Clinical manifestations

Presentation and course

Sleep complaints are common in general medical, psychiatric, and neurologic clinics. Common sleep symptoms include insomnia or hypersomnia, nightmares, and excessive nighttime movements. Although sleep symptoms may be due to specific sleep pathology, they are often a symptom of another condition, including psychiatric disorders. One third of patients presenting to sleep centers have a primary psychiatric diagnosis; in community-based surveys, primary psychiatric disorders, most commonly mood disorders and anxiety, are present in up to 40% of patients presenting with insomnia (14; 09).

Many psychiatric conditions include sleep-related complaints (see table 1). Patients can present with problems initiating or maintaining sleep, problems with sleep quality (ie, not feeling rested), daytime hypersomnolence or added movements, or sleep behaviors.

Table 1. Psychiatric Disorders with Sleep Symptoms

Class	Psychiatric disorders	Sleep complaints	Observed changes in sleep architecture
Mood disorders	Major depressive disorder	Hypersomnia, insomnia, early awakening	Prolonged sleep latency, increased REM density
	Bipolar affective disorder	In mania: decreased need for sleep	Reduced total sleep time; shortened REM latency
Anxiety disorders	Generalized anxiety disorder	Insomnia, poor sleep quality	Increased sleep latency, decreased sleep continuity
	Panic disorder	Nocturnal panic attacks	Non-REM panic attacks; longer sleep latency, reduced total sleep time, reduced sleep efficiency
	Separation anxiety disorder	Difficulty sleeping without attachment figure nearby	Insufficient data
Psychotic disorders	Schizophrenia	Insomnia	Reduced sleep depth and sleep continuity
	Schizoaffective disorder	Decreased need for sleep/total sleep time with mania	Insufficient data
Substance use disorders	CNS depressants (alcohol, opiates, sedative-hypnotics) intoxication and with chronic use	Insomnia, hypersomnia (depending on pattern of use and time from last dose)	Insufficient data
	CNS stimulants (cocaine, amphetamines)	Insomnia/hypersomnia, (depending on pattern of use)	Insufficient data
Trauma-based disorders	Posttraumatic stress disorder	Insomnia, nightmares	Reduced sleep continuity, less sleep depth, and changes in REM sleep
	Acute stress disorder	Insomnia, nightmares	Insufficient data
	Adjustment disorders	Insomnia, poor sleep quality	Insufficient data
Neurodevelopmental disorders	Autism spectrum disorder	Insomnia, poor sleep quality	Reduced sleep efficiency, decreased REM and slow wave sleep duration
	Attention deficit and hyperactivity disorder	Insomnia, sleep-disordered breathing and restless legs syndrome/periodic limb movements, treatment-related insomnia	Insufficient data
Neurocognitive disorders	Alzheimer disease and other dementias	Abnormal sleep-wake cycles	Abnormal circadian rhythms (day/night reversal), fragmented sleep
	Diffuse Lewy body dementia and Parkinson disease	Movements during sleep, acting out dreams	REM sleep behavior disorder
Disorders of consciousness	Delirium	Abnormal sleep-wake cycles	Abnormal circadian rhythm, high arousal and awakening index, reduced slow wave sleep and REM sleep

Mood disorders.

Depression. Sleep disturbances (insomnia or hypersomnia) and fatigue are among the diagnostic criteria for major depressive episodes (03). A study of more than 3700 adults with major depressive disorder found that nearly 85% of patients reported symptoms of insomnia (84). Twenty-seven percent of patients reported experiencing all 3 of the major types of insomnia (sleep-onset, mid-nocturnal, and early morning insomnia), with mid-nocturnal insomnia being the most commonly reported type. In a large, community-based cohort study of elderly persons, both short-duration (less than 6 hours per night) and long-duration (9 or more hours per night) sleepers were more likely to have a depressive disorder, including major depressive disorder, minor depressive disorder, or dysthymia, than those sleeping 7 to 8 hours per night (91). Depressed patients also spent more time in bed than those without depression in this study.

