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Delayed sleep wake phase disorder (DSWPD) is a circadian rhythm sleep disorder characterized by a mismatch between a person’s internal biological clock (or circadian rhythm) and societal norms. As a result of attempting to sleep out of sync with the internal biological clock, individuals with DSWPD report a significantly prolonged sleep onset, difficulties waking in the morning, suboptimal sleep duration, and excessive daytime sleepiness. If the preferred schedule is allowed (eg, the individual goes to bed late and sleeps late into the morning), sleep duration and maintenance are normal.

Onset of DSWPD often occurs during adolescence as a result of behavioral and physiological factors. Prevalence estimates of DSWPD in adolescents vary; however, ranges from 3.3% to 16% have been reported.

Presenting symptoms of DSWPD often mimic those of other sleep disorders, including insomnia or hypersomnia. Polysomnography is not indicated unless symptoms of other sleep disorders are present. Suggested strategies for assessment of DSWPD are provided in 

Assessment of sleep patterns including bedtime routines, bedtimes, sleep-onset latency, wake times, and sleep environment are critical to an effective differential diagnosis. Differentiating the features from insomnia entails understanding the adolescent’s schedule during school compared with weekends or holidays. Individuals with DSWPD often report normal sleep-onset latency and sleep duration on weekends, holidays, or school vacations when they are allowed to sleep on their preferred schedule. In contrast, those with insomnia will report lengthy sleep-onset latency regardless of the time they go to bed. In addition, those with insomnia may report difficulties with sleep maintenance-a feature not as characteristic of DSWPD.

Sleep hygiene is also an important area of assessment. Adolescents with DSWPD may develop compensatory behaviors to manage frustrations related to lengthy sleep-onset latency. Such behaviors often function to alleviate frustration at sleep onset (eg, phone use) or compensate for daytime sleepiness (eg, napping). However, restriction of the sleep-inhibiting behaviors as a stand-alone treatment rarely helps decrease sleep-onset latency in DSWPD.

Because assessment and management of circadian rhythm disorders rely on granular information on night-to-night sleep patterns, sleep logs are typically recommended. Differentiating schedules and sleep-onset latency between school days and weekends can provide evidence toward a delayed sleep phase relative to insomnia. The adolescent should be coached on maintaining the sleep logs for approximately 2 weeks, as parents often have limited information on their teen’s sleep patterns.

Actigraphy entails the use of a portable device, worn on the non-dominant wrist over a period of time to track movement. It is commonly used in research and in clinical practice. Actigraphy can be invaluable in both the assessment of DSWPD and the evaluation of intervention. In clinical practice, actigraphy can be difficult to obtain outside of a sleep setting, and interpretation of data requires some expertise. Commercial devices (eg, FitBit) are less reliable than actigraphy and typically should not be used as a substitute.

Management strategies include use of timed sleep schedules, melatonin, bright light therapy, and chronotherapy. There is insufficient evidence to recommend use of hypnotics at sleep onset or use of stimulants to promote wakefulness. This is in contrast to what is customary in many medical practices. A summary of treatment options can be found in 

Comprising 2 phases-the active phase and the maintenance phase-chronotherapy is an intensive intervention that helps reset the internal clock. The active phase involves a sequential delay of bed and wake times by 2 to 3 hours daily until a desired sleep schedule is achieved. After the active phase of treatment, a strict sleep schedule must be maintained making this treatment challenging to implement. From a clinical perspective, the benefits of the intervention include quickly shifting the schedule, which can be critical if the patient is frequently absent or late for school.

Kate, a 14-year-old, presents to the pediatric sleep clinic because of difficulties with sleep onset. At baseline, she describes sleep-onset latency of 3 to 5 hours with a bedtime of 10 pm, with several nocturnal arousals. On school days, because of the bus schedule, she wakes up between 5 and 6 am. She reports significant fatigue, especially during her morning classes.

On weekends, Kate goes to bed at 2 am; consequently, sleep-onset latency is shorter and she is able to sleep until 9 am. She reports increased energy on weekends when she sleeps on her preferred schedule.

Sleep-inhibiting activities at sleep onset include use of her phone and computer in bed. She also spends significant time in bed not sleeping as a means to escape from negative interactions with her parents and because she prefers to do her homework in her room.

During the initial evaluation, there are no concerns related to sleep-disordered breathing, narcolepsy, or parasomnias.

Kate describes her sleep as a mild problem, although she notes it can negatively affect her mood. She states that she is about to enter high school and plans on being heavily involved in athletics and other extracurricular activities. She believes that her sleep problems would limit her ability to engage in such activities.

Kate’s parents described her sleep concerns as within the moderate range. They describe significant difficulties helping her wake up in the morning, which leads to increased tension that persists throughout the day. In addition, her parents express significant frustration with Kate’s afternoon naps-they feel the naps exacerbate her sleep problems.

Given Kate’s decreased sleep-onset latency and improved sleep maintenance when allowed to have her preferred sleep schedule, the initial assessment indicates a need for more information related to DSWPD. It is recommended that Kate maintain sleep logs for 2 weeks.

At the second visit, the sleep logs support a diagnosis of DSWPD. Kate and her parents are provided with information on DSWPD to diffuse the tension surrounding Kate’s sleep patterns. When discussing treatment options, the family expresses a preference not to use melatonin because of frustrations related to past use. In addition, her parents do not think it is feasible for Kate to wake up earlier to use bright light therapy. Given the significant delay in sleep onset as well as the need to quickly adjust her bedtime to help Kate remain in school, chronotherapy is the best option.

