Hero

Videos

Slideshows

Articles

Podcasts

Poll

“Ms Washington” is a 52-year-old African-American female with schizophrenia and no previous suicide attempts. Her psychotic disorder has been stable on quetiapine 200 mg at bedtime, with no psychiatric hospitalizations in the past 20 years. She has a history of episodic 

, which is currently treated with quetiapine and trazodone. In response to multiple recent stressors—including financial, transportation, and medical work-up for possible colon cancer—and in consultation with her psychiatrist, her quetiapine was increased over 1 month to 400 mg at bedtime due to worsening paranoia and insomnia. Subsequently, she overdosed on multiple, unspecified medications at home in a 

. She woke up the next morning, did not seek any medical attention, and did not tell anyone about the overdose until she revealed this information to her psychiatrist at an outpatient visit about 6 weeks after the attempt.

Insomnia and suicide ideation/behavior/death (SIB) are common in psychiatric disorders. Among psychotropic medications, there is evidence that clozapine and 

 have antisuicidal properties. Clozapine is the only antipsychotic with an indication for suicide prevention in schizophrenia from the US Food and Drug Administration (FDA).

 In the International Suicide Prevention Trial (InterSePT),

 insomnia was significantly less common in patients treated with clozapine versus olanzapine, consistent with evidence that sedation is a common adverse effect of clozapine.

 Similarly, there is evidence for antisuicidal properties of lithium.

 Although sedation is reported less frequently with lithium compared with other psychotropics, there is evidence for potential beneficial effects of lithium on sleep.

 Although the mechanisms underlying antisuicidal properties of clozapine and lithium remain unclear, effects on insomnia and sleep behavior may play a role. No previous studies have investigated associations between insomnia and SIB in patients taking antipsychotics and mood stabilizers.

 investigated the prevalence of spontaneously reported psychiatric 

 (ADRs) of insomnia and SIB in adults for other second-generation antipsychotics (SGAs) and mood stabilizers compared to clozapine and lithium.

The authors included all reports in the US FDA Adverse Event Reporting System (FAERS) publicly available database from inception in 1968 through February 2021, for which either a second-generation antipsychotic or mood stabilizer was the suspected agent of a psychiatric adverse event in adults aged 18 to 64. Data on total psychiatric adverse events, as well as insomnia and SIB adverse events were extracted. Data were combined for both generic and brand formulations, as well as oral and long-acting injectable forms of each SGA.

For each agent, the authors calculated the proportion of ADRs for insomnia and SIB by dividing the number of insomnia and SIB ADRs by the total number of psychiatric ADRs, respectively. They then calculated reporting odds ratios (rORs) and 95% confidence intervals (95% CIs) for insomnia and SIB ADRs relative to clozapine (for SGAs) and lithium (for mood stabilizers). Finally, they calculated bivariate correlations between the insomnia rOR and the SIB rOR.

Ten different SGAs (clozapine, olanzapine, paliperidone, risperidone, lurasidone, brexpiprazole, aripiprazole, asenapine, ziprasidone, and 

) and 5 different mood stabilizers (lithium carbamazepine, 

, oxcarbazepine, and lamotrigine) with at least 500 psychiatric ADRs were included in the analyses. For SGAs, insomnia ADRs comprised 11% and SIB ADRs comprised 23% of the total psychiatric ADRs. Compared to 

, all of the other SGAs were associated with a significantly increased reported odds of insomnia (rOR=2.41-9.70) and SIB (rOR=1.18-2.72). After excluding 1 extreme outlier (quetiapine), the insomnia and SIB rORs for each SGA were correlated at the trend level (r=0.66, p=0.053).

For mood stabilizers, insomnia ADRs comprised 7% and SIB ADRs comprised 32% of the psychiatric ADRs. Compared to lithium, there was a significantly increased reported odds of insomnia (rOR=1.66) for lamotrigine, a nonsignificantly increased reported odds of insomnia for the other mood stabilizers (rOR=1.06-1.23), and a significantly increased reported odds of SIB (rOR=1.17-1.70) for all other mood stabilizers. The insomnia and SIB rORs for each mood stabilizer were significantly, positively correlated (r=0.97, p=0.005).

The authors concluded that, compared with clozapine and 

, other SGAs and mood stabilizers, respectively, were associated with increased reported odds of insomnia and SIB, and the insomnia and SIB rORs were positively correlated for each medication class. Limitations of public pharmacovigilence data include that the FDA does not verify reports submitted to FAERS. Also, given the prevalence of insomnia and SIB in patients taking SGAs and/or mood stabilizers, it is also possible that some adverse events were misattributed to the drug rather than the illness itself. Individual level data in the FAERS database are limited, which could shed light on other potential confounding or moderating factors.

The present study is consistent with previous evidence for antisuicidal properties and potential beneficial effects on sleep for clozapine and 

. Findings raise the possibility that beneficial effects on sleep as one potential pathway underlying the antisuicidal properties for these agents, which warrant investigation in longitudinal studies. Findings also affirm the use of clozapine and lithium in relevant patient populations at high risk for suicide.