Subjective sleep complaints and objective findings in depressed patients may not always coincide. In 2 studies, both nefazodone and fluoxetine alleviated depression and resulted in subjective improvement in sleep quality, although the patients given fluoxetine showed worsening in objective sleep parameters (36; 79). Analogous findings are also seen in patients whose depression was treated with psychotherapy; compared to controls, the treated patients had more objectively assessed arousals from sleep, but reported subjective improvements in sleep quality and mood (10).

Pharmacological treatment of depression is associated with parasomnias, particularly sleepwalking and rapid eye movement sleep behavior disorder. Many of the cases of REM sleep behavior disorder symptoms in psychiatric patients are due to serotonergic antidepressants rather than to idiopathic REM sleep behavior disorder. Sleepwalking can be triggered by tricyclic antidepressants and nonbenzodiazepine receptor agonists such as zolpidem (49).

Bipolar affective disorder. Sleep disturbance is a cardinal feature of bipolar disorder and part of the diagnostic criteria. During acute mania, patients exhibit markedly reduced sleep time and report a reduced need for sleep. The reduced need for sleep can be further defined as the “ability to maintain energy without sufficient sleep” (71). Sleep restriction due to occupation or travel can precipitate a manic episode. Even when euthymic, sleep disturbance is common and may affect daytime functioning (39). Both insomnia and hypersomnia have been reported in patients with bipolar depression (39).

Schizophrenia. Many patients with psychosis have complaints about their sleep, usually due to a problem of sleep onset and maintenance insomnia. The complaint may also involve unsatisfactory sleep related to fragmentation and schedule changes brought about by acute psychosis. In addition, the persistence of sleep complaints in treated schizophrenia is associated with a greater risk of recurrence of psychotic symptoms after antipsychotic withdrawal (18).

Anxiety disorders. Sleep complaints are common in anxiety disorders. Symptoms of insomnia are reported by more than 75% of patients with generalized anxiety disorder (06). Objective studies suggest that patients with generalized anxiety disorder have decreased total sleep time and increased latency to sleep, which correlates with patient reports of ruminating when trying to fall asleep (23).

Similarly, 70% of patients with panic disorder also report sleep disturbances (67). Patients with panic disorder exhibit increased sleep latency and decreased efficacy, with decreased total sleep time. Patients may experience nocturnal panic attacks that may further disrupt sleep (23).

Trauma-based disorders. Up to 90% of patients with posttraumatic stress disorder report problems with sleep (59). Indeed, nightmares are a diagnostic feature of posttraumatic stress disorder as found in DSM-5 (03). The range of sleep changes after trauma extends beyond nightmares and includes insomnia, frequent awakenings, decreased sleep efficiency, and disruptive sleep behaviors. Conditions such as periodic limb movement disorder and obstructive sleep apnea are frequently comorbid with posttraumatic stress disorder (23; 57).

Neurodevelopmental disorders.

ADHD. Parents commonly report sleep problems in their children with attention deficit hyperactivity disorder (ADHD). Compared with controls, children with the combined type of ADHD have significantly greater difficulties with enuresis, decreased total sleep time, and increased sleep latency (55). Children with the inattentive type may sleep more than normal and have greater daytime sleepiness than controls (55). Children with ADHD have more movements in sleep than controls (22). Although sleep disturbances may impact up to 70% of children with ADHD, the relationship is complicated and likely multifactorial. Sleep problems may be part of the ADHD pathology, treatment of ADHD with stimulant medications, or comorbid conditions such as sleep apnea that may mimic or exacerbate ADHD symptoms (89).

Autism. Sleep disturbances are found in over 70% of children with autism. Sleep studies indicate reduced sleep efficiency, less slow wave and RME sleep, and more desaturations (01).

