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“Sleep problems are understudied,” Ellen Lee, MD, told attendees at the 2021 American Psychiatric Association (APA) Annual Meeting. “They’re underdiagnosed and undertreated in people with mental illness.” Thus, Lee encouraged clinicians to screen for sleep problems, because sleep “is a modifiable and important target for intervention.” Lee, along with other colleagues, shared insights and preliminary research results on how sleep may impact mental health and psychiatric disorders.

Sleep problems affect between 30 and 80% of individuals with schizophrenia and are associated with lower quality of life and poorer cognitive and frontal lobe functioning, explained Lee, assistant professor in residence in the Department of Psychiatry at the University of California at 

 In as-yet unpublished research, Lee found that sleep apnea is associated with increased inflammation, while higher subjective reports of sleep quality are associated with lower levels of inflammation. Since inflammation is also associated with 

 treating sleep problems could also improve the symptoms of mental illnesses.

Beyond schizophrenia, sleep issues also appear in mood disorders like depression. Stephen Smagula, PhD, presented research on possible links between morning activation deficits and depression among family members caring for patients with dementia.

Older individuals with depression often report difficulty getting up and active in the 

 Morning activation deficits are sometimes thought to be immutable (some individuals are just not morning people), but in functional magnetic resonance imaging readings, dementia caregivers with depression showed higher resting-state amygdala-PCC connectivity, which is associated with stress, fear, and 

 “Although this is speculative,” Smagula cautioned, “it seems plausible that the non-morning type caregivers are doing behaviorally disengaged, emotion-focused coping. So put another way, some caregivers might wake up, feel overwhelmed, say ‘Expletive! I’m going back to bed.’”

This raises the possibility, according to Smagula, who is assistant professor of psychiatry and epidemiology at the University of Pittsburg, that “instead of treating the depression and hoping the morning activation deficit goes away, we could be targeting the morning activation deficit to treat the depression.” Clinicians could consider treatments such as activity scheduling, which would get the caregivers up and moving, increase their light exposure, decrease fragmented sleep, and limit the time they spend ruminating—all of which could improve their depressive symptoms.

Sleep also affects cognition, especially in older adults. Ruth O’Hara, PhD, presented initial data on the impacts of delta activity at sleep onset (DASO). Study participants with DASO demonstrated better affective function overall and over time, which led O’Hara to conclude that testing DASO or other variables may help clinicians predict patients’ cognitive futures. “We think that characterizing sleep dysregulation in older adults may in fact identify valuable biomarkers,” explained O’Hara, who is the Josephine Q. Berry Professor of Psychiatry and Behavioral Sciences at Stanford University. They could “help us predict cognitive decline and onset of dementia, as well as predicting affective dysfunction.”

1. Cohrs S. Sleep disturbances in patients with schizophrenia: impact and effect of antipsychotics. 

2. Keshavan MS, Montrose DM, Miewald JM, Jindal RD. Sleep correlates of cognition in early course psychotic disorders. 

3. Bromundt V, Köster M, Georgiev-Kill A, et al. Sleep-wake cycles and cognitive functioning in schizophrenia. 

4. Lee EE, Ancoli-Israel S, Eyler LT, et al. Sleep disturbances and inflammatory biomarkers in schizophrenia: focus on sex differences. 

5. Smagula SF, Capps CS, Krafty RT. Evaluating the timing of differences in activity related to depression symptoms across adulthood in the United States. 

6. Smagula SF, Karim HT, Ibrahim TS, et al. Resting-state function connectivity associated with being a "morning-type" dementia caregiver and having lower depression symptom severity. 

Sleep problems are understudied, underdiagnosed, and undertreated. 

Dreaming of New Treatments

Between mid-February and mid-March 2020, the number of sleep prescriptions in the United States rose by 14.8%. The increase may be due to the pandemic, says Manoj Malhotra, MD. Based on his experience, he says “the current environment, with myriads of shifts in our day-to-day lives, is a perfect storm for sleep challenges.”

In this Mental Health Minute, Malhotra explains how to distinguish between a general lack of sleep and chronic insomnia, and how to treat the latter.

 is vice president, United States medical affairs for the neurology business group at Eisai.

Have you seen more patients with sleep problems during the pandemic? 

Share comments with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

Key considerations for healthcare providers seeking to manage their patients’ insomnia.  

The COVID-19 Pandemic Is a Perfect Storm for Sleep Challenges

The US Food and Drug Administration (FDA) recently accepted the new drug application (NDA) for Idorsia’s investigational dual orexin receptor antagonist, daridorexant, designed for the treatment of 

“I’m very happy that this first regulatory hurdle is behind us,” said Jean-Paul Clozel, MD, Chief Executive Officer of Idorsia. “This was a huge NDA and the team has done an excellent job in preparing the dossier, on which the FDA can judge the properties and merits of daridorexant. We now stand-by to work with the FDA to answer any questions that might arise concerning the effect of daridorexant on sleep, daytime functioning, and its safety profile.”

Daridorexant targets overactive wakefulness associated with insomnia by blocking the activity of orexin, has a rapid onset, and lasts long enough to cover the night without any next-morning residual sleepiness. According to data from the phase 3 registration program, daridorexant is the first insomnia treatment to show statistically significant and clinically meaningful improvements in daytime functioning, sustained over time, as well as sleep during the night.