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.

Managing suicide risk in patients with schizophrenia.

2. Meltzer HY, Alphs L, Green AI, et al. International Suicide Prevention Trial Study Group. 

Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT).

Clozapine in the treatment of refractory schizophrenia: a practical guide for healthcare professionals.

4. Antolín-Concha D, Lähteenvuo M, Vattulainen P, et al. 

Suicide mortality and use of psychotropic drugs in patients hospitalized due to bipolar disorder: a Finnish nationwide cohort study.

5. Geoffroy PA, Samalin L, Llorca P-M, et al. 

Influence of lithium on sleep and chronotypes in remitted patients with bipolar disorder.

Lithium carbonate: effects on sleep patterns of normal and depressed subjects and its use in sleep-wake pathology.

Insomnia and suicide as reported adverse effects of second-generation antipsychotics and mood stabilizers.

All in a good night’s sleep? Researchers performed a pharmacovigilance study of second-generation antipsychotics and mood stabilizers as the suspected agent of psychiatric adverse drug reactions (insomnia and suicide/ideation/behavior/death).

Insomnia and Anti-Suicidal Properties of Clozapine and Lithium

, both chronic and acute, often interferes with sleep. Sleep interruptions and the side effects of pain medication are among the most commonly described disruptive interactions between pain and sleep. Bad dreams, which can be more difficult to study objectively than sleep disorders, are frequently associated with stress, anxiety, depression, and psychiatric and emotional disorders.

 Bad dreams are also associated with physical pain. The implications of this relationship are important, as bad dreams have been shown to have a substantial impact on sleep quality and restorative sleep. The disruptive effects of bad dreams can impact several important life issues, including mood, 

Recent research is beginning to shed a light on the complex relationships between pain and bad dreams. Postsurgical frightening dreams have been reported, especially among children.

 These dreams are thought to be short-lived, without a strong rate of recurrence, and are thought to be possibly associated with the effects of anesthesia, unfamiliar surroundings, and anxiety about surgery. Bad dreams during the perioperative timeframe are not thought to have a substantial impact on quality of life. Chronic pain, however, is also associated with bad dreams, and this can have more disruptive implications on day-to-day life.

Musculoskeletal pain, which is a particularly common type of pain, can develop as a result of serious injuries and associated 

 (PTSD), but it more often occurs in the absence of severe physical issues or associated psychological sequelae. A recent observational study published in 

 compared the frequency of self-reported bad dreams and nightmares between participants who had chronic musculoskeletal pain and a control group who did not have this type of pain. Over the course of a month, 44% of 191 participants with established pain reported bad dreams, compared to 7.3% of the 191 controls. The researchers also measured several other variables, including vitamin D and calcium levels, anxiety, and depression. Low vitamin D and calcium, as well as the presence of anxiety or depression, were all correlated with bad dreams and with musculoskeletal pain.

While the conclusions do not definitively point to a strong independent correlation between pain and pain bad dreams, these results do support the idea that there could be a possible connection.

Research has also examined the relationship between 

 and bad dreams. Migraines are widely considered to be complex experiences that include pain but are not limited to pain. Bad dreams are associated with 

, and the relationship seems to be bidirectional. Some small studies have suggested that bad dreams can occur during an ongoing migraine episode, and research also suggests that some people may have bad dreams prior to the onset of the painful portion of a migraine episode, possibly as part of a migraine prodrome.

The mechanism behind the relationship between pain and bad dreams is not fully established, but these types of 

 generally occur during the rapid eye movement (REM) sleep stage. Researchers suggest that the either the dream content is altered by pain experiences, or that the recollection or amount of REM sleep is altered by the physiological effects of pain on the brain.

 Understanding the mechanism can help guide treatment strategies. And, for some patients, their own awareness of the interactions between pain and their dreams can help encourage them to report their experiences and to seek treatment.

 and bad dreams have an impact on sleep quality, as well as on daytime sleepiness. Patients who experience chronic pain conditions, including migraine, often experience daytime fatigue and increased sleepiness around the time of the episodes. These symptoms are independent of sleep disturbance, but they can be exacerbated by sleep disturbances. Nightmares and bad dreams can further contribute to daytime sleepiness and diminished quality of life for people who are living with chronic pain. Patients who have bad dreams can experience anxiety about the dream content or may become concerned about whether the dreams are a reflection of their own mental health. These issues highlight the importance of adequate pain treatment for people who have pain conditions. Yet some medications can further interfere with sleep, making treatment less than straightforward.