Substance use disorders. Exogenous substances that alter excitatory or inhibitory pathways have the potential to disrupt sleep both acutely and chronically. CNS depressants can initiate sleep acutely but also lead to rebound excitation. Often, alcohol is used to initiate sleep. However, chronic alcohol use is associated with changes in sleep onset and maintenance (12). Complaints of hypersomnia, fragmented sleep/wake cycle, and parasomnias may also occur. Alcohol use disorder is also associated with obstructive sleep apnea. Independent of other factors, insomnia is also a predictor of relapse to alcoholism (12; 17). Psychostimulants such as amphetamines or cocaine can inhibit sleep and lead to hypersomnia during withdrawal states.

Prognosis and complications

Sleep disturbances complicate the clinical course of psychiatric disorders. They are associated with poor response to psychotherapy and pharmacotherapy for depression (26; 88; 15; 77) and negatively impact functioning in posttraumatic stress disorder (20; 46). Long (≥ 10 hours) and short (≤ 6 hours) sleep duration is associated with persistence of anxiety and depression over a 2-year period (92). Insomnia, nightmares, and other sleep disturbances are associated with an increased risk for suicidal ideation, suicide attempts, and completed suicide (69). Treatment of the psychiatric disorder does not always lead to improvements in sleep, as observed in studies of patients with depression (60) and posttraumatic stress disorder (07). Indeed, insomnia is the most commonly reported residual symptom of depression (41). Individuals who report residual sleep disturbances following remission of depression have a poorer quality of life (51) and an increased risk for relapse (29; 28). In these cases, sleep disturbance may persist secondary to the development of perpetuating factors such as substance abuse, poor sleep hygiene, or psychophysiological insomnia, or as a consequence of the medications used to treat the psychiatric disorder. Therefore, independent treatment of sleep disturbance is warranted for some patients, particularly those whose sleep problems persist after their psychiatric condition has remitted.

Importantly, sleep disorders such as insomnia (80) and sleep-disordered breathing (96) can be successfully treated in individuals with psychiatric illness. A major complication of sleep disorders associated with psychiatric illness is a missed diagnosis of a treatable but morbid organic condition such as obstructive sleep apnea. If the psychiatric diagnosis is pursued alone, a "refractory" case results, leaving the undiagnosed organic pathology to worsen. Similarly, patients presenting with insomnia should be screened for other conditions such as anxiety, depression, and trauma-based disorders as well.

Clinical vignette

JW, a single, 25-year-old female with bipolar type I disorder, had been relatively stable for 3 years on a regime of lithium 600 mg twice daily and Ambien (zolpidem) 10 mg at bedtime. She had not had a distinct mood episode since her last episode of bipolar mania 3 years prior. She obtained 7 to 8 hours of sleep at night and was satisfied with her job as a respiratory therapist working for a durable medical equipment company.

After the company went out of business, JW took a job as a sleep technician working for a growing sleep disorders center. The new job involved working 8 pm to 6 am Tuesday through Friday. JW was only able to sleep 5 to 6 hours after her shift, even with the aid of zolpidem. She slept about 7 hours on nights she was not working.

Three days prior to presentation, JW felt unusually energized as she was finishing her shift. She drove home and spent the next 16 hours cleaning her house from top to bottom. JW then slept for an hour and went to a dance club. She left the dance club when it closed at 3 am and returned to her house, where she slept for 2 hours. She exercised extensively the next day and showed up at the sleep center that night. She told her coworkers she was there because she was now the owner of the sleep center and she wanted to make sure they were doing their jobs right. She was talking rapidly and pacing. JW became agitated when the other sleep technicians refused to take orders from her. The medical director was called. He, with great difficulty, was able to convince her to go to the emergency room. The medical director and a technician drove her to the emergency room, where treatment was begun for a manic episode.

Comment. JW developed a manic episode with symptoms of grandiosity, decreased need for sleep, rapid speech, and increased goal-directed activity. A change in sleep habits can precipitate a bipolar mood episode. Night work and shift work have a destabilizing influence on bipolar disorder.