“While we designed daridorexant to have the optimal profile for a sleep medicine, I am none-the-less stunned by the results. Once approved, by providing daridorexant to the millions of patients with insomnia, Idorsia will have a major impact on this medical, social, and economic problem,” Clozel said. “It has struck me particularly in these times of confinement that we are living through, that sleep problems are a major issue and require an extremely safe and effective drug that can be used by the many. With these results Idorsia is entering into a new era; less than 3 years since its creation, Idorsia is taking a huge step forward in delivering on the vision to become a fully-fledged biopharmaceutical company.”

Adverse events included headache, somnolence, fatigue, dizziness, and nausea, although the incidence of somnolence was low and did not increase with daridorexant 50 mg when compared with placebo.

Idorsia submitted the NDA on January 8, 2021 and anticipates a US launch in the first half of 2022, should approval be received.

1. Idorsia Pharmaceuticals. FDA accepts the new drug application for review of Idorsia’s daridorexant for the treatment of adult patients with insomnia. 

https://www.globenewswire.com/news-release/2021/03/10/2190042/0/de/FDA-accepts-the-new-drug-application-for-review-of-Idorsia-s-daridorexant-for-the-treatment-of-adult-patients-with-insomnia.html

2. Idorsia Pharmaceuticals. Idorsia announces positive results in the first Phase 3 study of daridorexant with improved overall sleep and daytime performance of patients with insomnia. News release. April 20, 2020. 

https://www.idorsia.com/media/news-details?newsId=2284972

This investigational dual orexin receptor antagonist improved sleep overnight and daytime functioning. 

Insomnia Treatment Without Daytime Sleepiness

Teralyn Sell, PhD, MS, NCC, LPC, provides tips on what late night snacks could disrupt sleep patterns. 

Blueberries Treat Depression, With a Catch

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.

The key to better sleep? Stabilizing blood sugar. 

Goodnight, Sugar: Foods to Improve Sleep

Over 30 million Americans live with diagnosable chronic insomnia. It can impair their everyday functions when awake and affect their mood. Chronic insomnia is also a risk factor for other chronic illnesses and psychiatric disorders (up to 40% also have depressive symptoms).

Existing pharmacological treatments are designed for short-term use, which may not be enough to combat a long-term illness. In this Mental Health Minute, Yuri Maricich, MD introduces Somryst, the first FDA-authorized prescription digital therapeutic (PDT) for treating chronic insomnia. It is a 9-week program that is accessible through mobile devices, including smartphones and tablets. He discusses two studies on the effectiveness of this new PDT.

(Note: in the video, Dr Maricich says that the FDA authorized Somryst in 2023. The FDA authorized it in 2020.)

A new treatment has been found effective for treating a common sleep disorder.

Introducing the First FDA-authorized Prescription Digital Therapeutic for Chronic Insomnia

Dr Richard Bogan discusses the ins and outs of sleep and psychiatric disorders and shares his thoughts about a recent FDA approval of XYWAV (calcium, magnesium, potassium, and sodium oxybates), indicated for the treatment of narcolepsy. XYWAV, 

, is "the first FDA approved new treatment option indicated for both cataplexy and excessive daytime sleepiness in people living with narcolepsy in more than 15 years." 

 is Medical Director, SleepMed of South Carolina; Chief Medical Officer, SleepMed, Inc; Associate Clinical Professor, University of South Carolina School of Medicine; and Associate Clinical Professor, Medical University of South Carolina in Charleston, SC.

A sleep specialist highlights what to watch out for in your patients.

Intersection of Sleep and Psychiatric Disorders

There is overwhelming evidence that sleep and circadian rhythm disturbances and disorders are prevalent in psychiatric patients and associated with worse outcomes. Nonetheless, the associations between sleep/rhythms and psychiatric disorders are not well understood, and additional research is necessary to mechanistically link sleep dysfunction to mental illness. Furthermore, despite the fact that there is evidence that treating sleep and behavioral rhythms improves psychiatric outcomes, training in sleep medicine for psychiatrists is often insufficient. As a result, sleep and rhythms are often not adequately assessed or appropriately targeted in the clinical practice of psychiatry.

The articles in this Special Report address key issues. While the association between insomnia and psychiatric disorders has long been recognized, more recent evidence demonstrated a strong relationship between insomnia and suicidal ideation and behaviors across the lifespan, as discussed by Wilfred R. Pigeon, PhD, and Todd M. Bishop, PhD. Thus, patients with insomnia, even in the absence of severe psychiatric symptomatology, should be screened for suicide, and treatment for insomnia should be considered to reduce suicidal ideation.

Circadian rhythm abnormalities are also prevalent in psychiatric patients, although they have received less attention than sleep problems. Practitioners may not always recognize circadian abnormalities in their patients and may lack the training and knowledge to provide adequate chronotherapy; for example, delayed onset due to a shifted circadian rhythm may be mistaken for sleep onset insomnia if a careful sleep history is not obtained. Helen J. Burgess, PhD, and Leslie M. Swanson, PhD, discuss the association between delayed sleep phase and mood, anxiety and substance abuse, as well as the increased risk of psychiatric illness related to irregular sleep timing. Their expert tips and guidance in screening patients for circadian rhythm abnormalities as well as stabilizing and entraining rhythms with light therapy, melatonin, and behavioral interventions is most useful.