Pain treatment can be intimidating for patients who are concerned about side effects and addiction. While these are valid concerns, there are many safe options for managing pain besides oral medication, including injections, patches, meditation, and cognitive behavioral therapy, among others. All of these can help alleviate the risk of bad dreams that can worsen sleep quality and quality of life for patients who have chronic pain.

is Associate Editor Humanities in Neurology, Clinical Assistant Professor Case Western Reserve University School of Medicine, Div. of Medical Education, and Editor in Chief Emeritus of 

1. Vanek J, Prasko J, Ociskova M, et al. 

Nightmares affect the experience of sleep quality but not sleep architecture: an ambulatory polysomnographic study.

3. Eriksson M, Nilsson U, Bramhagen AC, et al. 

Self-reported postoperative recovery in children after tonsillectomy compared to tonsillotomy.

Nightmares and bad dreams among individuals with musculoskeletal pain: a link to vitamin D and calcium.

Nightmares in migraine: a focused review.

Pain can have a substantial impact on sleep quality and quality of life. 

Pain on the Brain: The Relationship Between Bad Dreams and Chronic Pain

Controlled breathing exercises can be a solution or an adjunctive treatment for some people who have primary insomnia. 

 is a common problem, affecting most adults at some point in their lives. Chronic insomnia and temporary bouts of insomnia can both affect total sleep time, restorative sleep, mood, and daytime sleepiness. These issues can also lead to disrupted sleep schedules—with unwanted daytime naps, 

, decreased productivity, and a feeling of being unrested.

Many patients who cannot fall asleep or stay asleep will report their symptoms to their primary care doctor, and those who have idiopathic 

 may be referred to a psychiatrist or a sleep specialist when first line and second line therapies are ineffective. As more patients are learning about the harms of chronic use of various sleeping pills, some are asking for nonpharmacological therapies to aid in the treatment of insomnia or will agree to try a nonpharmacological management approach when it is suggested by their doctor. While dysregulated breathing is a key component of obstructive sleep apnea and central sleep apnea, breathing irregularities have not been widely considered a significant component of 

 to help patients with insomnia is based on several underlying issues: the role that the autonomic nervous system plays in sleep and the relationship between insomnia and depression or anxiety. Breathing exercises are considered an adjunct in management anxiety and depression, which are common comorbidities of insomnia. Researchers have proposed that hyperarousal and chronic sympathetic hyperactivation and/or parasympathetic hypoactivation could disrupt a number of sleep features, such as normal sleep onset latency, sleep quality, and sleep duration.

 A large review study noted that people who had insomnia were found to have a range of different alterations in their autonomic activity.

 This subclinical autonomic dysfunction is one of the potential explanations for why breathing exercises may have a beneficial impact on insomnia.

A few studies have examined the effects of controlled breathing on insomnia. One study, for example, assessed the effects of presleep breathing exercises on a small group of participants who had self-reported insomnia. During the study, the participants learned how to do slow paced breathing exercises for 20 minutes before going to sleep. After implementing the exercises, participants experienced a number of positive outcomes.

 Sleep onset latency, number of awakenings, and awakening time during sleep were decreased, and sleep efficiency was increased. Based on these observations, the researchers proposed that people who have insomnia may have disordered autonomic function, suggesting that deliberate control of breathing could help regulate autonomic function in patients who have insomnia, and that this could have potentially played a role in the observed symptom improvement.

Another experiment assessed the effect of a yoga breathing technique on healthcare professionals during the 

. Participants initially rated their sleep through a series of questionaries before learning breathing techniques that are part of a specific type of yoga practice.

 After using the breathing techniques on a regular basis, the participants experienced improvements in self-reported sleep and quality of life measures.

While these and other similar studies are generally small, a variety of different types of breathing exercises with varying schedules (during the day or right before sleep) seem to have a positive impact on sleep, without side effects. Controlled breathing and deep breathing may help to promote sleep initiation.

 The effect on sleep initiation would not, however, explain the benefits of 

 that are done during the day. There seems to be a positive effect of breathing exercises on insomnia that reaches beyond sleep initiation. Sympathetic hyperactivation is generally associated with rapid, shallow breathing, while the parasympathetic state is associated with slower, deeper breathing, and the interplay between these aspects of the autonomic nervous system is generally expected to have effects that last several hours.

Breathing exercises can be a safe and useful adjunct in the treatment of insomnia. People can learn to use controlled breathing on a regular basis or can add these techniques to a more comprehensive sleep regimen as a way to help manage bouts of insomnia. For patients who want to gain a sense of personal control over their sleep, such exercises may provide a good way to take part in their own management. Patients can learn breathing techniques by working with a therapist or by using videos or apps recommended by their doctor. Because deep breathing techniques have also been shown to help alleviate anxiety, which is both a cause and an effect of insomnia, these types of exercises can reduce insomnia and its effects with a multipronged approach.

Self-regulation of breathing as an adjunctive treatment of insomnia.

2. Nano MM, Fonseca P, Vullings R, Aarts RM. 

Measures of cardiovascular autonomic activity in insomnia disorder: a systematic review.

Efficacy of paced breathing for insomnia: enhances vagal activity and improves sleep quality.

