregular pattern social jet lag, whatever that is contributing to his sleepiness? The other concern I have about him is his substance abuse history. Again, is he self-medicating because he is sleepy, or is he sleepy because he's addiction-prone in using stimulants that have their side effects when you withdraw excessive sleepiness, like the cocaine? And although he says he has not been using for a month or two, that's not really indicative of recovery from substance abuse, and he is smoking a pack a day. That also raises concerns about how we're going to treat him because he's clearly someone who does tend to abuse substances.

Yeah. I think it's obvious, but do you want to comment on the caffeine and the nicotine and his sleep patterns?

 I just have one other thing to add, which is that a young person at this age who's having trouble in school could potentially have undiagnosed ADHD or learning disorder and that can be contributing to his drug use as a way of coping with these difficulties.

Heidi Moawad, MD; Phyllis C. Zee, MD, PhD; and Ruth Benca, MD, PhD, share details about a patient case that may impact clinical considerations and therapeutic decision-making.

Clinical Impressions from Patient Case #1

Let’s transition to talking about an actual clinical case, so that we can put some of these thoughts in context. This is a 19-year-old man who presented to his psychiatrist with excessive daytime sleepiness. He has been seeing his primary care physician for the last 3 years for his condition. He says that he was diagnosed with depression at age 16 when he was in high school. For that, he is taking fluoxetine 20 mg each morning. He took it as prescribed, but he now takes it every other day because he feels that his depression has improved. He still has some days when he feels depressed, but he says that is mainly because he is failing his classes and he has been put on academic probation; he does not really see it as an intrinsic problem. He has been self-medicating for the last 3 months with caffeine and energy drinks and over the counter agents to try to improve his sleepiness, but he does not find them effective. There is no history of trauma or head injury. The past history is notable for the depression, and he does have a prior history of marijuana and cocaine abuse, but he has not been using it for the past couple of months. He is currently a full-time college student. He does smoke one pack of cigarettes a day, and, as I mentioned, he is on academic probation because he is not doing well academically, which he says is because he cannot stay awake and study properly. The only medication right now is fluoxetine 20 mg and his labs are all fine.

Thomas E. Scammell, MD, presents a case study for a college student with a history of sleepiness.

Patient Case #1: 19-Year-Old Man With Excessive Daytime Sleepiness

 Around the Practice program on the management of narcolepsy. I am Tom Scammell. I am a Professor of Neurology at Harvard Medical School Beth Israel Deaconess in Boston Children’s Hospital. I am joined by Dr Heidi Mowad, who is a clinical assistant professor of neurology at Case Western Reserve University School of Medicine in Cleveland, Dr Ruth Benca, who is a professor and chair of psychiatry at Wake Forest School of Medicine and Dr Phyllis Zee, who is a professor of neurology and director of the circadian and sleep program at Northwestern University School of Medicine. In addition to reviewing the diagnosis and management of narcolepsy, we will be presenting 2 hypothetical patient cases and will be talking through approaches to treatment. Let’s begin.

Let’s just start off generally talking about the challenges of diagnosing narcolepsy. How often is it underdiagnosed, or misdiagnosed? Why has it proven so difficult to properly diagnosis, and what is the differential diagnosis? Dr. Zee, do you want to start us off with that one?

 When you look at the data that has been published about the lag between presentation of symptoms of narcolepsy to diagnosis, it can lag up to about 3 to 8 years. Some of it is because it is misdiagnosed or underdiagnosed about 60% of the time, and that is a huge number. Of course, in addition to lack of awareness, or perhaps lack of familiarity with the disorder, probably what is driving this are common comorbidities that exist in patients with narcolepsy, such as depression and anxiety disorders. There are also other sleep disorders like sleep apnea, which is actually common in patients with narcolepsy, and even circadian rhythm sleep disorders. Excessive daytime sleepiness is so common; it is very nonspecific to many of the conditions that psychiatrists and neurologists take care of. Also, many patients are on medications that could mask some of the symptoms of narcolepsy. I think those are some of the common reasons for some of the missed or delayed diagnoses.

You mentioned that depression is often comorbid with narcolepsy. Dr. Benca, do you want to talk about how these symptoms can get blurred together?