Similarly, the article by Ellen E. Lee, MD, discusses how sleep can affect psychiatric disorders by increasing inflammation and oxidative stress. Her group has shown that patients with serious mental illnesses have increased levels of pro-inflammatory cytokines. Other studies have shown that sleep deprivation, insomnia, and obstructive sleep apnea are not only more common in patients with psychiatric disorders, but they are also associated with worse outcomes and contribute to inflammation. Conversely, treatments for insomnia and sleep apnea have been shown to have positive effects on psychiatric symptomatology. Taken together, these findings suggest mechanistic pathways by which sleep disorders, inflammation, and psychiatric illness are linked.

In summary, there is increasing evidence that disturbed sleep and circadian rhythms impact the risk for developing psychiatric disorders, and inflammatory processes are suggested as one possible mechanism of this well-established relationship. Sleep and circadian rhythm disturbances are modifiable factors, and while data on the effects of sleep disorder treatment on inflammatory processes is preliminary and limited, treating sleep and behavioral activity rhythms have consistently shown positive impact on mental health outcomes. Most importantly, treatment of sleep dysfunction may reduce suicide risk.

Future research is necessary to better understand the mechanistic pathways and to improve the availability of evidence-based treatments of sleep disorders in patients with mental health disturbances. Hopefully this Special Report will help you better understand some of these relationships and will lead to improved patient outcomes.

Dr Benca is Chair of Psychiatry & Human Behavior in the School of Medicine at University of California, Irvine. She reports that she has served as a consultant to Eisai, Genomind, Jazz, and Merck.

The associations between sleep/rhythms and psychiatric disorders are not well understood. With additional research we can better address key issues and improve patient outcomes.

Sleep Disorders: A Wake-Up Call

The steadily rising rate of suicide in the US is a vexing public health crisis. Between 2007 and 2017, suicide was the 10th leading cause of death, claiming the lives of nearly half a million people.

 It is perhaps even more striking that suicide is the fourth leading cause of death for individuals aged 35 to 54 as well as the second leading cause for those aged 10 to 34. Based on 2018 epidemiologic data, 1.4 million adults per year make a non-fatal suicide attempt and 10.4 million have serious thoughts of suicide.

 Among the many risk factors for suicidal thoughts and behaviors, one that consistently emerges as an independent risk factor is sleep disturbance (broadly defined) along with the specific sleep disorders of insomnia, nightmares, and sleep apnea.

One reason that this sleep-suicide relationship is so important is that sleep disorders represent a modifiable risk factor. As noted a decade ago, several sleep medicine interventions can potentially make a difference in the lives of individuals who may be on a trajectory to suicide.

It has yet to be firmly established if improving sleep actually reduces suicide. However, in a recent analysis of a large medical record study, it was observed that having a sleep medicine consultation was a protective factor for subsequent suicide attempts among those with a sleep disorder.

 There are also some indications that cognitive-behavioral therapy for insomnia (CBT-I) reduces suicidal thoughts.

Mechanisms by which improved sleep may reduce risk are also putative. Indirectly, we can say with some certainty that sleep disorders (eg, insomnia, sleep apnea) are strongly related to the development and course of depression and their reversal improves mood. Other hypothesized mechanisms through which poor sleep may be associated with suicidal thought and behavior include increased impulsivity, emotional dysregulation, and impaired executive functioning, each of which may be reversed with improved sleep.

What, then, are actionable items for the clinician wishing to address the sleep-suicide relationship? We present three focal areas:

• Suicide assessment and safety planning

• Sleep treatment options in the suicidal patient

Given the high prevalence of insomnia in psychiatric populations and the ability of psychiatrists to fully manage insomnia (as opposed to sleep apnea), the primary focus of treatment options is for insomnia disorder.

Often a sleep disturbance is identified in an initial psychiatric evaluation or in the normal course of a treatment episode by either a general screening question, “Do you have trouble sleeping?” or a direct patient complaint “My sleep is terrible.” We strongly recommend leveraging the use of standard depression screening tools to identify sleep complaints. For example, item 3 of the Patient Health Questionnaire-9, which probes for insomnia and hypersomnia has been found to be a good screen for clinically meaningful insomnia.

 An endorsement of 1 or higher on this 0-3 Likert-type scale item can be followed with questions to quickly assess for the possible presence of either of the two most common sleep disorders (ie, insomnia and sleep apnea).

Alternatively, the 7-item Insomnia Severity Index and the 8-item Stop-Bang Questionnaire can be used to assess sleep problems.

 Both are efficient and well-validated instruments for detecting probable insomnia and apnea, respectively.

Even among mental health providers a frequent barrier to reliable suicide risk assessment is the clinician’s comfort with asking the patient about suicide. It is, therefore, worth highlighting the importance of asking patients about all aspects of suicide risk. These inquiries range from asking whether the patient is thinking of killing themselves to inquiring whether they have made a plan or started gathering the means to attempt suicide.

For those involved in graduate medical education or residency training, the coupling of traditional didactic suicide prevention training with videotaped standardized patient interactions can optimize supervision around suicide assessment.