4. Divya K, Bharathi S, Somya R, Darshan MH. 

Impact of a yogic breathing technique on the well-being of healthcare professionals during the COVID-19 pandemic.

New research suggests deliberate control of breathing could help regulate autonomic function in patients who have insomnia.

Controlled Breathing Exercises as an Adjunctive Treatment for Insomnia

Antidepressant augmentation is a common practice, and there are many strategies from which to choose. The 

 recommends a menu approach that encourages patients to collaboratively choose an option that best fits their needs.

 In addition to psychotherapy and lifestyle approaches like aerobic exercise, they recommend augmentation with:

1. Natural treatments: omega-3 fatty acids, L-methylfolate, or light therapy

2. Antipsychotics: aripiprazole, risperidone, or quetiapine

3. Antidepressants: bupropion, imipramine, or mirtazapine

When rapid relief is the priority, an antipsychotic might be the best choice. For favorable tolerability, there is bupropion or a natural therapy, and lithium has strong antisuicide effects, if that is a concern. But what if insomnia is the chief complaint? Mirtazapine is tempting here, but this medication carries a risk of weight gain and did not perform well in several recent, well-designed augmentation trials.

 Instead, a standard hypnotic may be a good option when patients continue to have depression and insomnia on an antidepressant, but not just any hypnotic.

Eszopiclone: The Science Behind Its Potential Effect on Depression

In the early 2000s, a group of sleep researchers set out to investigate whether hypnotics could improve mood in patients with depression and insomnia. The results did not pan out exactly as expected, but they point the way toward a medication with unique potential in depression.

But first, investigators had to overcome a hurdle. At the time, it was thought that hypnotics might cause depression through their sedative effects. That concern was partly put to rest in a 1999 study that tested whether zolpidem could relieve selective serotonin reuptake inhibitor [SSRI]-induced insomnia in patients who had otherwise recovered on the antidepressant. The sleep problems improved with zolpidem and, to the investigators’ relief, the sedating medication did not worsen depression.

Buoyed by this result, the manufacturer of eszopiclone funded a large trial to see if depression might actually improve with their hypnotic. Five hundred and forty-five patients with depression and insomnia were randomized to receive either eszopiclone 3mg or placebo while simultaneously starting a trial of fluoxetine. As expected, the hypnotic improved sleep, but it also improved mood symptoms that were unrelated to sleep. Compared to placebo, those who received eszopiclone experienced a more rapid and complete recovery from depression.

The same group repeated the study with zolpidem ER in a large trial of similar design. Once again, the hypnotic improved sleep, but this time there was no change in mood.

 Replication in China brought the same negative results, and last year zolpidem failed again to lift mood or reduce suicidality when added to an SSRI in a randomized trial of patients with depression, insomnia, and suicidality.

Meanwhile, eszopiclone repeated its success, improving mood and insomnia in 2 additional trials, 1 of which involved peri- and postmenopausal women with insomnia and depressive symptoms.

 Generalized anxiety disorder also improved when eszopiclone was added to an SSRI in a large manufacturer-supported trial that replicated the design of eszopiclone’s pivotal depression trial.

Both the zolpidem and eszopiclone studies involved many of the same investigators, who had pursued this work with the idea that any hypnotic that improved sleep would indirectly improve mood. But to this day eszopiclone remains the only hypnotic with distinct antidepressant effects (ramelteon has mild preventative benefits in bipolar disorder but is not known to treat depression).

 Whether this is a statistical fluke or a true difference is difficult to say, as eszopiclone has not gone head-to-head against other hypnotics in depression. However, eszopiclone does have a unique mechanism of action that might explain its antidepressant effects. To understand that we need to turn to the GABAA receptor.

Compared to the benzodiazepines, the z-hypnotics have more limited effects on GABAA, which is thought to explain why they treat sleep but not anxiety. Specifically, the z-hypnotics are selective for the sleep-inducing GABAA α-1 subunit, while benzodiazepines have additional effects on the α-2 and -3 subunits that are involved in anxiety and depression. But eszopiclone is an exception. It acts at all of the α subunits, and may actually be a little more selective for the anxiolytic α-2 and-3.

 This effect is furthered by eszopiclone’s active metabolite, desmethylzopiclone, which is a selective partial agonist at α-2 and -3 with very little α-1 activity (that is a good thing, as it would otherwise cause a lot of daytime sedation).

 In animal models, desmethylzopiclone reduced anxiety without causing sedation or motor impairment.

 Its effects in humans are not well described, but the trials above give us a hint, and the company that launched eszopiclone has patented this metabolite as a potential anxiolytic.

In this way, eszopiclone resembles the benzodiazepines, which have been used to treat depression and hasten the response to antidepressants in over 3 dozen controlled trials.

 In most of those trials, their antidepressant effects were independent of their anxiolytic effects, just as eszopiclone treated symptoms of depression that were unrelated to sleep.