One thing that a significant subset of patients with depression will complain about is excessive daytime sleepiness. Some of them are actually excessively sleepy and some of them are just really fatigued and don’t show objective evidence of excessive sleepiness, but they will report that they are sleepy. The other issue is that, like narcolepsy, mood disorders are sometimes characterized by early entrance into REM sleep. You can sometimes see shorter REM latency in patients with mood disorders, so there can be some overlap there.

In addition to narcolepsy often not being diagnosed in a timely manner, conditions often get diagnosed as narcolepsy inappropriately. One of the things I’ve seen more is people who are simply sleep deprived, such as those who are doing shift work, or physicians, who may be doing a lot of call and are not getting enough sleep and are falling asleep at work. These folks often get diagnosed with narcolepsy. Actually, they are just sleep deprived.

What kind of tools do you use to actually evaluate daytime sleepiness and separate it from, for instance, a more typical sense of fatigue and depression?

One thing is that you do a more careful clinical exam. One of the issues I see a lot in psychiatry is that patients report that they are tired. We assume they are sleepy. I always try to distinguish if they are tired and falling asleep inappropriately, or you just wish you were asleep and you’re exhausted.

Diagnosing narcolepsy, we generally do sleep testing. That is where it is really important to verify that patients are not sleep deprived and are sleeping adequately, and that they get sufficient sleep before we do their multiple sleep latency test.

Do you like the Epworth Sleepiness Scale?

The Epworth Sleepiness Scale just tells you whether the patient thinks they are excessively sleepy. It is not specific to any particular sleep disorder. Sometimes patients who are simply fatigued may report very high Epworth scores. I see that a lot in psychiatric patients. They sometimes have high Epworth scores but when we test them objectively, they are not actually sleepy.

One question I like to ask under those circumstances is: How many times do you actually fall asleep when you did not plan to in the last week? Because I agree with you. Sometimes there is a little inflation on the Epworth sleep score. People say, “I could fall asleep when I am watching TV.” Then I ask, “Did it really happen?” Usually the answer is no. Getting down to the nuts and bolts of falling asleep could be useful.

 One of the things I try to do is to see whether there is any cataplexy. It is quite amazing to me how oftentimes we miss that because we are asking about big things. Are you falling when you laugh hard? Do your knees buckle? Even if they say “No” to that, I try to probe deeper to see if I can get some of the milder symptoms, perhaps mild manifestations of cataplexy. Often times that can be helpful, especially to diagnose narcolepsy type 2. That can be more specific.

There is another screening tool if you are trying to determine whether someone has type 1 narcolepsy, and that is the Swiss narcolepsy scale. It is a 5-item scale that does elicit symptoms of cataplexy. It is a little bit more complicated to score, because you have to go through a formula. It doesn’t really help you with those patients who might have type 2 narcolepsy or narcolepsy without cataplexy, which are the group that tends to overlap a lot with other disorders that might present with hypersomnia, including mood disorders or even idiopathic hypersomnia.

A multidisciplinary panel of experts outline the difficulties of distinguishing narcolepsy frfom other sleep disorders and psychiatric comorbid conditions.

Challenges in the Diagnosis of Narcolepsy

In this installment of the Around the Practice custom video program, Heidi Moawad, MD; Ruth Benca, MD, PhD; and Phyllis C. Zee, MD, PhD, reviewed the diagnosis and management of narcolepsy, joined by moderator Tom Scammell, MD. Leveraging 2 hypothetical patient cases, the panelists walked through potential approaches to treatment.

Narcolepsy is either misdiagnosed or underdiagnosed about 60% of the time, with initial diagnosis lagging anywhere from 3 to 8 years, said Zee, director of the Center for Circadian and Sleep Medicine and chief of the Division of Sleep Medicine, Department of Neurology, at Northwestern University Feinberg School of Medicine. She added that depression is often comorbid with narcolepsy and symptoms can blur, making a diagnosis challenging.