Biological basis

Etiology and pathogenesis

The etiology of sleep abnormalities in psychiatric disorders is not fully understood and likely differs based on the specific disorder. In many cases, the neurologic mechanisms believed to be dysfunctional in psychiatric disorders overlap with those involved in arousal regulation, and this dysfunction directly leads to sleep abnormalities. In some cases, circadian rhythm abnormalities, elevated physiological arousal, and excessive rumination play a significant role. Both homeostatic and circadian sleep abnormalities are thought to play a role in bipolar disorder (71). Sleep changes may precede and contribute to the development of mood disorders (68).

Genetic studies consistently indicate that complex polygenic inheritance and environmental factors both contribute to vulnerability to psychiatric disorders; genetic factors are particularly prominent in bipolar affective disorder. Concordance rates for monozygotic twins is up to 90% in bipolar disorder and 50% in major depressive disorder; for dizygotic twins the concordance rates are about 25% (43). Higher concordance rates are found in monozygotic twins in generalized anxiety disorder, schizophrenia, and alcoholism. The genetic substrate appears to overlap for some psychiatric disorders. The Stin2.12 allele of the serotonin transporter gene predisposes to generalized anxiety disorder, obsessive compulsive disorder, and major affective disorder (65); a locus on chromosome 1 was demonstrated to predispose to alcoholism and depression (62).

Benca and colleagues have reviewed polysomnographic findings in psychiatric disorders (08). Patterns in depression consist of disturbances in sleep continuity (increased latency, decreased sleep efficiency, increased awakenings with early morning awakenings), abnormal distribution of slow-wave sleep, and abnormalities of rapid eye movement sleep (reduced REM latency, abnormal distribution of REM sleep with increased REM percentage of total sleep time, and increased REM density). High-density electroencephalography has shown that females with depression have increased slow-wave activity in bilateral prefrontal regions relative to healthy controls, whereas there are no differences in slow-wave activity between depressed males and healthy controls (70). Continuity disturbances tend to parallel the severity of depression, whereas reduced REM latency and slow-wave sleep tend to persist during remission. In anxiety disorders, the most common finding is sleep continuity disturbance, although inconsistent abnormalities of REM sleep are prominent in studies of posttraumatic stress disorder. Patients with alcohol use disorder display sleep continuity disturbances, decreased slow-wave sleep, and decreased REM sleep, and disturbances may persist after years of abstinence. Presence of insomnia is associated with higher craving for alcohol, which is reduced with sleep aids (40). The sleep patterns of schizophrenia are characterized by decreased REM latency, decreased stage 4 or slow-wave sleep, and sleep continuity abnormalities. Polysomnographic studies of unmedicated manic patients have found shortened total sleep time, shortened REM latency, and increased time awake in bed (71).

Studies utilizing functional brain imaging have shown overlap between abnormal regions involved in psychiatric disorders and regions known to be involved in sleep regulation. Abnormalities of central monoaminergic systems, especially serotonin, have been implicated in the pathogenesis of depression, and these systems play critical roles in sleep regulation (50).

There is strong evidence for muscarinic (cholinergic) involvement in short REM sleep latency. Patients with depression and schizophrenia show a substantial shortening of the already short REM sleep latency when given muscarinic agonist drugs (76; 82). Levels of an abnormal plasma cholinesterase isozyme in patients with schizophrenia correlate with REM latency (44). A polymorphism of the muscarinic receptor 2 gene was found to be associated with major depression in women (21).

Epidemiology

The lifetime prevalence of major depressive disorder is 10% to 25% for women and 5% to 12% for men. It occurs with similar prevalence across racial groups, socioeconomic classes, and age groups past about 5 years (mean age: 40 years) (43).

Approximately 1% of the general population has schizophrenia and 1% has bipolar disorder. Both have approximately equal sex ratios. Lifetime prevalence rates of anxiety disorders are estimated at 30.5% in women and 19.2% in men, with rates decreasing with increasing socioeconomic status. Onset can occur at any age. Lifetime prevalence of alcohol dependence is 3% to 5% for women and 10% for men (43).