Despite this research, benzodiazepines are not used routinely for depression because of their risk of tolerance and abuse. Those risks may also apply to eszopiclone, but the trials above provide some reassurance. In several of them, eszopiclone was replaced with a placebo after 2 months of treatment without any loss of the antidepressant and anxiolytic gains. Nor was there any rebound insomnia and, in some studies, it stabilized sleep patterns in a way that continued after the hypnotic was stopped.

Does all this elevate eszopiclone to the level of antidepressant augmentation? Possibly. It does have more positive results than some the augmentation strategies that are endorsed by evidence-based guidelines.1 But there are 2 caveats. First, eszopiclone was only studied in patients with comorbid insomnia, but this is not a major hurdle as it is the rare patient with depression who does not struggle with sleep (about 15%).

 More significantly, eszopiclone was started in tandem with an antidepressant in these augmentation trials, so we do not know if it could turn things around when added later, after a few antidepressant failures.

When selecting a hypnotic in depression or generalized anxiety disorder, eszopiclone should be on the list. The treatment need not be long-term. Most patients were able to taper off the hypnotic after recovery. To bolster those odds, start out with the expectation of short-term use and guide the patient toward 

is the Mood Disorders Section Editor for 

 He has written several books on mood disorders, most recently

 with his cohost Kellie Newsome, PMH-NP. The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for

The psychopharmacology algorithm project at the Harvard South Shore Program: an update on unipolar nonpsychotic depression.

Mirtazapine augmentation: Running low on rocket fuel.

. September 2019. Accessed August 27, 2021.

3. Asnis GM, Chakraburtty A, DuBoff EA, et al. 

Zolpidem for persistent insomnia in SSRI-treated depressed patients.

Efficacy and tolerability of Z-drug adjunction to antidepressant treatment for major depressive disorder: a systematic review and meta-analysis of randomized controlled trials.

5. McCall WV, Benca RM, Rosenquist PB, et al. 

Reducing suicidal ideation through insomnia treatment (rest-it): a randomized clinical trial.

6. McCall WV, Blocker JN, D'Agostino R Jr, et al. 

Treatment of insomnia in depressed insomniacs: effects on health-related quality of life, objective and self-reported sleep, and depression.

7. Joffe H, Petrillo L, Viguera A, et al. 

Eszopiclone improves insomnia and depressive and anxious symptoms in perimenopausal and postmenopausal women with hot flashes: a randomized, double-blinded, placebo-controlled crossover trial.

. Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder.

Melatonin receptor agonists-ramelteon and melatonin-for bipolar disorder: a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials.

. Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics.

Molecular actions of (S)-desmethylzopiclone (SEP-174559), an anxiolytic metabolite of zopiclone.

12. Carlson JN, Haskew R, Wacker J, et al. 

Sedative and anxiolytic effects of zopiclone's enantiomers and metabolite.

13. Benasi G, Guidi J, Offidani E, et al. 

Benzodiazepines as a monotherapy in depressive disorders: a systematic review.

Wisniewski SR, et al. Insomnia in patients with depression: a STAR*D report.

A hypnotic might be a good option for augmenting depression treatment, but which hypnotic has the best evidence for efficacy? 

An Overlooked Strategy for Antidepressant Augmentation?

 What advice do you have for community-based psychiatrists treating patients with narcolepsy? What would you tell them? How should they interact with sleep specialists?

 They need to find 1 they’re comfortable with. They need to start thinking about sleep issues on any of their resistant psychiatric patients, whether it’s depression, anxiety, or schizophrenia. The studies on people who have schizophrenia and narcolepsy have shown that those patients often don’t respond well to antipsychotics. But if you diagnose the narcolepsy and you treat them with a little stimulant and an antipsychotic, they get better. When they’re seeing resistant anything, they should be thinking sleep disorders.

It’s important to not assume that it’s probably their medicines or that they’re way better than they used to be. How much better is better enough for these patients? If they come in and you think they’re schizophrenic and you’ve gotten them to this point and they’re doing better, is that as good as it gets if they’re sleepy every day or they sleep 12 or 13 hours a day? They may not be hallucinating, but they’re still sleeping a lot and napping every day. It could be the medicines, but could we get them better?

It’s the same thing with depression and treating depressed patients. You’re often treating their cataplexy whether you know it or not. They may not come and say, “I have sleepiness, I have cataplexy,” because they’ve been on antidepressants for a long time. The only symptom you may get in a depressed patient at a psychiatric office is the excessive daytime sleepiness. Educating all the providers, even the therapist, about this excessive daytime sleepiness or whatever they call it—I’m tired, I can’t wake up, I can’t get going in the morning—is important. This symptom needs to be a serious symptom that we address, and we look for sleep apnea, narcolepsy, and what medicines we’re using.