“A significant subset of patients with depression will complain of excessive daytime sleepiness. Some of them are actually excessively sleepy and some of them are just really fatigued and do not show objective evidence of excessive sleepiness, but they will report that they are sleepy,” said Benca, professor and chair of the Department of Psychiatry and Behavioral Medicine at Wake Forest University School of Medicine. “The other issue is that, like narcolepsy, mood disorders are sometimes characterized by early entrance into REM sleep. You can sometimes see shorter REM latency in patients with mood disorders.”

The panelists discussed tools to help assess and properly diagnose sleep issues. The self-administered Epworth Sleepiness Scale includes 8 questions in which patients are asked to rate how often they doze or fall asleep while engaging in certain activities. Similarly, the Swiss Narcolepsy Scale aims to identify certain behavioral symptoms associated with narcolepsy with cataplexy. Both scales, however, are subjective in nature, so the panelists agreed it is important to probe further.

As part of her intake, Zee looks at lifestyle and behavioral issues that may impact sleep, like diet, exercise, and substance use. She often reviews a sleep and diet diary, suggesting to patients that smaller meals can be helpful. Light therapy and even cognitive behavioral therapy can be helpful for these patients, she added. Benca agreed, noting that for some patients, avoiding carbohydrates but having other kinds of healthy snacks can be useful. She tells patients to get up and move around when they feel sleepy, too. Scammell reiterated that it is very important to educate patients about nonpharmacological factors that can prove beneficial and that can lead to a healthier life in general.

As a general rule, Moawad said she often turns to traditional agents that she finds to be effective treatment options, including modafinil and armodafinil, amphetamines, and sodium oxybate. “They’ve been around for a long time,” she explained. “When patients use them as directed, they’ll notice improvement.” However, the panelists also discussed some of these agents’ associated adverse events. First, there may be risk of abuse with these medications. Benca pointed to the psychiatric adverse effects associated with sodium oxybate, and noted it can result in psychosis, triggering of bipolar episodes, and worsening depression. Similarly, there may be risk of abuse for these medications. Finally, there are cardiovascular concerns. Scammel noted research has shown an increased risk in these patients to begin with, so adding something like amphetamines may increase the concern. In recent years, the US Food and Drug Administration has approved novel agents like pitolisant, solriamfetol, and lower-sodium oxybate, which the panel agreed may offer similar efficacy with less risk of abuse and fewer cardiovascular effects.

A male college student, aged 19 years, presents for evaluation with excessive daytime sleepiness. He has been seeing his primary care provider for the last 3 years for this condition, and he was diagnosed with depression when aged around 16 years. He was prescribed 20 mg of fluoxetine daily in the morning, but now he takes it every other day because he feels his depression is much improved. On some days he feels moderately depressed, but he is mainly worried about failing his classes, as he has been put on academic probation. He has been self-medicating for the last 3 months with caffeine, energy drinks, and over-the-counter products in hopes of improving his sleepiness, but he does not find them effective. He has no history of trauma or head injury, but he does have a prior history of marijuana and cocaine abuse, although he has not been using either for the last couple of months. He smokes 1 pack of cigarettes a day. He blames his academic struggles on his inability to stay awake and properly study.

Moawad, a clinical assistant professor in the Division of Medical Education at Case Western Reserve University School of Medicine, noted that this patient’s history is typical in many ways because he is attempting to explain his symptoms with things that are going on in his life, like failing classes. To her, the persistence of the symptoms was a red flag. “[The sleepiness] should not be so prolonged in this case,” Moawad noted. “We are talking about a 19-year-old, and he has been dealing with this since he was 16. It is definitely something to look at more deeply.”

An overnight polysomnogram or multiple sleep latency test might open up the discussion about sleepiness with the patient, the panel suggested. Sleep history—particularly in the patient’s age group—is important, stressed the panel. Having the patient consider sleepiness as a separate entity from mood might help him better track his symptoms.

“Working with psychiatrists to help manage the comorbid psychiatric illnesses and providing emotional support to these patients may be useful,” said Benca.

A 27-year-old woman who was previously diagnosed with depression and daytime sleepiness presents to her psychiatrist because she is having episodes of whole-body weakness, which resulted in a fall. She has been treated with paroxetine since she was aged about 24 years, and she has also been taking amphetamines/dextroamphetamine (extended-release Dexedrine Spansule, 30 mg/day) for about 2 years for her sleepiness. In the last couple of months, she says her moods improved and the paroxetine was stopped 3 weeks prior. Since then, she has had 3 episodes of weakness, each lasting about 30 to 60 seconds. With the first episodes, her head fell forward and her speech was slurred. When the third episode occurred, she was joking with a friend and became so weak that she had to slump into a chair and could not stand for a minute. She found these incidents extremely bizarre and frightening.