The active phase of therapy means that the bedtime/wake time moves “around the clock” for 6 to 8 days. Keeping the sleep time to less than the recommended 9 hours for adolescents is used to increase sleep drive. Chronotherapy begins with a 3 am bedtime on day 1. This time is selected in the hope of decreasing sleep-onset latency. Subsequent days are outlined with the family, and a chronotherapy schedule is provided (

At the conclusion of the active phase, Kate’s progress is reviewed during the third visit. She reports that she is able to be adherent throughout the week and is maintaining a regular bed and wake time, but she continues to be fatigued upon waking. Emphasis is placed on maintaining the same bed and wake times regardless of whether it is a school day or a weekend (maintenance phase). Problem-solving occurs during this visit to account for special activities (eg, prom, sleepovers). The maintenance phase lasts about 2 months. During this time, it is critical to keep to the same bedtimes and wake times to “set” the internal clock. The recommended sleep time for Kate is 10 pm to 5:30 am.

A final visit is scheduled 2 months later to assess the maintenance phase. Kate reports that her weekend activities help her maintain the sleep schedule because they promote early waking. She no longer naps and falls asleep within 30 minutes of bedtime, and she is able to sleep for 7.5 hours a night. Given the maintenance of gains, visits are moved to an as-needed basis.

Kate is a relatively straightforward patient with no comorbid psychiatric or medical diagnoses. Modifications would need to be made in the case of psychiatric diagnoses in which the patient should not be unsupervised for long periods (eg, depression with suicidal ideation, substance abuse). In these situations, we have had parents go through the active phase of chronotherapy with their child to provide monitoring and support. Sleep deprivation can also exacerbate depression, and close monitoring is needed with such patients.

DSWPD is a circadian sleep disorder commonly seen in adolescents. Thorough and careful assessment is critical to differentiating features of DSWPD from other common sleep problems. DSWPD can affect the patient’s mood and result in chronic sleep deprivation. Several options exist to help manage DSWPD-all of which require close follow-up because relapse is common.

Dr. Dore-Stites is Clinical Assistant Professor of Pediatrics and Communicable Diseases, Michigan Medicine, University of Michigan, Ann Arbor, MI; Dr. Conroy is Clinical Associate Professor of Psychiatry and Clinical Director of the Behavioral Sleep Medicine Program, Michigan Medicine, University of Michigan Hospital, Ann Arbor.

The authors report no conflicts of interest concerning the subject matter of this article.

 Sivertsen B, Pallesen S, Stormark K, et al. Delayed sleep phase syndrome in adolescents: prevalence and correlates in a large population based study. 

 Saxvig I, Pallesen S, Wilhelmsen-Langeland A, et al. Prevalence and correlates of delayed sleep phase in high school students. 

 Bartlett D, Biggs S, Armstrong S. Circadian rhythm disorders among adolescents: assessment and treatment options. 

 Auger RR, Burgess HJ, Emens JS, et al. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24 hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-W. 

Here: suggested strategies for assessment and management of this circadian sleep disorder commonly seen in adolescents.

Delayed Sleep Wake Phase Disorder in Adolescents: Chronotherapy and Best Practices

Is your patient concerned about daylight savings time? This handout offers tips for getting a good night's sleep.

Train yourself to be awake and sleepy at regular times

• Stick to approximately the same times to wake up and to go to bed. Don’t vary this schedule much on weekends

• Wake up at a fixed time every day-regardless of how long you slept during the night. This is hard to do but will be really helpful by making you sleep better and better over the next few days

• Rest as much as you need to during the day, but do not lie down or nap. Otherwise, your sleep cycle will be worse

• Close the blinds; wear earplugs if necessary

• Sleep in a cool but not cold bedroom. A temperature of about 65°F is ideal for most people

• If you cannot sleep, get up and go into another room

• Only get into bed when you are sleepy

• Stay away from caffeine after about 3 pm

• Establish a bedtime “ritual” that you follow every evening. This may include a warm bath or shower, some light reading, or listening to soothing music

• Avoid alcohol. It may help you to fall asleep, but you will probably have a restless night

," by Rajnish Mago, MD, on which this Tipsheet was based.

This article was originally posted on February 12, 2012 and has since been updated.

Concerned about daylight savings time? This patient handout offers tips for getting a good night's sleep. 

Sleep Hygiene: Tips on Getting a Restful Night's Sleep

Healthy sleep is required for restoring functioning and vitality, promoting memory consolidation, and maintaining immune function. However, many individuals are affected with sleep disorders. There are about 

 who have problems with sleep, with associated costs of about $16 billion each year in medical care. Insomnia affects about 10% to 15% of the population, sleep apnea affects about 10%, followed by other sleep disorders, such as restless legs syndrome and circadian rhythm disorders. Untreated sleep disorders can increase the risk of heart disease, motor vehicle accidents, memory problems, depression, and impaired functioning.

The DSM-5 Sleep-Wake Disorders Work Group worked closely with other nosology systems (eg, International Classification of Sleep Disorders, third edition [ICSD-3]) to incorporate changes in diagnoses. DSM-5 sleep-wake disorders are now more in sync with other medical disorders and sleep disorders classificatory systems. In DSM-5, the pathological and etiological factors associated with sleep-wake disorders are taken into consideration, as is the increase in awareness and knowledge gained from sleep studies. The aim is to increase uniformity and consistency among health care professionals when they are assessing and treating patients with various sleep disorders. Sleep-wake disorders comprise 11 diagnostic groups:

• Circadian rhythm sleep-wake disorders

• Non–rapid eye movement (NREM) sleep arousal disorders

• Rapid eye movement (REM) sleep behavior disorder

• Restless legs syndrome and substance-/medication-induced sleep disorder

Growing evidence has shown that sleep disorders coexist with other medical and psychiatric disorders and may not be mutually exacerbating. DSM-5 underscores the need for independent clinical attention of a sleep disorder regardless of mental or other medical problems that may be present. DSM-5 also recognizes that coexisting medical conditions, mental disorders, and sleep disorders are interactive and bidirectional. Two previous diagnoses have been eliminated: sleep disorder related to another mental disorder and sleep disorder related to another medical condition.

The most significant change in sleep-wake diagnostic criteria is in the insomnia classification (

). The DSM-IV distinction into primary and secondary insomnia is removed in DSM-5. This stresses the comorbid nature of insomnia and calls for treatment of both insomnia and the medical disorder. This change in insomnia diagnostic criteria in ICSD-3 and DSM-5 implies a paradigm shift.