 Having a well-established safety protocol and clinical staff that are trained to use it will free you and your staff to conduct more thorough assessments with the confidence that a plan is in place to handle risk, should it emerge or worsen. For the same reason that we ask patients to write down their safety/crisis plan, it is best to have these safety protocols in writing so that they can be easily referred to when the situation to use them arises (see 

Safety contracts or no-harm contacts between patient and provider, which were widely used, are of limited value. Instead, the use of a more involved safety planning or crisis response planning process is recommended.

 Safety planning and crisis response planning differ slightly but share many common features (

While the presence of a sleep complaint or sleep disorder may increase the risk of suicide compared with the absence of sleep disturbance in otherwise similar patients, it does not significantly change the approach to the treatment of suicidality. One important exception is that patients with current prescriptions for sedative-hypnotics have at their disposal a potential means of suicide (ie, overdose); this needs to be evaluated as part of safety or crisis planning. Otherwise, the recommended treatments for suicide prevention can be utilized for suicidal patients with sleep disorders.

Cognitive behavioral therapy for suicide prevention (CBT-SP) is the only intervention with enough empirical evidence to warrant a strong recommendation; no other nonpharmacologic or any pharmacologic treatment for suicide prevention has enough evidence to receive more than a weak recommendation for its use.

 In contrast, there are very well-supported, strongly recommended treatments for several sleep disorders.

Generally, standard sleep interventions can be delivered to patients endorsing suicidal thoughts with few modifications, provided that an office/clinic safety protocol and a patient-specific crisis plan are in place. For instance, suspicion of apnea would lead to a referral for a diagnostic evaluation at a sleep center. For nightmares, which can present as idiopathic nightmares but are more commonly associated with PTSD, two main nightmare interventions are considered to have the strongest evidence base: the use of the Î±1-adrenergic agonist prazosin and imagery-rehearsal therapy. 

For insomnia disorder, CBT-I, is the recommended first-line treatment.

 CBT-I typically consists of 6 to 8 weekly individual or group sessions including sleep psychoeducation, stimulus control, sleep restriction, sleep hygiene, and cognitive therapy and tends to be more enduring than pharmacological interventions. It has been effectively delivered in numerous comorbid populations and can have positive effects on mood.

Numerous pharmacologic interventions for insomnia are recommended as second-line treatment when there is no response to CBT-I or it is contra-indicated. Despite clinical practice guidelines, pharmacotherapy for insomnia is far more common than CBT-I or related approaches and may be preferred by some patients. Hypnotics can be administered safely to suicidal patients with insomnia as has been done with zolpidem ER, which may reduce suicidal ideation.

 The prescribing physician must be cognizant that: many hypnotics come with FDA black-box warnings; overdose is the most common means of suicide attempt; and off-label use of medications with sedating properties (eg, trazodone, tiagabine) have a significant harm-to-benefit profile.

Psychiatrists are in an excellent position to manage deprescribing hypnotics in the not uncommon presentation of persistent severe insomnia despite multiple sedating medications taken at night. We find many patients who present with major depressive disorder, insomnia disorder, and suicidal ideation who have been prescribed a nightly antidepressant (eg, 40-mg fluoxetine) are also using a non-benzodiazepine receptor agonist (eg, 10-mg zolpidem) and 100-mg trazodone or 150-mg quetiapine fumarate while supplementing with an over-the-counter formulation at well-above the recommended dosage (eg, diphenhydramine, doxylamine, melatonin). Discontinuation plans may precede or be combined with CBT-I, however, the latter may be more advantageous.

In addition, when patients present with insomnia and a co-occurring condition (eg, depression, posttraumatic stress disorder, chronic pain) there is good evidence that CBT-I can be combined with psychological or pharmacologic therapy that targets the comorbid condition. For example, CBT-I can be combined with an antidepressant in depressed patients or with trauma-focused treatments for patients with PTSD. With appropriate safety planning, patients who also endorse suicidal thoughts can be similarly treated.

We recognize that a full course of CBT-I may not fit every psychiatrist’s clinic model and/or they have few appropriate referral options. In such cases, very viable alternatives exist. Shorter versions of CBT-I have been utilized with good effect, as have single components of CBT-I (eg, stimulus control, sleep restriction).

Sleep hygiene, which is often delivered with minimal follow-up, is insufficient for many patients. If sleep hygiene is delivered as the primary method of addressing insomnia, it may be improved by systematically incorporating specific goals (eg, reduce caffeine intake, limit napping), daily tracking, and problem-solving during follow-up sessions.

Treatment outcomes for sleep disorders are enhanced by regular assessment, follow-up, and/or titration of treatment. For example, ask patients to complete a sleep diary each morning and to meet with you on a weekly or biweekly basis in order to interpret the results and adjust the sleep schedule accordingly. Likewise, patients starting positive airway pressure (PAP) for sleep apnea will nonetheless benefit from psychiatric consultations early in the treatment process to encourage and support treatment adherence. Moreover, patients may benefit from the use of apps and web-based platforms that aid in monitoring behavior and logging sleep diary data as well as providing supplemental education (eg, CBT-I Coach: 

www.veterantraining.va.gov/insomnia/index.asp

Although a myriad of pressing clinical issues face a patient with suicidal ideation, incorporating sleep assessments and interventions into the clinical care plan has multiple advantages. First, improving sleep not only provides immediate relief of sleep related symptoms, it may also lead to improvements in co-occurring pathology such as depression. Second, sleep disorders represent a comparatively low stigma entry point into treatment, and a successful course of sleep-focused therapy can instill confidence in the patient that therapy works and is worth the investment. Finally, sleep disorders have been linked to increased suicide risk and, thus, their treatment may reduce this risk.