The patient, who is married and has several children, is unhappy with the amphetamine/dextroamphetamine, because she thinks it is causing decreased appetite/weight loss, headache, increased heart rate, and irritability. She is currently on alprazolam (Xanax) and buspirone (Buspar) for her depression. She does not take illicit drugs or drink alcohol.

“This sounds awfully suspicious for narcolepsy with cataplexy. Not only do the episodes sound like cataplexy, but also that spells were exacerbated with the discontinuation of the drugs,” noted Benca. “On the other hand, I have had psychiatric patients come in and complain to me of weakness or falling episodes that are not cataplexy.” She added that it is important to be cautious in understanding the triggers, especially in patients with psychiatric disorders, to make sure they really fit classic cataplectic diagnosis.

“This case in particular really highlights the idea that the disease can change, that the symptoms can change. It is always important to reassess the symptoms,” added Moawad.

Zee recommended switching to another selective serotonin reuptake inhibitor that could address both the cataplexy and the anxiety and depression symptoms. Benca added that specifically, another potential option was sertraline, if looking to minimize adverse effects. Additionally, the panel agreed that the patient should be tapered off of amphetamine, while her symptoms were monitored.

Comorbid psychiatric issues are quite common in individuals with narcolepsy, the panel concluded.“A lot of our patients complain about sleepiness and tiredness. Some of them are going to have narcolepsy—very few, but it is kind of like finding the needle in the haystack,” Benca said. “It is so critical to make the right diagnosis.”

To watch this and other Around the Practice progams visit 

https://www.psychiatrictimes.com/around-the-practice

is a clinical assistant professor of neurology in the Division of Medical Education at Case Western Reserve University School of Medicine in Cleveland.

is professor and chair of the Department of Psychiatry and Behavioral Medicine at Wake Forest University School of Medicine in Winston-Salem, North Carolina. 

is the Benjamin and Virginia T. Boshes Professor of Neurology, director of the Center for Circadian and Sleep Medicine, and chief of the Division of Sleep Medicine at the Northwestern University Feinberg School of Medicine in Chicago. Faculty disclosures are available online.

In this installment of the Around the Practice custom video program, doctors discussed management of narcolepsy. 

Narcolepsy: Making the Right Diagnosis

Teralyn Sell, PhD, MS, NCC, LPC, shares 5 foods that can help improve your patients' sleep. They are:

holds a doctorate in psychology and is the founder of Pro Recovery Rx, a supplement line dedicated to supporting brain health for individuals in addiction recovery. She also teaches a class called NeuroHealth Coach, which helps professionals integrate brain health into their daily lives.

These 5 foods can help improve quantity and quality of sleep. 

5 Foods to Improve Sleep

. Many patients with psychiatric disorders will tell us that sleep needs to be addressed,” said Colin A. Espie, PhD, Professor of Sleep Medicine in the Nuffield Department of Clinical Neurosciences at University of Oxford, Clinical Director of the Oxford Online Programme in Sleep Medicine, and Cofounder and Chief Scientist of Big Health.

 Associate Editorial Director, Heidi Anne Duerr, MPH, teamed up with Espie to discuss sleep issues and mental health in the session, “How Big Health Are Tackling Wider Mental Health Issues by Addressing Sleep.” Together, they looked at the prevalence of mental health and insomnia across multiple populations.

“Research has shown that it really is important to address both sleep and psychiatric disorders. If sleep is not addressed in patients with depression or 

, then it could very well exacerbate their psychiatric condition and vice versa,” Duerr shared.

Psychopharmacological options are very important to treat sleep disorders, the pair discussed, but so is 

 (CBT) that is associated with addressing sleep issues.

“CBT is not a treatment, but a family of treatments,” said Espie. “It contains bits that deal with the racing mind, the cognitive element of CBT, and addresses our approach to sleep.”