Insomnia is insomnia is insomnia, according to Michael Sateia,

. Insomnia is a disorder in itself that needs independent clinical attention. The diagnostic criteria have been made more specific by putting in frequency criteria; in addition, the duration has been changed to 3 months. DSM-5 and ICSD-3 insomnia diagnostic criteria are similar because of collaborative efforts between the American Psychiatric Association and the American Association of Sleep Medicine classification task forces. The changes in insomnia diagnostic criteria give it more specificity and ensure greater uniformity. According to Charles Reynolds III, MD, chair of the 

, “To achieve optimal treatment outcomes in people with both a psychiatric disorder and insomnia, the clinician needs to target both disorders.”

Mr S, a 53-year-old man, is referred to a sleep disorders clinic for evaluation of insomnia and daytime somnolence. He has been struggling with depression and anxiety, for which he is being treated.

Mr S reports that he has had insomnia for many years and that it had gotten worse in the past 10 years. He has trouble with sleep initiation-it often takes him more than an hour to get to sleep. Once he is asleep, he wakes up multiple times then struggles to get back to sleep. He tosses and turns in bed until morning and gets up feeling tired and exhausted.

His primary care physician prescribed zolpidem, but this caused sleepwalking episodes, so Mr S discontinued it. Mirtazapine was tried, but it caused weight gain and was also discontinued. He takes trazodone for insomnia and fluoxetine for depression. This combination has been helpful, but he still has persistent symptoms of insomnia and depression. His wife reports that he snores and there have been occasions when he stopped breathing while sleeping. He has comorbid type 2 diabetes mellitus, hypertension, and gastroesophageal reflux disease.

The primary diagnosis is DSM-5 insomnia disorder. Given the comorbid symptoms of depression and obstructive sleep apnea, it would be difficult to evaluate whether Mr S has DSM-IV primary insomnia; DSM-5 allows the clinician to make a causal attribution between insomnia and comorbid depression and obstructive sleep disorder.

Comorbid obstructive sleep apnea is diagnosed on the basis of clinical and polysomnographic evaluations. Mr S is treated with continuous positive airway pressure. He reports improvement in his energy level during daytime, but he continues to struggle with insomnia. His nighttime awakenings decreased to 2 or 3 times and nocturia is diminished as well. Despite these improvements, he still struggles with insomnia. An increase in the dose of trazodone by 75 mg and initiation of cognitive-behavioral therapy for insomnia (CBT-I) helped him significantly. Mr S is sleeping bet- ter and continues CBT-I; treatment with trazodone continues, with a slow and gradual taper.

The distinction of primary hypersomnia has been eliminated and replaced with hypersomnolence disorder. The added criterion of coexisting mental and medical disorders that do not adequately explain the predominant complaint of hypersomnolence emphasizes the need for independent clinical relevance and attention to the disorder. In addition, there are duration criteria-acute (less than 1 month), subacute (1 to 3 months), and chronic (longer than 3 months)-and there is the dimensional approach of specifying the severity of the disorder as mild, moderate, or severe.

DSM-5 incorporates current advancements in our understanding of 

 by incorporating hypocretin deficiency into its diagnostic criteria. The criteria of irrepressible sleepiness occurrence is now at least 3 times per week over the past 3 months (previously specified as daily). Polysomnographic and multiple sleep latency findings are also incorporated into the diagnostic criteria, which gives the diagnosis more specificity and uniformity and makes it more objective.

There are now 5 subtypes of narcolepsy with mild, moderate, or severe specificity:

• Narcolepsy without cataplexy but with hypocretin deficiency

• Narcolepsy with cataplexy but without hypocretin deficiency

• Autosomal dominant cerebellar ataxia, deafness, and narcolepsy

• Autosomal dominant narcolepsy, obesity, and type 2 diabetes mellitus

• Narcolepsy secondary to another medical disorder

In DSM-5, breathing-related sleep disorders are divided into 3 relatively distinct disorders:

This change uses the pathophysiologic basis of these disorders. DSM-5 includes diagnoses of obstructive sleep apnea on polysomnography alone when there are more than 15 respiratory events an hour, regardless of symptoms. This criterion highlights the importance of diagnosing and treating obstructive sleep apnea, which is believed to cause and worsen medical disorders such as hypertension, diabetes, obesity, coronary artery disease, congestive heart failure, cardiac arrhythmias, substance use, and anxiety.

The subtypes of circadian rhythm sleep-wake disorders have been changed and expanded to include advanced sleep-phase type, irregular sleep-wake type, and non–24-hour sleep-wake type. The jet lag type has been removed. Delayed sleep-phase type is now sub-specified into familial type and overlaps with non– 24-hour sleep-wake type. And, it incorporates familial sub-specification of advanced sleep-phase type disorder. Circadian rhythm sleep-wake disorders are sub-specified into episodic, persistent, or recurrent.

Parasomnias are disorders characterized by abnormal behavioral, experiential, or physiological events that occur during sleep, specific sleep stages, or sleep-wake transitions. DSM-5 divides NREM sleep arousal disorders into sleepwalking type and sleep terror type. It further sub-specifies sleepwalking type with sleep-related eating or sleep-related sexual behavior (sexsomnia).

The criteria for nightmare disorder includes coexisting mental and medical disorders that do not adequately explain the predominant complaint of dysphoric dreams. The specificity criteria include duration and severity indicators.

DSM-5 gives specific diagnostic criteria for REM sleep behavior disorder as a parasomnia category of its own rather than including it as a subtype of parasomnia not otherwise specified (NOS) as in DSM-IV. Parasomnia NOS has been removed in DSM-5.

 is elevated to its own diagnostic and independent category to incorporate the frequency and duration of symptoms and specific symptom criteria. This is more in line with the ICSD classification of restless legs syndrome.