Dr Pigeon is Professor of Psychiatry and Public Health Sciences, University of Rochester Medical Center, Rochester, NY, and Executive Director, Center of Excellence for Suicide Prevention, Canandaigua VA Medical Center, US Department of Veterans Affairs; Dr Bishop is Assistant Professor of Psychiatry, University of Rochester Medical Center, and Health Science Specialist, Center of Excellence for Suicide Prevention, Canandaigua VA Medical Center. Dr Pigeon reports that he is a consultant for CurAegis Technologies, Inc; Dr Bishop reports no conflicts of interest concerning the subject matter of this article.

1. Centers for Disease Control and Prevention, National Centers for Injury Prevention and Control. Web-based Injury Statistics Query and Reporting System (WISQARS).

2. Substance Abuse and Mental Health Services Administration. 2018 National Survey on Drug Use and Health.

3. Pigeon WR, Pinquart M, Conner K. Meta-analysis of sleep disturbance and suicidal thoughts and behaviors. 

4. Bishop TM, Ashrafioun L, Pigeon WR. The association between sleep apnea and suicidal thought and behavior: an analysis of national survey data. 

5. Pigeon WR, Caine ED. Insomnia and the risk for suicide: does sleep medicine have interventions that can make a difference? 

6. Bishop TM, Walsh PG, Ashrafioun L, et al. Sleep, suicide behaviors, and the protective role of sleep medicine. 

7. Trockel M, Karlin BE, Taylor CB, et al. Effects of cognitive behavioral therapy for insomnia on suicidal ideation in veterans. 

8. Christensen H, Batterham PJ, Gosling JA, et al. Effectiveness of an online insomnia program (SHUTi) for prevention of depressive episodes (the GoodNight Study): a randomised controlled trial. 

9. MacGregor KL, Funderburk JS, Pigeon W, Maisto SA. Evaluation of the PHQ-9 item 3 as a screen for sleep disturbance in primary care. 

10. Morin CM. Insomnia: Psychological Assessment and Management. New York, NY: Guilford Press; 1993.

11. Chung F, Abdullah HR, Liao P. STOP-Bang Questionnaire: a practical approach to screen for obstructive sleep apnea. 

12. Cross WF, West JC, Pisani AR, et al. A randomized controlled trial of suicide prevention training for primary care providers: a study protocol. 

13. Department of Veterans Affairs and Health Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for the Assessment and Management of Patients at Risk for Suicide. 2019.

14. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. 

15. Qaseem A, Kansagara D, Forciea MA, et al. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. 

16. McCall WV, Benca RM, Rosenquist PB, et al. Hypnotic medications and suicide: risk, mechanisms, mitigation, and the FDA. 

17. McCall WV, Benca RM, Rosenquist PB, et al. Reducing suicidal ideation through insomnia treatment (REST-IT): a randomized clinical trial. 

18. Pigeon WR, Funderburk JS, Cross W, et al. Brief CBT for insomnia delivered in primary care to patients endorsing suicidal ideation: a proof-of-concept randomized clinical trial. 

19. Germain A, Moul DE, Franzen PL, et al. Effects of a brief behavioral treatment for late-life insomnia: preliminary findings. 

20. Morgenthaler T, Kramer M, Alessi C, et al. Practice parameters for the psychological and behavioral treatment of insomnia: an update: an American Academy of Sleep Medicine report. 

The steadily rising rate of suicide in the US is a vexing public health crisis. Among the many risk factors for suicidal thoughts and behaviors is sleep disturbance.

The Strong Relationship Between Sleep and Suicide

What do the following criminal cases have in common? In 1686 a Colonel Culpepper of King James’s Court not only shot a member of the guard, but shot his horse as well. In 1847 in Massachusetts, Albert Tirrell slit the throat of a female acquaintance with a razor and set the house on fire. In 1985 in Ontario, Canada, Kenneth Parks stabbed his mother-in-law to death and critically wounded his father-in-law. In 1997 in Phoenix, Arizona, Scott Falater stabbed his wife 44 times near their backyard pool and left her lying there. After he returned some 30 minutes later to find she was still alive, he retrieved work gloves from the garage and dumped her body into the pool. He then held her head under water. In 2008 in Wales, Brian Thomas choked his wife of 40 years to death while they were on vacation.

In all cases the defense claimed these criminal actions occurred while the defendant was in a sleepwalking state and amnestic of all behaviors. Four of the 5 cases resulted in acquittal or a special verdict. Only Falater was convicted; he is now serving a life sentence. These are only a few of the cases among more than 100 instances of apparent sleep-related violence that have been reported, most often in the legal literature, but more recently in the psychological literature as well. They include instances of homicide, assault, and sexual assault.