“In the headlines and in the news, we hear that there are shortages of mental health care professionals who can treat patients, including offering CBT to help patients,” continued Duerr.

The potential solution to such shortages? 

 (DTx) may be poised to step in, so long as they are utilized by empathetic doctors who are ready to be there for their patients. According to Espie, mental health treatment must be given the same respect and be held accountable as any other health care, and DTx are no exception.

“We must give them [our patients] treatments that work,” said Espie. He believes DTx must (1) work correctly, and (2) be provided only after they are validated via randomized, placebo controlled trials.

“Digital therapeutics need to be skillfully made, they cannot just be translations,” said Espie. “We need evidence-based treatments that are sophisticated enough to really help people to implement things in their life that make a difference.”

Something investigators should be aware of, Espie noted, is potential placebo effects of DTx. Just as with regular medications, DTx will not be regarded as effective treatments unless they produce benefit beyond placebo.

From the discussion, it is clear that DTx have the potential to improve patient care—and increase the number of patients receiving care. With more evidence-based research, the availability is likely to increase in the near future.

Digital therapeutics may be poised to step up as the next CBT. 

Need Your Sleep: DTx for Treating Comorbid Insomnia and Psychiatric Disorders

The average patient with bipolar disorder (BD) spends half their life struggling with mood symptoms and the other half struggling with sleep.

 Insomnia persists in 70% of patients even when their mood is stable, and these sleep problems put them at risk for more episodes of mania and depression (

 Some clinicians are liberal with hypnotics, while others prefer the lower abuse potential of sedating antidepressants like trazodone. Both these approaches have problems. Fortunately, there are also new therapies that improve mood and sleep by entraining the circadian rhythm (

 or z-hypnotic (eg, eszopiclone, zaleplon, zolpidem) could halt the progression of insomnia into mania, but the idea has never been adequately tested. These GABAergic hypnotics lack controlled trials in BD, and the few observational studies paint a mixed picture. A chart review of 278 z-hypnotic trials in adolescents with BD concluded that the drugs improved 

 in 40% to 60% of patients and did not lead to abuse with long-term use.

 On the other hand, reports document 30 cases of high doses of zolpidem and regular doses of alprazolam and triazolam inducing mania.

In contrast, clonazepam and lorazepam appear safer, with small controlled trials suggesting that these agents do not worsen, and may improve, manic symptoms (the 

 were not used as hypnotics in these trials).

 However, over the long term, benzodiazepines carry risks of tolerance and dependence, and long-term use may worsen cognition and mood in BD, according to nonrandomized studies that attempted to control for the confounding tendency to prescribe benzodiazepines in more severe cases.

 in BD is to choose mood stabilizers with sedative effects. Many antipsychotics are sedating, but some have more meaningful benefits in sleep quality; these include quetiapine in particular, and possibly lumateperone, olanzapine, 

Lithium is rarely sedating, but it does have positive effects on the circadian system, such as dampening the phase-advance (“night owl”) tendency that is associated with poorer health and greater risk of depression.

Sedating antidepressants are more problematic, particularly in bipolar I disorder, in which the risk of manic induction is high. Most, including trazodone and 

, are associated with case reports of triggering mania. In a retrospective study, patients with BD who used sedating antidepressants for sleep were significantly more likely to develop mania and episode acceleration than those who took traditional hypnotics.

Melatonin agonists have captured the interest of investigators because of their potential to realign the circadian system, which is often disrupted in BD. Pure melatonin failed to improve sleep, 

, or rapid cycling in 2 small controlled trials,

 but the melatonin agonist ramelteon has intriguing results from 3 industry-sponsored, randomized, placebo-controlled trials in BD. Although ramelteon failed to improve sleep or mania, it did prevent depression in patients who struggled with insomnia.

The first study tested ramelteon in 21 patients with acute mania and found a reduction in depressive symptoms but no benefit in mania or sleep.

 Next, ramelteon was tested in 83 patients with BD who had active 

 but stable mood. For 6 months, they took either placebo or a nightly dose of ramelteon 8 mg. As in the first trial, ramelteon did little to improve sleep (there was only a nonsignificant trend), but it did lower the risk of depression, more than doubling the time to a new episode from 84 to 188 days (P = .02).