Substance-/medication- induced sleep disorder

DSM-5 broadens substance-induced sleep disorder of DSM-IV to incorporate medication-induced sleep disorder. It has been evident from clinical experience and literature that many medications, particularly psychotropic medications, can cause or exacerbate sleep problems and disorders. Adding this category broadens clinical acumen and calls for clinicians to evaluate for possible medication-related effects.

Evaluation and treatment of sleep disorders are of paramount importance in health promotion and prevention of disease, morbidity, and mortality. DSM-5 strives to bring uniformity and more precision in diagnoses of sleep disorders-sleep-wake disorders are now more in sync with other medical disorders and sleep disorders classificatory systems. DSM-5 stresses the need for independent clinical attention to sleep disorders regardless of psychiatric or other medical problems that may be present.

The changes in DSM-5 will hopefully lead to better uniformity and precision in diagnoses and consequently better clinical attention to and treatment of sleep disorders. The changes in the diagnostic criteria for insomnia disorder are particularly important and will have significant implications in diagnoses, treatment, and research.

Dr Khurshid is Clinical Associate Professor and Chief of the Neuromodulation and Sleep Disorders Program in the department of psychiatry at the University of Florida College of Medicine in Gainesville. He reports no conflicts of interest concerning the subject matter of this article.

 Ohayon MM. Prevalence and comorbidity of sleep disorders in general population [in French]. 

 Daley M, Morin CM, LeBlanc M, et al. The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers. 

 Chung WS, Lin CL, Chen YF, et al. Sleep disorders and increased risk of subsequent acute coronary syndrome in individuals without sleep apnea: a nationwide population-based cohort study. 

 Sateia MJ. International Classification of Sleep Disorders-third edition: highlights and modifications. 

 Lamberg L. Manual updates sleep disorders diagnoses. 

http://psychnews.psychiatryonline.org/doi/full/10.1176/appi.pn.2014.8b20

DSM-5 sleep-wake disorders are now more in sync with other medical disorders and sleep disorders classificatory systems. Here's what's changed. 

A Review of Changes in DSM-5 Sleep-Wake Disorders

Insomnia is no longer considered an innocuous malady. We are beginning to discover that insomnia does have a number of impairments associated with it. Many of these are cognitive in nature (eg, difficulty processing and thinking). It can affect personal relationships and produce daytime fatigue.

Issues beyond cognition include the development of metabolic syndrome, diabetes, and hypertension; a lack of sleep can even influence long-term survival and morbidity.

In this video, Dr Karl Doghramji discusses key points of a presentation he gave at  PsychCongress. Dr Doghramji is Professor of Psychiatry, Neurology, and  Medicine, and Medical Director of the Jefferson Sleep Disorders Center  at Thomas Jefferson University in Philadelphia.  

Insomnia-a sleep disorder that can pose impairments far more debilitating than than problems with cognition (eg, difficulty processing, unclear thinking).

What’s New Under the Moon-Insomnia and Sleep Deprivation

With increasing knowledge about sleep and its disorders and widespread use of diagnostic testing for sleep, more patients with sleep-disordered breathing (SDB) are being identified. Various comorbid medical, neurological, and psychiatric disorders are more prevalent in patients with clinically significant SDB. This article explores the relationship between SDB and psychiatric disorders and its implication for practicing psychiatrists.

Alex is a 58-year-old married, certified public accountant who snores loudly and has frequent nocturnal awakenings, sometimes with gasping or choking. He generally goes to bed at midnight and wakes up at 6:30 am. On weekends, he usually sleeps 1 or 2 hours longer and sometimes takes a 1-hour nap.

He gained 12 lb in the past year but is not obese (his BMI is 28.5). He reports increasing back pain, fatigue, irritability, and cognitive problems. He occasionally feels anxious and moody, especially when his aches and pains are exacerbated. Six months ago, nocturia developed, but prostate-specific antigen (PSA) test results were normal. At that time, he also began having morning dry mouth, morning headaches, sadness, tiredness, and generally depressed mood. Treatment with an SSRI was initiated; he also had a brief trial with methylphenidate.

He was referred for polysomnography, which revealed severe obstructive sleep apnea with significant oxyhemoglobin desaturations occurring during REM sleep. There were also some central-type SDB events. The patient was treated with bilevel positive airway pressure, with good effect.

This case illustrates a fairly common story. When a middle-aged man becomes less active, works at a sedentary job, gains weight, and begins to snore, chances are that he has or is developing SDB. Job demands and family responsibilities promote sleep schedule restriction, often prompting increased caffeine intake. Nonetheless, sleepiness, tiredness, and fatigue almost invariably follow. Obvious signs include fatigue, attention problems, less effective coping, and depressed mood. A patient may recognize cognitive dulling, as in this case.

Less obvious symptoms include nocturia, morning headache, and difficult to control pain. Our training dictates that we immediately suspect prostate disease when nocturia develops. However, the negative intrathoracic pressure created by attempting to inhale against an occluded airway provokes release of atrial natriuretic peptide, especially during REM sleep. The resulting nocturia is often periodic, occurring at 1- to 2-hour intervals, with minimal voiding; PSA test results are normal.

The negative intrathoracic pressure also creates afterload on the heart and may be associated with increased levels of inflammatory cytokines. Morning headaches can be provoked by hypoxemia during REM-related SDB. REM sleep episodes become progressively longer during the sleep period, and obstructive SDB is usually more severe during REM sleep. In patients who smoke cigarettes or who have a history of smoking, lung function declines more quickly as a function of age. In patients with SDB, severe hypoxemia can result. Sleep loss and pain coexist in a vicious circle: sleep loss lowers pain threshold and pain disrupts sleep. Sedative hypnotics to promote sleep and opioid analgesics reduce respiratory drive, raise arousal threshold, and generally worsen SDB. The net result is greater sleep disruptions and continued pain.