[[{"type":"media","view_mode":"media_crop","fid":"41453","attributes":{"alt":"Â© arda savasciogullari/shutterstock.com","class":"media-image media-image-right","id":"media_crop_6346265849796","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4374","media_crop_rotate":"0","media_crop_scale_h":"200","media_crop_scale_w":"105","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Â© arda savasciogullari/shutterstock.com","typeof":"foaf:Image"}}]]A brief history of sleepwalking

Historical reports of sleepwalking can be found from more than 1000 years ago. However, until recently these reports of nocturnal wandering included a number of now separately diagnosed sleep and neurological disorders. Alcohol intoxication, dissociative states, fugue states, epilepsy, REM behavior disorder (RBD), and many other disorders that occur at night were lumped together and labeled as somnambulism. Sleepwalking is now considered a non-REM parasomnia and is characterized along with sleep terrors and confusional arousals as a disorder of arousal.

 Other disorders such as nightmares and RBD occur during REM sleep and are etiologically and behaviorally distinct.

The scientific understanding of sleepwalking and related parasomnias has historically reflected the predominant beliefs of the time. Superstitions and religious beliefs defined sleepwalkers as possessed or demonic. In the 19th and first half of the 20th centuries sleepwalkers were said to be acting out dreams. And, as psychodynamic theories held that dreams often manifested psychological traumas, it was not difficult to divine the source of behaviors, violent or otherwise, that occurred during sleep.

A major Kuhnian-type paradigm shift in the theory of sleepwalking occurred in the 1950s and 1960s with the advent of electroencephalography (EEG) and sleep laboratories. The first major change was the identification of REM sleep and the further finding that if someone is awakened during REM sleep, chances are 80% or better that he or she will report a vivid, hallucinatory experience-what is generally called a dream.

 In addition, REM sleep is associated with a lack of voluntary muscle tone. Thus, the active dreamer is unable to somnambulate.

The brain state as characterized before 1957 was actually most consistent with a newly discovered sleep disorder-RBD-described in 1985.

 Patients with RBD have an intermittent loss of muscle atonia during REM sleep, most often because of encroaching slowly developing neuropathology, such as Parkinson disease or multiple system atrophy, that may take years or decades to fully manifest.

To the surprise of researchers, the first sleep laboratory studies performed starting in 1965 found that sleepwalking and related disorders-sleep terrors and confusional arousals-did not occur during REM sleep.

 Rather, they typically occurred in the first third of the sleep period during a time characterized by high-amplitude delta EEG waves: variously called deep sleep, slow wave sleep, stage 3 or 4 sleep and, now, N3 sleep. The complex behaviors followed a sudden arousal. For unknown reasons, the sleepwalker did not awaken completely but remained in a brain state that was neither awake nor asleep.

A “perfect storm” of sorts needs to occur for sleepwalking to take place. Research has shown that sleepwalking is most often associated with predisposing, priming, and provoking factors (3 Ps).

 However, we do not know why sleepwalking happens on a particular night and not on another when all 3 Ps are present.

Predisposing factors are genetic, and sleepwalking clearly runs in families. However, at least 3 different modes of genetic inheritance have been reported, and positive findings rarely exceed 50% in group studies.

 Thus, genetic research is not yet useful for clinical or forensic purposes.

In addition, there are priming factors. Many episodes of sleepwalking and sleepwalking-related violence follow periods of acute sleep deprivation. After acute sleep deprivation, rebound sleep often occurs. Deep sleep typically rebounds first, resulting in a higher than usual quantity or percentage of deep sleep. Rebound deep sleep may be associated with an increased threshold for arousal, perhaps providing an explanation for why sleepwalkers have difficulty awakening. Situational stress is another common priming factor that is often present along with sleep deprivation. Loss of a job, the night before an important test, relationship difficulties, etc, are usually easy to identify. However, the presence of predisposing and priming factors is not sufficient to cause sleepwalking: something must provoke or trigger the episode. Most often this is a sound or touch. Recent research has shown sleep-disordered breathing (eg, snoring, apnea) is often a trigger.8 Successful treatment of sleep-disordered breathing-continuous positive airway pressure or surgery-can dramatically reduce or eliminate episodes of complex sleep-related behaviors.

In addition to non-REM disorders of arousal, there are non-REM parasomnia subtypes: sleep-related eating, sexual behavior in sleep, sleep driving, and sleep-related violence. Many patients with one of these variants also have a current or past history of sleepwalking, confusional arousals, or sleep terrors.

In addition to possible genetic elements, neuroimaging studies have started to advance our understanding of the underlying pathology of sleepwalking. An important element to consider is the normal state of the brain during sleep. For all intents and purposes, the cortex is deactivated during sleep.

 However, its functions should not be necessary during sleep because incoming sensory stimuli are blocked or filtered at the level of the thalamus.

It should be noted that the amplitude of the slow, high-amplitude delta waves that characterize deep sleep is negatively correlated with the degree of deactivation. This information becomes important when we consider the findings of Bassetti and colleagues.

 These researchers triggered a sleep terror in a 17-year-old male while he was undergoing single-photon emission computed tomography neuroimaging. The results showed that the frontal cortex was deactivated, but incoming sensory stimuli were not blocked; as a result, some stimuli were reaching the deactivated cortex.

This study has not been replicated, but the results appear consistent with recent findings concerning brain function during sleep. States of consciousness have been found to be not unitary but overlapping. Many brain disorders, including sleepwalking, were hypothesized to be the result of dissociated brain functions.

 Research has demonstrated that both wake and sleep may occur in the brain simultaneously-“local sleep.”