 One hundred percent yes. Exactly. Not everyone is going to be doing an Epworth Sleepiness Scale in their office—not a psychiatrist, not a neurologist. But if you can identify a patient, they’re not going to say, “I’m sleepy,” but they may say, “I’m tired, I’m fatigued, I’m unmotivated.” They have inertia. That’s your chance to step in and look for something else that might be going on. It doesn’t mean narcolepsy. You could have sleep apnea that’s impacting you to a degree. But the point is to make an intervention at that point with our resistant patients. You can really make a difference in their lives.

 Yes. Restless leg syndrome is a huge 1 in the psychiatric world. Not only do the patients have it, but a lot of our medicines increase it. When they take the medicine is so important. Psychiatrists at community-based facilities need to be looking at that, what medicines you’re giving them, and when you’re giving them. Are they taking any vitamins? Is there magnesium? There are a lot of behavioral treatments for every 1 of our sleep disorders.

 Absolutely. It’s important to work together with psychiatrists, neurologists, and primary care physicians in the community. As you said, this is why I love doing these programs. We’re educating and getting the word out there to keep an eye out for patients in your practice who likely have sleep disorders. We know that probably 1 of 2 people walking on the street has a sleep issue of some sort.

 They’re prevalent, and in today’s day and age and our society that we live in with screens and our lifestyle, it’s gotten worse.

 Absolutely. And insomnia. I do a lot of insomnia. But it’s not just a medicine—an Ambien or Lunesta treatment. There are usually so many other reasons. Even the patients with narcolepsy have a lot of insomnia and disrupted sleep. I’ve had a sleep physician tell a patient, “You can’t have narcolepsy, because you have insomnia,” and I’m like, “That’s not true. You have disrupted sleep and disrupted wake. What you have with narcolepsy is a disruption.”

 It’s not just your daytime sleepiness. It happens at night too, because your brain is confused about sleep and wake. Absolutely. Great points.

We’re at the end, and I want to thank you for participating in this program. I really appreciate the dialogue we’ve had. Hopefully this will help our psychiatrist colleagues and other doctors in identifying narcolepsy and psychiatric comorbidities and getting these patients adequately treated. Thank you for watching this 

 program. It’s been an excellent discussion. Hopefully you’ll find it useful to your clinical practice. Thank you so much.

Dr Stultz has disclosed that she serves as a consultant on the advisory board for Harmony Biosciences and that she receives support in her role with the speaker’s bureau for Harmony Biosciences and Jazz Pharmaceuticals.

Dr Singh has disclosed that he serves as a consultant and receives support in his role with the speaker's bureau for Jazz Pharmaceuticals and Harmony Biosciences. 

In this custom video series, Debra Stultz, MD, and Haramandeep Singh, MD, share advice for community-based psychiatrists on the management of narcolepsy.

Narcolepsy Treatment Advice

 What are some of the common challenges and unmet needs you face when treating patients with narcolepsy?

 Education is the key. We need more resources for the families and patients that are written on their level, because the family members really don’t understand it. The patients will come to the office, and they may get the diagnosis. They get excited and start looking it up online. The family members may not always do that. Just the other day, a patient I’ve treated for some time for narcolepsy kept saying, “My husband doesn’t understand it.” I said, “Bring him in. This is perfect, we’ll do a little family therapy thing.” It was helpful, but it’s going to take time. We need more education and support for the other people involved in the narcolepsy world.

We need more education for primary care providers and even sleep doctors about when to order tests for narcolepsy, the symptoms to look for, and what to order. We need to start with the patient, look at their family, and look at their providers. We need a lot for this diagnosis to keep moving forward.

 No doubt. I like that point about primary care providers and even sleep specialists, who just say, “When can we think about making the diagnosis, getting the MSLT [multiple sleep latency test] done, and even looking at ancillary symptoms of narcolepsy—sleep paralysis, hallucinations, automatic behaviors, cataplexy—and documenting that in your chart?” It’s the little things like how long you’ve been sleepy. It doesn’t take a lot. It just takes that extra few minutes to explore a little more of your patient and what’s happening for them. Those are the unmet needs.

We talked about how we definitely have options in terms of treatment, and those are going to continue to expand, which is great. We’re looking at other options coming out in the future as well that may be useful.

 Yes. We should be screening for all sleep disorders when the patient first comes in the sleep laboratory, and not just snoring. We need to carefully look at restless leg syndrome, whether you’re kicking in your sleep, whether you have sleep paralysis and the hypnagogic hallucinations. We should have a good sleep screener, and the sleep history should be an important part of dictating even a regular sleep study. Oftentimes, the primary care doctor says it’s excessive daytime sleepiness, and the patient thinks they’re getting an extensive sleep review. If they just get back a piece of paper that says they don’t have sleep apnea, then where do they go?