 
Clinical spectrum of sleep-disordered breathing
 

SDB includes a wide spectrum of disorders that manifest as compromised breathing during sleep (

). At one end of the spectrum is primary snoring, ie, snoring without any daytime symptoms or clinically significant reduction in the inspiratory flow. At the other extreme is obstructive sleep apnea, a serious, chronic, and sometimes debilitating condition. SDB also includes cen-tral sleep apnea and sleep-related hypoventilation.

What is already known about sleep-disordered breathing (SDB) and the correlation with psychiatry? 
? Psychiatric medical conditions, particularly depression and anxiety, are common in patients with SDB. Multiple mechanisms are proposed to explain this relationship.

What new information does this article provide? 
? Sleepiness and impaired coping mechanisms link SDB, depression, and anxiety disorders. More proactive case findings and SDB treatment in patients with depression and anxiety may help improve management of the psychiatric condition. However, some psychiatric medications can adversely affect sleep and breathing.

What are the implications for psychiatric practice? 
? SDB signs and symptoms overlap with mood, anxiety, and other psychiatric illnesses. In some cases, they may masquerade as these disorders, but SDB can also provoke and/or exacerbate other psychiatric conditions. In addition to obvious symptoms in at-risk populations, SDB should be considered in menopausal women in whom insomnia and fatigue have recently developed and in children who snore and have attention problems. Some screening tools and evaluation techniques in psychiatric practices may help identify the SDB at-risk population.

Obstructive types of the sleep-related breathing disorders involve narrowing and flow limitation in the upper airway. During inhalation, this can lead to collapse (apnea), partial collapse (hypopnea), or increased resistance. As airway resistance increases, the effort to breathe and the work of breathing increase. If the effort to breathe increases past some threshold or if the airway collapses, a CNS arousal ultimately occurs, returning ventilation to voluntary control so that the airway can be dilated and breathing can resume. This process is often accompanied by cascading snores, possibly followed by a period of silence (that may persist for several seconds to more than 1 minute), and finally an explosive breath (with possible snorting, gasping, and/or coughing). The patient may quickly fall back to sleep and resume snoring, possibly repeating this sequence hundreds of times during the night.

 
Risk factors, symptoms, and clinical features of sleep-disordered breathing
 

 lists risk factors, common symptoms, and clinical features of SDB. Many consequences of SDB are also common psychosomatic symptoms. In this case, however, the etiology is well documented and the problem diminishes or disappears when the sleep-disordered breathing is treated.

Various questionnaires are available to help identify persons at high risk for SDB. One such questionnaire is the STOP BANG questionnaire that can be used in clinical practice.

Positive airway pressure (PAP) therapy is the first-line treatment for most patients with obstructive sleep apnea. The most common is continuous PAP, which provides a constant airflow that is used to “pneumatically splint” the vulnerable portions of the nasopharyngeal airway by having air blown into the patient’s nose and/or mouth using a nasal or full face mask, nasal pillows, or nasal prongs. Bilevel PAP provides 2 pressure levels-one during inhalation and a lower one during exhalation. The pressure drop during exhalation increases comfort for patients who have difficulty in exhaling against the incoming airflow. The automatic self-adjusting PAP uses computer-controlled flow variations to determine and supply optimal pressure. Finally, noninvasive positive pressure ventilation devices provide ventilatory assist. These devices are similar to bilevel PAP; however, the rate of oscillation between the two pressures is specified.

Overall, continuous PAP is extremely safe and very effective in patients with SDB, and its benefits are well sustained. Patients who received continuous PAP and conservative therapy (sleep hygiene and weight loss) had decreased sleepiness and improved quality of life compared with patients who received only conservative therapy.

 Similarly, in a randomized, double-blind, placebo-controlled study, patients who received therapeutic continuous PAP had less sleepiness and better quality of life than patients who received subtherapeutic continuous PAP.

 However, negative study results have also been reported.

 
Psychiatric comorbidities in patients with obstructive sleep apnea compared with patients without obstructive sleep apnea
 

Studies show a higher prevalence of psychiatric conditions in patients with SDB. Using Department of Veterans Affairs administrative databases, we compared patients with and without SDB. A high prevalence of psychiatric comorbid conditions was seen in more than 100,000 patients with this diagnosis (

). Similar results have been found in non-veteran populations.

. Depressive symptoms are frequently reported in patients with obstructive sleep apnea. However, the association between depression and obstructive sleep apnea remains controversial. Findings from our study as well as those from others indicate a higher prevalence of depressive symptoms in patients who have obstructive sleep apnea.

In contrast, other studies cast doubt on such a relationship.

Although causality cannot be discerned from these studies, intervention studies provide important clues. Means and colleagues

 showed that treatment of obstructive sleep apnea with continuous PAP reduced the depressive symptoms. Continuous PAP reduced depression scores in patients with major depression and obstructive sleep apnea who were already receiving optimal antidepressive pharmacotherapy.

 Furthermore, a systematic review of randomized trials of continuous PAP and obstructive sleep apnea showed improved mood following therapy.

The mechanism(s) underlying the connection between SDB and psychiatric symptoms is a matter of debate. From a psychiatric perspective, one can conceptualize the relationship as stemming from a direct physiological consequence of the general medical condition (in this case, sleep deprivation and nocturnal hypoxia/hypercapnia). Therefore, the increased prevalence of depression with SDB would not be surprising given that such a relationship is seen in other diseases that produce hypoxia and impair quality of life (eg, chronic obstructive pulmonary disease).

 On the other hand, excessive sleepiness and fatigue as a result of sleep apnea produce significant social and personal problems and result in depression.

 showed that the daytime sleepiness is a strong predictor of depressive symptoms in patients with SDB.

Sleep apnea and depression can be bridged conceptually by vital exhaustion. Vital exhaustion refers to a state characterized by elevated somatic and cognitive symptoms of depression without affective symptoms. Our group as well as others demonstrated that vital exhaustion profiles were affected in patients with SDB.

 Therefore, depressive manifestations in patients with sleep apnea may reflect the patients’ vital exhaustion, which differs dramatically from melancholic affective mood changes observed in more typical forms of depression and dysthymia. As such, depressive phenomena in patients who have sleep apnea should be more akin to depression secondary to chronic medical illness.