 This suggests the neuropathology of the sleepwalker is functional or at least current neuroimaging technology is insufficient to detect any lesions or malformations. The functional problem appears to involve incomplete gating of incoming stimuli that might result in an arousal uninhibited by the cortex.

What behaviors might be expected in such situations? Behaviors related to basic impulses such as hunger, sex, and aggression might still be available. Other behaviors sometimes termed automatic behaviors might also be available. Can driving a car be an automatic behavior? Highway hypnosis aside-is a fully functioning cortex required for driving, walking, eating, or defending one’s self from a perceived aggressor?

Sleep-related violence is an interesting example of this odd brain state and to some degree lends support to the theories described above. There does not appear to be anything inherently violent about sleepwalkers. Cartoonish images of sleepwalkers moving about the house with arms outstretched, often grasping a knife while chanting “kill, kill, kill,” are not consistent with extensive scientific and clinical knowledge of sleepwalking. Rather, in nearly all cases reliably described, the victim of the violence most often seeks out or encounters the sleepwalker.

Family members or friends may simply encounter the sleepwalker in the hallway or elsewhere and not realize he is sleepwalking. More often, a family member attempts to prevent injury by blocking or grabbing the sleepwalker. This may set off a primitive, defensive form of aggression. With the cognitive parts of the brain deactivated, the sleepwalker cannot recognize the family member or friend. The eyes of the sleepwalker are open, although we do not know how well the eyes are functioning. The sleepwalker can navigate in familiar settings, but accidents are common.

 described a situation in which this type of defensive aggression was directly observed. During a sleep laboratory experiment, the researchers attempted to trigger episodes of complex sleep behaviors in clinically diagnosed sleepwalkers. Once deep sleep occurred, they presented acoustic stimuli that triggered complex behaviors-some research participants got out of bed and started to move around the sleep laboratory. This posed an unanticipated problem: how to ensure the safety of the sleepwalkers. Technicians entered the room and approached the sleepwalking subjects. They were met with violence, such as punches and kicks; one subject picked up a chair and threw it at the technicians. This suggests that under the right circumstances any sleepwalker can become violent.

The potential violence of patients who have RBD is completely different in both etiology and form.

 In RBD, the patients are in REM sleep when the violence occurs. It occurs because the usual REM sleep atonia is lost intermittently, which allows the patient to essentially act out the content of the dream. However, it is important to remember that the action remains within the dream world. While dreaming, the patients are not conscious of being in bed with a spouse sleeping nearby. Rather, their actions are those of the dream character. The accountant who is dreaming he is repelling pirates with a cutlass might accidentally punch his wife. It is unlikely that his wife was part of the dream scenario or that the punch was intentionally directed at her.

Forensically, both sleepwalking and RBD might result in violence without intention, planning, or culpability. Every year a dozen or more criminal defenses are based on the theory that the defendant was in the midst of sleepwalking or a related disorder when the criminal behavior occurred. There certainly are bona fide cases of sleepwalking violence that, depending on the jurisdiction, might fulfill the requirements of an insane or non-insane automatism.

Certainly mens rea cannot be present in someone who is not awake. For that matter, someone who is not awake cannot know right from wrong. The diagnostic and forensic evaluation of an episode of sleep violence can be problematic. Because sleepwalking is associated with amnesia of the episode, the patient/defendant cannot provide details. For the same reasons, the patient/defendant is not able to provide a direct memory of previous episodes. Any history provided is most likely to come from family or friends. However, the patient/defendant may be able to provide more circumstantial evidence. Awakening in a location other than the bedroom or unexplained damage or injuries may suggest something has happened during the night.

In forensic situations, malingering must also be considered part of the differential diagnosis. Sleepwalking must be carefully distinguished from other potential causes of nocturnal wandering. In recent years, there has been a concerted effort by some defense attorneys to suggest alcohol and even severe alcohol intoxication can be a trigger for sleepwalking behavior and not the direct cause of criminal behavior. This is considered junk science.

 The recently published International Classification of Sleep Disorders states that sleepwalking and related disorders should not be diagnosed in the presence of alcohol intoxication.

In the UK, Canada, and occasionally the US, the individual found to have been sleepwalking during the commission of a crime may be remanded to a hospital or more often to an appropriately trained physician, most often a psychiatrist. However, the state-of-the-art treatment of sleepwalking is straightforward and rarely requires a hospital stay.

First, attention must be paid to the most common priming factors: sleep deprivation and situational stress. A regular sleep-wake schedule with 7 or more hours of total sleep time is a good starting point. Brief awakenings scheduled to disrupt deep sleep are effective in children. Hypnosis has also been reported to be effective, and there may be similarities between the hypnotic state and the sleepwalking state. Elimination of triggering factors such as snoring or sleep apnea can be effective.

Assistance in dealing with situational stress is often required. Treatment with benzodiazepines is often effective for both sleepwalking and RBD; clonazepam remains the drug of choice. The occurrence of sleep-related violence may also be suppressed with these interventions, although this type of behavior rarely repeats itself and usually there is no continuing danger.

Sleep-related violence is a generally accepted variant of sleepwalking and related disorders. It may result in injury to self and others, and can have legal consequences. Sleepwalking may be treated by modifying potential priming and triggering factors, with or without medication. Sleep-related violence is likely to be reduced if family and friends take steps not to challenge the sleepwalker directly, although this cannot always be avoided because of safety concerns.