Or maybe they’ve had an MSLT before and they say, “I had that test, I don’t have narcolepsy.” That’s not true either. MSLTs are like EKGs [electrocardiogram]; it’s not 1 and you’re done. You wouldn’t say, “I had an EKG about 10 years ago. My heart is fine.” You’d say, “You need to do another EKG.” The same is true of you needing another MSLT. We need to look at this again. We need to make sure we study you during the MSLT off certain medicines, or considering certain medicines if you’re still on them, and that may not have been done when they had an MSLT before.

 Great points. I often comment that we’re doctors, so we should be looking at the patient holistically and not just following 1 test. You come back with a negative test, and that’s where our patients get lost. They’re like, “I’m still tired. It’s 10 years later, and now I’m depressed and unmotivated, and I can’t focus.” This is where we miss the boat. We have to holistically look at the patient and use the test as a guidance. Maybe we need to repeat the test and think about other options. I appreciate those points.

In this custom video series, sleep specialists discuss common unmet needs and challenges when treating patients with narcolepsy.

Unmet Needs in the Treatment of Narcolepsy

 In terms of the roles and responsibilities of the neurologists and psychiatrists in narcolepsy treatment, what are some of the challenges that arise in having multiple perspectives on 1 patient? If the psychiatrist sees a patient for comorbid depression, what are some challenges that come with that?

 I’m sorry, did you mean challenges with different providers?

 Yes, with a neurologist and psychiatrists who may have different perspectives on the same patient.

 Sometimes there are some issues. You have to have somebody who’s the captain of the ship when you’re treating narcolepsy. That’s probably the person who diagnoses it if they’re comfortable with treating that and using the medicines. Some of my colleagues who are sleep doctors or pulmonary doctors don’t do a lot of narcolepsy and are more than happy to send the patient with narcolepsy or insomnia to me because I’m used to these medicines and how we prescribe them. In that case, they’re saying, “You do this, and if you need me, let me know.”

I’ve also had sleep doctors refer to me and say, “I want you to treat the depression before I treat the narcolepsy,” I say, “We probably should go in with both at the same time. I’ll treat the depression, and I’ll treat with something that might help some of these symptoms, but we need to treat the narcolepsy too.” Sometimes there’s thinking, “What can we do to get this patient better faster?” In my opinion, it’s usually treating both.

If there’s cataplexy and other hints of neurological things, then we need a neurologist to help us look for secondary causes of narcolepsy that we might not be thinking about. Do they have MS [multiple sclerosis] or Parkinson’s disease? One of my other favorite things to monitor for is head injuries. A lot of our patients with narcolepsy have a past history of some head injuries. Did that play in? Having a neurologist on board is very helpful. We have to decide who’s going to treat what so that we’re not doubling up on medications, or even with the primary care provider.

One of the things I’d mention about pitolisant, when we were talking about the first case, is that we always have to tell the patients, “You need to tell me if you change any medicines, and you need to tell your primary care providers that you’re on this medicine.” I had a patient who was on an antidepressant and was on the lower dose of pitolisant. She was doing great, so I didn’t see her for 6 months. When she came back in, I asked, “How are you doing?” She said, “I’m doing pretty well, but I had some depression, so my primary care provider started Wellbutrin.” Then we had the patient on 2 antidepressants and pitolisant that could affect the 2D6. It’s also important to let the primary care doctor know what you’re doing and who’s doing what so that we’re not all throwing things in there.

 Great point. That communication among other providers is so important. I like the comment about the captain of the ship. If you’re the expert in treating this, then it’s your responsibility to take the reins and say, “I’m going to treat the narcolepsy.” I have a lot of doctors who I work with who are psychiatrists and neurologists. When they’re treating something else, whether it’s depression, anxiety, or whatever else is going on for the patient, they should continue that role, but let me be the 1 who’s treating the narcolepsy. The education, communication, and dialogue among doctors is so important.

 We need psychiatrists and therapists involved in treating narcolepsy because we often have a patient who’s had symptoms and excessive daytime sleepiness or cataplexy for years, and it’s greatly affected their life, failures, disappointments, and not understanding. They may get the diagnosis of narcolepsy and be all excited that somebody figured it out. Initially, it’s relief. But then they start looking at the way life could have been better had somebody caught it 10 years ago. They look at their relationships and the ballgames they missed for 8 to 10 years of their kids’ childhood. There’s a grieving process that happens with narcolepsy. They may have depression for years for a variety of reasons, but then there’s some stuff that goes on once you get the diagnosis and you start treating. Having a psychiatrist or therapist on board for treating narcolepsy is invaluable for the sleep physician or neurologist who’s treating a patient with narcolepsy with just the medicines.

 Absolutely, I agree 100%. The more you get in terms of mental health providers who can help in managing a chronic condition in general is a huge benefit.

 That’s right. These patients with narcolepsy will wake up and suddenly have more energy, and they’re excited about life. They start trying to make some changes and will do this and do that. Everybody else in their world is like, “We’ve been doing fine on our own here.” The change and relationship issues are often hard. There’s a whole dynamic to the diagnosis of narcolepsy for not only the patient, but also the significant other, children, and even work.