 A larger study attempted to replicate that finding, but the results were negative across all outcomes.

One explanation for these intriguing results is that the positive trials enrolled patients with active insomnia, while the negative trial did not, suggesting that ramelteon might have preferential effects in patients with disturbed circadian rhythms. But then why didn’t the drug improve their sleep? These studies relied on subjective measures of sleep, and ramelteon has a poor track record on subjective outcomes. In primary insomnia, it improved subjective sleep onset by only 4 minutes over placebo and objective sleep onset by 9 minutes. 

 showed the reverse pattern, improving subjective onset by 14 minutes but objective onset by only 4 minutes (placebo, by the way, is no dud, and improved sleep onset by 8 to 20 minutes).

One thing to take away from this is the importance of setting realistic expectations when starting patients on ramelteon. This hypnotic is not like the others: It is relatively nonsedating and has no anxiolytic, amnestic, or rewarding effects. On the one hand, those qualities improve on its safety, but they are unlikely to endear it to patients with BD, who often want a hypnotic to quiet the anxious, racing thoughts that rev up as they try to fall asleep. Ramelteon will do none of that, but nor will it cause patients to fall, overuse their medication, or engage in complex sleep behaviors like cooking or driving in the middle of the night. One positive aspect that most patients appreciate is the lack of tolerance and withdrawal with ramelteon. Rather than wearing off, ramelteon’s sleep benefits built up over weeks to months in some studies.

While ramelteon is a melatonin agonist, dark therapy is a behavioral treatment that enhances endogenous melatonin by keeping patients in a pitch-dark room overnight. Dark therapy was developed by Thomas Wehr, MD, who speculated that evening darkness might improve sleep and mania in the same way that morning light improves 

 and circadian rhythms. In the 1990s, he recruited normal participants with mild sleep problems to the National Institute of Mental Health, where they stayed in a pitch-dark room overnight from 6:00 pm to 8:00 am. After a few weeks of this dark therapy, their sleep improved.

 Next, he turned his attention to BD, and found that the same protocol stabilized refractory rapid cycling.

Further studies supported Wehr’s observation, but it was not until the discovery of blue light–blocking glasses that dark therapy became practical for everyday use. In theory, the physiologic changes associated with total darkness might be achieved by 

, because the receptor that regulates melatonin secretion—melanopsin—responds only to the blue spectrum. The hope in that theory is that patients might be able to practice dark therapy while still being able to see in the evening.

Psychiatrist James Phelps, MD, first tested that hope in private practice, and his results were later confirmed in a randomized, placebo-controlled trial in Norway. For the entire evening from 6:00 pm to 8:00 am, patients hospitalized with acute mania wore blue light–blocking glasses or, if sleeping or trying to sleep, stayed in a pitch-dark room without the glasses. Within a week, their 

 improved with a large effect size (1.86) compared with a placebo group that wore gray glasses.

The dark therapy protocol can be gradually relaxed after recovery, allowing patients to put the glasses on a few hours before bed to prevent future episodes. That relaxed protocol also improves the sleep, according to 3 randomized controlled trials in primary insomnia. Wearing blue light–blockers 1.5 to 3 hours before bed helped patients fall asleep earlier and stay asleep longer, and improved sleep quality as well as mood and 

 However, blue light blockers do not have a strong sedative effect. In line with their circadian mechanism, they improve the regularity of sleep more than they improve subjective measures of insomnia.

A critical step in dark therapy is finding glasses that filter close to 100% of blue light. Lenses that were tested in clinical trials include Uvex Skyper S1933X, Uvex Ultra-spec 2000 ($10 to $15) and, for more comfort at a higher price, glasses at lowbluelights.com ($50). More information on the nuts and bolts of dark therapy is available in the Psych Pearls podcasts from August and October 2021.

Cognitive behavioral therapy for insomnia (CBT-i) is thought to work by stabilizing the circadian system, making it a natural fit for mood disorders. In unipolar depression, CBT-i improves mood and sleep, but the therapy is often avoided in BD because it requires patients to limit their time in bed, raising concerns that this sleep deprivation could trigger mania. In 2015, Allison Harvey, PhD, and colleagues at the University of California – Berkeley modified the CBT-i protocol to include a built-in safety valve for BD (CBT-iBD). The newer therapy limits bed restriction to no fewer than 6.5 hours.