. An association between obstructive sleep apnea and anxiety has also been seen. Our data reveal a higher prevalence of clinically diagnosed anxiety associated with SDB.

 found higher anxiety scores in patients with SDB than in controls (measured by the General Severity Index).

Many years ago, researchers began discussing a link between PTSD and REM sleep behavior disorder (RBD).

 Under normal circumstances, the hypopolarization of alpha and gamma motor neurons during REM sleep maintains a func-tional paralysis that prevents the sleeper from enacting his or her dream content. In RBD, the mechanisms that produce REM-related atonia fail and fictive movements become real actions, sometimes resulting in serious injury. Combat veterans with PTSD seem especially vulnerable to REM atonia failure, and dream-enactment reports are more common than in the general population.

More recent findings reveal possible parasomnias involving sleep-related behaviors triggered by SDB-in particular, sleepwalking, night terrors, RBD, and sleep-related eating disorder. Further complicating the matter is that sedative/hypnotics can provoke both SDB events and these behavioral parasomnias. Ongoing studies are attempting to untangle these interwoven factors.

Perhaps most intriguing is that SDB events may provoke nightmares, RBD, and sleepwalking episodes. It stands to reason that any choking episode can initially produced intense fear, anxiety, and/or panic. Pagel and Kwiatkowski

 studied nightmares in 400 patients who were also evaluated polysomnographically for SDB. Patients with severe SDB had fewer recalled nightmares than those with milder disease (30% vs 70%, respectively). This may be because patients with severe SDB have reduced REM sleep, are less likely to fully awaken, or have habituated to the awaken-ings with choking and gasping. It would be interesting to see whether this relationship reverses in patients with PTSD, given that severe SDB is associated with increased norepinepherine turnover due to sympathetic nervous system up-regulation in response sleep disturbance.

Sleep problems (and especially nightmares) are cardinal symptoms of PTSD. Our data strongly support an association between SDB and PTSD.

 This association has also been reported by others.

 posit an arousal-based mechanism initiated by posttraumatic stress–promoting SDB development in trauma survivors. Of note: continuous PAP treatment of obstructive sleep apnea improved insomnia, nightmares, and PTSD symptoms, which may indicate that causality is bi-directional.

Sleep loss or disturbance, whether associated with SDB or other conditions, can impair an individual’s coping mechanisms. When sleepy, we are easily frustrated and must make more effort to perform otherwise mindless and rote tasks. In patients who already have difficulty in functioning, especially those prone to impatience, anger, panic, and/or denial, the additional stressor of impaired sleep can exceed the capacity of their defense mechanisms. Thus, SDB can create a special vulnerability to psychological problems-especially anxiety.

. Recent studies suggest a relationship between SDB and ADHD in pediatric patients. Findings suggest that many children and adolescents (25% to 50%) with ADHD have sleep problems.

 In attention and hyperactivity among general pediatric patients have been shown to be associated with increased daytime sleepiness, snoring, and other symptoms of SDB.

 found a high incidence (20% to 30%) of obstructive sleep apnea in patients with full ADHD syndrome; once obstructive sleep apnea was treated, improvements in behavior, inattention, and overall ADHD were seen. Naseem and colleagues

 reported on 3 patients with adult hyperactivity; all 3 patients suffered from symptoms of obstructive sleep apnea. With continuous PAP, 2 of the 3 patients showed improvement in their sleep and hyperactivity symptoms.

The vast majority of patients with SDB report sleepiness. If the sleepiness level exceeds the individual’s compensatory alertness mechanisms, he may resort to additional strategies to maintain focus (eg, caffeine ingestion). Arousal and attention are fundamental to most cognitive tasks, particularly those that require quick or well-timed responses.

 However, beyond simple attentiveness, diminished executive task abilities (sometimes considered frontal lobe functions) were correlated with sleepiness and, thus by association, with SDB.

SDB is adversely affected by most sedating medications. Exacerbation of SDB is not restricted to barbiturates, benzodiazepines, and other sleeping pills. Any sedating drug-antidepressant, antipsychotic, analgesic, or antihistamine-can adversely affect breathing during sleep. While these compounds reduce respiratory drive (eg, opioid analgesics), more importantly, they can raise arousal threshold (eg, sedative/hypnotics). If an airway obstruction occurs, ventilation is resumed in response to CNS arousal that allows voluntary dilation of the airway. The more sedated the individual, the more difficult it is to awaken him and the longer it takes to open the airway. Some substances also exacerbate preexisting SDB by compromising muscles responsible for maintaining upper airway patency (eg, benzodiazepines) or allowing the base of the tongue to occlude the airway (eg, alcohol).

Insomnia is a common symptom in many psychiatric disorders and may act synergistically in that sleep loss worsens the overall condition. As such, treatment of insomnia can be critical to managing the psychiatric condition. If the insomnia worsens or if the patient continues having nonrefreshing sleep after a sedative/hypnotic is administered and the duration of sleep is adequate, consider possible SDB. This is especially important if the patient snores, is obese, reports fatigue, or has hypertension. If suspicion is high, a polysomnographic sleep evaluation is indicated.

Psychiatric comorbid conditions, especially mood disorders and anxiety disorders, are common in patients with SDB. A thorough sleep evaluation is warranted in patients with psychiatric conditions that have SDB risk factors. Screening questionnaires, such as STOP BANG, may help identify persons at risk for SDB. These include middle-aged (or older) postmenopausal women in whom insomnia or snoring has developed, patients who are obese, and patients whose sleep problems worsen when they are taking sedative/hypnotics. An SDB diagnosis, appropriate therapy, and follow-up in these patients may improve management of their comorbid psychiatric conditions.

 Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. 2008.

 http://sleepmed.com.au/STOP_questionaire.pdf

Ballester E, Badia JR, HernÃ¡ndez L, et al. Evidence of the effectiveness of continuous positive airway pressure in the treatment of sleep apnea/hypopnea syndrome [published correction appears in 

Sleep-disordered breathing is common in patients with mood and anxiety disorders. This article explores the implication for practicing psychiatrists whose patients have sleep disorders.