 Good point. Many times, I’ve heard the patient with narcolepsy get branded as being lazy or not motivated. That branding gets put into the family member and the spouse. They have to have the education. Therapy is such a useful part of that process as well in helping them with the family situation.

 Right. The self-esteem stuff starts at a very young age. These sleepy kids go to school and have trouble with grades, get to school late, miss school a lot, or get in trouble because they’re fussy and irritable. The self-esteem stuff starts then.

 Exactly. As we know, that’s when it starts. We know that the amount of time it takes for the diagnosis of narcolepsy is often 15 to 20 years before the patients are recognized. Their symptoms started way back when. We know with sleep disorders it takes a long time in general, but with narcolepsy especially it takes a long time.

In this custom video series, Haramandeep Singh, MD, and Debra Stultz, MD, discuss the roles and responsibilities of sleep specialists, neurologists, and psychiatrists in the management of narcolepsy.

Role of Specialists in Narcolepsy Management

 When you’re considering choosing a treatment regimen, what patient factors and symptoms come into play? How is the patient involved in that process in terms of choosing a treatment for them?

 That’s very important. The way I choose a lot of times is based on what the coexisting thing is. If they use alcohol, then I’m going to stay away from sodium oxybate, unless they’re drinking once or twice a month. Then you can hold your Xyrem that night and still be OK. But if they’re drinking pretty regularly, that’s not a medicine I’m going to use.

If they have a lot of anxiety, then I’m going to try to steer away from the stimulants that might cause more anxiety. If they have coexisting depression and cataplexy, I may go with more of the traditional antidepressants that might treat the symptoms. If they have trouble remembering to take medicines, then I’m going to use something that’s once a day in the morning. If they say, “I’m so rushed when I get out, I probably wouldn’t remember a morning medicine,” then I’m going to start looking to use 1 of the bedtime medicines that could treat the sleepiness and cataplexy. If they have cataplexy, as we talked about earlier, pitolisant or sodium oxybate would be a good choice because that would kill 2 birds with 1 stone. My decision is often based on what else is there.

 Absolutely. Having that conversation with a patient in terms of their other symptoms and their lifestyle is really important.

 It’s exactly as we saw in that 20-year-old college-age student who is probably going out a few times a week, so it makes it clear for us that we want to try to use something that’s got less of a controlled substance. We want to avoid sodium oxybate. But then there’s the patient who has had a multitude of trials with modafinil, with stimulants. They tolerate them; they’re still sleepy. We know that with some of our narcoleptics, they need to be on 2 or 3 medications to get relief. Sometimes we’ll add pitolisant, or Wakix, on top of that, or add sodium oxybate, or taper them off 1 and get them on that. I appreciate that, in terms of the conversation you’re having with them.

 Yes. The majority of our patients with significant narcolepsy end up on a combination of medicines. When you think about it, we’re looking at different neurotransmitters and symptoms. We mentioned the birth control pill earlier. You can have trouble with the birth control pill with not only pitolisant but also modafinil and armodafinil. So maybe Sunosi is the choice there. If it’s a young woman of reproductive age, I’ll have the talk about that. They may be fine with taking that medicine while practicing safe sex, so we’re fine. But I have that discussion.

It depends on age, sex, who’s taking care of it, and who else lives in the family. I have patients who have narcolepsy, but also have a substance abusing child living at home. In those situations, I don’t want anything else. Even though they’re going to try to lock it up, I don’t want anything else there that can contribute. Even if my patient isn’t a substance abuser, I usually ask who’s at home. I want to make sure we’re not leaving medicines around. That could play into the decision as well.

 Absolutely. That conversation is so important in terms of delineating your therapy. Another area is Sunosi is cleared by the kidney, so if you’ve got a patient who’s on multiple other medications catalyzed by the liver, that’s another area where you could think about Sunosi. I’ve had young women with young children at home who may not want to take so much sodium oxybate at night, [to the point that] they feel as if they can’t wake up in the mornings. All these things, and having that conversation, are really important.

The good thing we find in today’s day and age, and what we’ve lacked in the past, is that we have options. This is an area in which we’ve finally gotten more standard of care. The AASM, the American Academy of Sleep Medicine, has made it clear that these are standards of care we should consider when we’re treating our patient.

 Yes. We’ve been so lucky in the field of narcolepsy. I’ve been doing sleep medicine for years, and narcolepsy has been my favorite disorder to treat. But for years, nobody was talking about it, and we didn’t have a lot of options. Then it just exploded with options. The wonderful thing about that is we’re getting the word out about narcolepsy to patients. Even if the providers are not as informed about narcolepsy, the patients are coming in saying, “I might have this,” or “Can we try this medicine?”

 I love what it’s done to education of society.

In this custom video series, experts in sleep medicine discuss patient factors and symptoms they consider when selecting optimal treatment regimens for patients with narcolepsy.

Sleep Disorders