CBT-iBD also includes techniques to address common circadian rhythm abnormalities in BD, such sleep inertia (a prolonged sense of grogginess in the morning) and nocturnal hyperactivity. To counter these sleep-disrupting tendencies, patients develop a wake-up routine encompassing bright light and energizing activity, and an evening wind-down routine in which the lights are dimmed and 

To test the therapy, Harvey recruited 58 patients with stable BD but active insomnia and randomized them to CBT-iBD or a psychoeducational therapy. At the end of the 8-week therapy, patients in the CBT-iBD group were sleeping better compared with controls, but more profound changes came later. After 6 months, those who learned CBT-iBD had an 8-fold reduction in mood problems, spending an average of 3.3 days in a mood episode vs 25.5 days for controls.

Later, Bryony Sheaves, DClinPsy, BSc, CPsychol, and colleagues adapted CBT-iBD for patients with schizophrenia, major depression, and BD in an inpatient crisis unit. The 2-week program improved sleep and well-being, and it hastened discharge by 8.5 days compared to treatment as usual.

It can be difficult to find therapists who practice CBT-insomnia, but the core program is available through a prescription app (Somryst) or a free, VA-sponsored app (CBT-i Coach). These programs can be adjusted for BD with the modifications described above.

Dark therapy and CBT-i are safe in the young and old, and a few tips can help adapt these treatments for different ages. Adolescents often have severe night-owl tendencies, which can be corrected by having the patient wake up 15 to 30 minutes earlier each day and wearing blue light–blockers in the early evening (eg, 5:00 pm to 8:00 pm). Napping is common in older adults but is discouraged in the CBT-i protocol. One compromise is to have the patient eliminate naps during the therapy, and then gradually add them back in once regular sleep is restored. Then they can continue the naps as long as they do not cause a relapse into insomnia. Finally, for patients of all ages who are afraid of the dark, there are nightlights that emit zero blue light (at lowbluelights.com and Amazon).

Although no hypnotics are FDA approved in children and adolescents, lithium and several antipsychotics (eg, quetiapine) are approved for them. In the elderly, the risks of falls and cognitive impairment have placed most hypnotics on the “inappropriate” list of the Beers criteria, although ramelteon is well studied in older adults and approved by the Beers.

Treating insomnia in BD is both an art and a science, requiring practitioners to balance the patient’s goal of rapid sedation with the more therapeutic approach of retraining the circadian rhythm. Circadian therapies like ramelteon, dark therapy, and CBT-insomnia have a slow build, but they promise more lasting and substantial benefits for mood and sleep than fast-acting hypnotics.

is the Mood Disorders Section Editor for 

, Editor in Chief of The Carlat Psychiatry Report, and director of the Mood Treatment Center. The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for The Depression and Bipolar Workbook and from W.W. Norton & Co for

 Bipolar, Not So Much: Understanding Your Mood Swings and Depression.

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Long-term symptomatic status of bipolar I vs bipolar II disorders.

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3. Schaffer CB, Schaffer LC, Miller AR, et al. 

Efficacy and safety of nonbenzodiazepine hypnotics for chronic insomnia in patients with bipolar disorder.

4. Sabe M, Kashef H, Gironi C, Sentissi O. 

Zolpidem stimulant effect: induced mania case report and systematic review of cases.

Prog Neuropsychopharmacol Biol Psychiatry.

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Interventions for sleep disturbance in bipolar disorder.

The average patient with bipolar disorder struggles with sleep disorders. Here's how you can help. 

New Directions for Insomnia and Bipolar Disorder

There is increased recognition of sex differences in the epidemiology and phenomenology of 

. For example, compared to males, females have a slightly lower incidence of the disorder, a later age of onset, and more depressive symptoms.

 Such sex differences may be mediated, in part, due to neuroprotective effects of estrogen.

 By contrast, findings regarding sex differences in cognition in schizophrenia are inconsistent.

 Insomnia is also common in the clinical course of schizophrenia.