The Correlation Between Sleep-Disordered Breathing and Psychiatry

Melatonin was first isolated from the bovine pineal gland in 1958.

 In humans, it is the main hormone synthesized and secreted by the pineal gland. It is produced from a pathway that includes both tryptophan and serotonin. Melatonin displays high lipid and water solubility, which allows it to diffuse easily through most cell membranes, including the blood-brain barrier. Its half-life is about 30 minutes, and it is cleared mostly through the liver and subsequently excreted in the urine as urinary 6-sulfatoxymelatonin.

In humans and most diurnal mammals, melatonin is secreted at night with a robust circadian rhythm and maximum plasma levels that occur around 3 to 4 AM. The daily rise of melatonin secretion correlates with a subsequent increase in sleep propensity about 2 hours before the person’s regular bedtime. The time before this secretion is the least likely for sleep to occur, and when it starts, the propensity for sleep increases greatly as the “sleep gate” opens. The rhythmic release of melatonin is regulated by the central circadian rhythm generator-the suprachiasmatic nucleus (SCN) of the anterior hypothalamus.

Most of the chronobiotic and hypnotic effects of melatonin are mediated through 2 receptors: MT1 and MT2. Both subtypes have high density in the SCN, but they are also spread throughout other sites in the brain and other organs, which indicates that melatonin likely affects other biological systems. Given this distribution, it is not surprising that melatonin appears to have a number of effects on human biology that have not been fully elucidated, including regulating the sleep-wake cycle and acting as a neurogenic/neuroprotective agent.

It appears that the function of melatonin is to mediate dark signals and provide night information, a “hormone of darkness,” rather than be the hormone of sleep. It has also been thought to be an “endogenous synchronizer” that stabilizes and reinforces various circadian rhythms in the body.

 Although direct hypnotic effects have been seen, melatonin’s effect on sleep appears more involved in the circadian rhythm of sleep-wake regulation. The phase shifting effects of melatonin appear to be due to the MT2 receptor, while the MT1 receptor is more related to sleep onset.

Melatonin and the circadian rhythm of the sleep-wake cycle

The daily sleep-wake cycle is influenced by 2 factors: process C (circadian), an endogenous “clock” that drives the rhythm of the sleep-wake cycle; and process S (sleep), a homeostatic “sleep propensity” that determines the recent amount of sleep and wakefulness accumulated. The SCN interacts with both processes, and it is where the main component of process C is located. Excitatory signals from the SCN and subsequent melatonin suppression are thought to promote wakefulness during the day in response to light and the suppression of melatonin inhibition of the SCN. This inhibition is released in the dark phase and leads to melatonin synthesis/release with consequent sleep promotion.

The sleep-wake cycle is only one of many circadian rhythms. Left without stimulus, the circadian period of sleep/wake is around 24.2 hours, but this can vary from 23.8 to 27.1 hours. This period is inherited and is closely related to intrinsic circadian preference for nighttime (long period) or daytime (short period), which can be determined by measuring the timing of maximal secretion of melatonin and subsequent related core body temperature (CBT). Maximum sleepiness occurs when CBT is at its lowest and melatonin levels are at their highest.

Many exogenous and endogenous factors (called zeitgebers) can shift a circadian rhythm. The sleep-wake cycle only becomes entrained to the 24-hour solar day by these factors, and by far the most powerful is ocular light exposure. The use of exogenous melatonin is one of the major non-light factors that can entrain the circadian rhythm, but results in clinical samples have been mixed.

 This is not surprising because there can be great individual variability in endogenous melatonin production. Light, medication, and behavior can also change melatonin levels. The pharmacokinetics and pharmacodynamics of exogenous melatonin (high first-pass metabolism, short half-life, and weak MT1/MT2 receptor binding) may also lead to the inconsistent effects in many clinical spheres as well.

Melatonin appears to have 2 probable interacting effects on the sleep-wake cycle. First, it entrains and shifts the circadian rhythm (process C) in a “chronobiotic” function. Second, it promotes sleep onset and continuity in a “hypnotic” function by increasing the homeostatic drive to sleep (process S). These effects appear to be equal. Clinically, exogenous melatonin given in the morning delays the phase of circadian rhythm and subsequent evening sleepiness. Melatonin given in the evening can advance both of these phases.

Light exposure has the opposite effect and is much more potent in its phase-shifting effects. This can also vary depending on the exact time the melatonin is given and light exposure occurs, in relation to the circadian rhythm of the patient. Patients demonstrate more compliance in taking melatonin at the right time than in pursuing the necessary exposure to light. Thus, timed melatonin administration may be a more viable way to change the circadian rhythm in clinical practice when needed.

A circadian rhythm disorder is defined as a persistent or recurrent pattern of sleep disturbance primarily caused by alterations in the circadian timekeeping system or a misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep. This definition takes into account that both exogenous (lifestyle, job, social and cultural factors) and endogenous (biological circadian rhythm) can contribute to the misalignment. (Details can be found in 

Evaluation and treatment of circadian rhythm sleep disorders

Many of the inhibitory pathways of melatonin synthesis and secretion and the SCN use Î³-aminobutyric acid (GABA) as the neurotransmitter. Hence, medications that affect the GABA receptors, such as benzodiazepines, or increase GABA tone, such as valproate, can reduce melatonin secretion at night. -Blockers, prostaglandin inhibitors, and dihyropyridine calcium antagonists can profoundly reduce melatonin levels as well.