Dr Pressman is Clinical Professor of Medicine at Jefferson Medical College in Philadelphia, Clinical Professor at the Lankenau Institute for Medical Research in Wynnewood, PA, and Adjunct Professor at the Villanova University School of Law in Villanova, PA. He reports no conflicts of interest concerning the subject matter of this article.

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Here's a brief history of sleepwalking, associated factors, and pathology; sleep-related violence and forensic considerations; and management strategies.

Sleep-Related Violence

Parasomnias are undesirable physical, experiential, or behavioral phenomena that occur exclusively during sleep onset, during sleep, or during arousals from sleep. Their manifestations may be easily confused with psychiatric disorders when bizarre motor and/or emotional behavior is mistakenly interpreted as symptomatic of waking aberrance. For some, there may be associations with psychiatric disorders, their treatments, and/or their contribution to predisposition.

In DSM-5, the parasomnias are non–rapid eye movement (NREM) sleep arousal disorders (sleepwalking, sleep terror types), nightmare disorder (formerly known as dream anxiety disorder), and rapid eye movement (REM) sleep behavior disorder (RBD). (Interested readers may refer to the International Classification of Sleep Disorders, third edition, which describes parasomnias in more detail.

Underlying the various parasomnias is the fact that NREM sleep, REM sleep, and wakefulness are not mutually exclusive. Behavioral and electrophysiological components of each may separate and recombine in aberrant ways. For example, when concurrent components of NREM sleep and wakefulness occur, there may be variable juxtapositions or oscillations of consciousness, memory, motor, and/or autonomic activation that result in sleepwalking and sleep terrors. Similarly, complex dream enactment behavior can be liberated during spells of RBD in persons with skeletal muscle atonia.

Although not specified in DSM-5, the simplest of the disorders of arousal is confusional, hence disordered, arousal, which is partial awakening with periods of apparent confusion and inappropriate or absent responsiveness to others while in bed. There is typically amnesia for the event and minimal or no recall of dream mentation. This can evolve into spells including intense autonomic activation with vocalization, tachycardia, tachypnea, mydriasis, diaphoresis, and sleep terrors or sleepwalking.

A recent study found that confusional arousals occurred in 15.2% of a large community sample, and more than half reported at least one episode every week.

 Participants who reported confusional arousal had significant associated mood disorders, alcohol use disorders, panic disorder, PTSD, and generalized anxiety disorder, although no causal relationship was established. Of those who reported confusional arousal, 31.3% were taking a psychotropic drug, mostly an antidepressant. A smaller association was seen with hypnotic, anxiolytic, anticonvulsant, and antipsychotic agents. Other epidemiological evidence suggests some association between sleepwalking, major depression, and obsessive-compulsive disorder, although again with no established causal relationship.

 Generally, there is no need for interventions when confusional arousal occurs in the absence of other sleep disorders, such as obstructive sleep apnea, and without vigorous vocalization or motor activation.

An interesting variant of sleepwalking is sleep-related eating disorder, with episodes of eating during behavioral arousal from sleep without hunger or clearly established wakefulness. These eating episodes typically involve high-carbohydrate and fatty foods, often those that are not ordinarily consumed or toxic; binging is common. Psychiatrists must query patients receiving MAOIs and their families because of the risk of possible hypertensive crisis. Sleep-related eating disorder, in most cases, is distinct from the night eating syndrome, which is distinguished by evening hyperphagia with fully wakeful nocturnal eating.

Another variant of confusional arousals and sleepwalking is sleep-related abnormal sexual behavior (also designated “sleepsex,” “sexsomnia,” and “atypical sexual behaviors in sleep”). Most published cases involve young men with histories of sleepwalking and sleep terrors. Pharmacotherapy (eg, bedtime off-label use of clonazepam) is typically reserved for recalcitrant patients.

Substance-/medication- induced sleep disorder

Parasomnias resembling disorders of arousal can be related to the use of many psychotropic drugs, in particular sedative-hypnotics. Sleepwalking and other amnestic complex sleep-related behaviors have been reported among psychiatric patients taking benzodiazepines. Behaviors can be prolonged and include amnestic nocturnal eating, sexual activity, and even sleep driving. In particular, the hypnotics with short duration of action seem to be associated with these phenomena, whereas longer-duration benzodiazepines tend to suppress them. It is likely that the drugs dull the transition between sleep and wakefulness, permitting behavior unconstrained by executive function in susceptible individuals.

Other drugs associated with sleepwalking and sleep terrors include neuroleptics, such as olanzapine and quetiapine; antidepressants, such as paroxetine, reboxetine, and bupropion; mood stabilizers and antiepileptics, such as lithium, topiramate, and valproic acid combined with zolpidem; stimulants; antihistamines, often in various combinations; metoprolol; and fluoroquinolone.

An interesting subset of this category is sleepwalking with sleep- related eating disorder triggered by sedating agents in the presence of restless legs syndrome, which may be a predisposing factor. The most common offending medications include benzodiazepines-zolpidem in particular. Restless legs syndrome may also occasionally present in patients who are taking TCAs, anticholinergics, lithium, triazolam, olanzapine, or risperidone.

Here's an update on parasomnias-the undesirable physical, experiential, or behavioral phenomena that occur exclusively during sleep onset, during sleep, or during arousals from sleep.

Sleep Deprivation