 In the general population, insomnia is associated with greater cognitive impairment, but its association (and potential sexual dimorphic effect) in schizophrenia is less clear.

“Ms Smith” is a 50-year-old Caucasian female with a 20+ year history of schizoaffective disorder, bipolar type, and a remote history of a cerebellar hemorrhagic stroke. She has been on a stable dose of antipsychotic medication for the past 10 years, prior to which a clozapine trial was discontinued due to tolerability and adverse effects. She chronically sleeps 3 to 5 hours per night, with both initial and terminal 

. She has chronic auditory hallucinations, thought insertion, and persecutory beliefs. She also has chronic cognitive impairment, thought to be in part due to not only her chronic psychotic illness, but also a sequela of the past cerebellar infarct. She graduated with a 2-year technical degree after high school. She has completed different forms of the Digit Symbol Coding test at multiple outpatient psychiatric clinic visits over the years, with a mean (SD) score of 31±4. A trial of adjunctive 

 for residual positive symptoms of psychosis was discontinued due to exacerbation of cognitive impairment.

Zhu and colleagues investigated sex differences in insomnia and 

 in a large sample of Chinese patients with chronic schizophrenia.

 They recruited 718 patients (480 males and 238 females) with chronic schizophrenia from 2 psychiatric hospitals and 397 healthy controls (169 males and 228 females) without a personal or family history of psychiatric or neurological disease. Inclusion criteria for patients were age 17 to 70, Chinese Han ethnicity, DSM-IV diagnosis of schizophrenia, and stable antipsychotic dose for > 6 months. Patients were excluded if they had a history of neurological disease, severe medical comorbidity, head injury, pregnancy or lactation, or history of drug or 

Insomnia was assessed as both a categorical (yes/no) and a continuous measure with the Insomnia Severity Index (ISI). Symptoms were rated using the Positive and Negative Syndrome Scale (PANSS). Cognition was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The authors used 2 x 2 ANOVA (insomnia x sex) and Spearman correlation coefficients to investigate sex differences in clinical variables in patients with and without 

The mean subject age was 46. There was a significantly increased prevalence of (categorical) insomnia in females versus males with schizophrenia (25.6% versus 18.3%, OR=1.54). Females with schizophrenia also had significantly higher PANSS total and subscale scores. Males with schizophrenia had higher (better) RBANS total, visuospatial/constructional, and language scores than females. In both males and females with 

, patients with (categorical) insomnia had higher PANSS scores than those without insomnia. By contrast, there was no difference in RBANS scores in males with versus without insomnia. However, females with insomnia had lower RBANS total and subscale scores. As a continuous measure, ISI scores were significantly, negatively correlated with RBANS total scores, language, attention, and delayed memory scores in males (ρ=-0.14 - -0.12 for each). By contrast, ISI scores were significantly negatively correlated with RBANS total scores (ρ=-0.18) and immediate memory (ρ=-0.19) scores in females.

The authors concluded that females with schizophrenia had an increased prevalence of insomnia and greater 

 than males. They also found sex differences in correlations between insomnia and cognition in these patients. Study strengths included the large cumulative sample size. Study limitations included the cross-sectional study design and the nonstandardized antipsychotic (and other) medications in the study sample. Future studies should consider associations between insomnia and cognition using a longitudinal design and also in first-episode and antipsychotic-free patients with schizophrenia.

Findings support evidence for sex differences in insomnia and cognition in patients with schizophrenia. Given associations with more severe symptoms and greater cognitive impairment, insomnia represents an important potential treatment target in this patient population.

is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

Sex and gender differences in schizophrenic psychoses.

Gender differences in schizophrenia and first-episode psychosis: a comprehensive literature review.

Oestrogens, prolactin, hypothalamic-pituitary-gonadal axis, and schizophrenic psychoses.

Prevalence of insomnia and clinical and quality of life correlates in Chinese patients with schizophrenia treated in primary care. 

Sex difference in association between insomnia and cognitive impairment in patients with chronic schizophrenia.

Thinking about sex and sleep in schizophrenia: Researchers performed a large cross-sectional study of sex differences in insomnia and cognition in chronic schizophrenia.

Sleep Disorders