	Clinical screening questions for circadian rhythm disorders

) and the Morningness-Eveningness Questionnaire

 are not supported by formal evidence but are useful to alert the clinician to the patient’s preferred circadian rhythm and the possibility of resultant disorders. A sleep log or diary or the more detailed actigraph measurements are often used as a starting point for objective investigations. Actigraphy, a noninvasive way to approximate the sleep-wake cycle, measures gross motor activity by a sensor usually placed on the wrist. Review of data from a sleep log or actigraphy for 7 days is a criterion for diagnosis of a circadian rhythm sleep disorder. A full sleep study (polysomnography) is not routinely recommended unless there are signs and symptoms of another, more common primary sleep disorder (eg, obstructive sleep apnea), but it is important to inquire about the potential of these disorders.

The use of timed melatonin is indicated with varying degrees of evidence in all circadian rhythm sleep disorders.

 Melatonin is used in conjunction with or instead of other treatments, such as timed light exposure, planned sleep schedules, and stimulants. The time of administration and, to some degree, the dose of melatonin depend on the disorder being treated (

). Dosages have been quite variable (0.3 to 10 mg), but as a rule it is best to use the lowest effective dose. Lower doses (1 to 3 mg) are best for delayed sleep phase syndrome and higher doses (5 to 10 mg) are better for jet lag sleep disorder, shift work sleep disorder, and free-running disorder.

It is well known that insomnia is an extremely common concern, especially in psychiatric illness. It has multiple deleterious sequelae and large direct and indirect economic costs. A significant proportion of insomnia cases are either due to or comorbid with a secondary cause. Primary insomnia, or a component of it, is only diagnosed when all other factors have been ruled out or fully optimized.

The initial clinical approach to managing insomnia is to rule out, or treat, all secondary causes and comorbidities, primary sleep disorders, and sleep-interfering behavioral concerns. The importance of vigilance for evolving secondary causes (especially mood and anxiety disorders) when treating patients with insomnia cannot be overstated. Insomnia is a strong risk factor for these disorders and may represent an early form of the illness.

Both cognitive-behavioral therapy and hypnotic medications have been the main treatment modalities for primary insomnia. Approved hypnotic medications include benzodiazepines and benzodiazepine receptor agonists such as eszopiclone, zolpidem, and zaleplon. Numerous adverse effects have been seen with benzodiazepines, including amnesia, next day hangover, cognitive effects, and rebound insomnia, which makes their use controversial. Benzodiazepine receptor agonists attenuate these features, but they are still troublesome. The wide off-label clinical use of sedating antidepressants, antipsychotics, and antihistamines for sleep concerns points not only to the inadequacy of current medications for treating primary insomnia but also to possible clinical misdiagnosis of the primary insomnia state or even the lack of identification of key comorbidities.

There are mixed results for the use of exogenous melatonin in primary insomnia. Definite trends toward the efficacy of melatonin were seen in one meta-analysis.

 Results from another study reported as negative actually demonstrated a statistically significant positive result of a decrease in sleep latency by an average of 7.2 minutes for melatonin.

 For reasons that are unclear, this result was considered clinically insignificant, although such improvement in sleep latency is well within the range of other marketed pharmaceutical hypnotic agents.

Study findings from large groups of middle-aged and elderly patients indicate a clear improvement in primary insomnia with the use of 2 mg of extended-release melatonin. In the largest study of more than 500 patients, positive results were primarily seen in patients aged 55 and older and efficacy was seen over a 6-month period.

 The preferential result of exogenous melatonin in an older population may be linked to an age-related decrease in melatonin levels. Some possible causes of this include less effective light input, a decrease of activity of the SCN, or calcification of the pineal gland. Support for this mechanism comes from a study of patients of all ages with relatively low melatonin levels who showed preferential response to the sleep effects of exogenous melatonin.

Extended-release melatonin has also been found to be safe and well tolerated.

 No significant withdrawal, cognitive adverse effects, or rebound insomnia were seen. These are universally consistent findings in all of the studies of exogenous melatonin in insomnia.

 As a result of the findings from the studies mentioned above, extended-release melatonin has been indicated by the European Medicines Agency and a number of regulatory agencies in other countries as a monotherapy for the short-term treatment of insomnia in patients aged 55 and older. Given the low risk of adverse effects with short-term use and the excellent safety profile, a recent consensus statement from the British Association for Psychopharmacology went a step further and concluded that “a controlled-release formulation of melatonin is the first-choice treatment when a hypnotic is indicated in patients over 55.”

Ramelteon, a newer MT1/MT2 melatonin receptor agonist approved by the FDA in 2005 for the treatment of insomnia, has addressed some of the intrinsic biological problems linked to the inconsistent findings of melatonin on sleep. It has a much longer half-life than exogenous melatonin and has a 3- to 16-fold greater affinity for the MT1 and MT2 receptors.

 It has greater lipophilic properties than melatonin, with increased tissue absorption and an active metabolite that contributes to its action. Most of the action of ramelteon is specifically on the SCN, and it has no affinity for benzodiazepine, opioid, dopamine, or serotonin receptor subtypes.

 It is also MT1 receptor- selective, which suggests that it targets sleep onset more than melato-nin itself.

Ramelteon is clearly effective for treating primary insomnia at a wide dose range (4 to 32 mg) on multiple variables of sleep in patients aged 18 and older, including patients older than 65. Effects occurred as quickly as 1 week and efficacy was seen over 6 months, without significant next morning residual effects, rebound insomnia, cognitive adverse effects, and withdrawal.

 A number of studies also indicate a dose-independent effect of ramelteon, which suggests a more regulatory than sedative mechanism of improving sleep.

Melatonin has a role in psychiatric illness and the treatment of circadian rhythm sleep disorders, insomnia, and comorbid depressive disorders.

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A Review of Changes in DSM-5 Sleep-Wake Disorders

What’s New Under the Moon-Insomnia and Sleep Deprivation

The Correlation Between Sleep-Disordered Breathing and Psychiatry

The Role of Melatonin in the Circadian Rhythm Sleep-Wake Cycle

Introduction: Understanding Common Sleep Disorders in Psychiatric Illness

ADHD and Sleep Disorders in Children

Comorbid Sleep and Psychiatric Disorders: Rx of the Former Can Improve the Latter

Sleep Disorders Quiz