Prevention

There is insufficient knowledge about the predisposing and precipitating environmental factors of most psychiatric disorders to allow reliable prevention of them. Some environmental associations have been reported, but causality is not clearly established. For instance, a study found that total 24-hour light exposure was negatively correlated with sleep and mood disturbances in postmenopausal women (94).

Insomnia and sleep disturbances increase risk for the first onset of depression, anxiety disorders, and substance abuse (09; 42) and predict relapse to depression and alcoholism (12; 29). Treatment of these disorders may, thus, help prevent the development of many psychiatric conditions and improve clinical course for patients whose psychiatric disorder has remitted. Early treatment and education may help prevent comorbidity (eg, substance abuse, poor sleep hygiene). Medications used to treat psychiatric disorders (eg, SSRIs, dopamine antagonists, lithium) may disrupt sleep directly.

Good sleep hygiene may prevent exacerbation of sleep disturbances. As mentioned, maintaining consistent sleep habits is especially important in preventing manic episodes in bipolar affective disorder.

Differential diagnosis

The primary differential diagnosis for sleep disorders associated with psychiatric disorders is other causes of insomnia or hypersomnia. Psychophysiological insomnia is distinguished from the anxiety disorders in that anxiety in psychophysiological insomnia is focused around the sleep environment or sleep itself. Primary sleep disorders such as restless legs syndrome, sleep apnea syndromes, or circadian rhythm abnormalities may coexist with psychiatric disorders and contribute to sleeping difficulty. Periodic limb movement disorder and obstructive sleep apnea are more common in patients with posttraumatic stress disorder than the general population (52). Obstructive sleep apnea can produce severe daytime somnolence and cognitive impairment, which together resemble psychomotor retardation, a diagnostic feature of both depression and bipolar disorder or poor concentration with ADHD. Symptoms of sleep apnea, including snorting or stopping breathing while asleep, are associated with depressive symptoms (97).

Narcolepsy shares features with several psychiatric syndromes. These shared features, especially hallucinations, can be a source of diagnostic confusion. Most patients with narcolepsy have full insight into their hypnagogic hallucinations. They are unusually realistic 3-dimensional visual hallucinations and often surface with multimodal sensory features (sound, touch, taste, smell). At times they are overlaid on perceptions of the actual environment, giving rise to delusional interpretations of ghosts and the like (31). Hallucinations in schizophrenia can include visual components but more commonly involve disembodied voices that converse with the patient, comment about him or her, or give instructions. Delusions tend to be elaborate and highly implausible, whereas psychotic patients with narcolepsy tend to restrict their delusions to a simple explanation of the repetitive hallucinations ("secondary delusions"). Occasionally, patients presenting with what appears to be hypomania (irritability, hyperactivity, rapid speech, etc.) are found to have narcolepsy after sleep laboratory testing. Such patients may never have regarded themselves as “sleepy.”

Other medical causes of sleep disturbance may coexist with psychiatric disorders, including pain disorders, prostatic hypertrophy, nocturnal asthma, cardiopulmonary disease, and hyperthyroidism. Sleep disturbances as part of psychiatric disorders must be distinguished from those associated with common comorbid conditions such as substance abuse and inadequate sleep hygiene. Medications used to treat psychiatric disorders, such as SSRIs, can disrupt sleep either directly through their activating effect or indirectly through worsening of restless legs syndrome or periodic limb movement disorder. Benzodiazepines may worsen sleep disordered breathing.

Diagnostic workup

Patients presenting with sleep complaints should receive a full evaluation with thorough medical and psychiatric review of systems. A careful sleep history is necessary to understand sleep patterns and any behaviors that may be contributing (ie, using full spectrum screens before bed, caffeine, and alcohol and other substance use, including over the counter medications).

A physical examination is important in all patients to evaluate for any signs or symptoms of any condition that may be associated with changes in sleep as primary sleep disorders can mimic some psychiatric symptoms or be co-occurring.

Daily sleep logs or diaries maintained over a 1- to 2-week period can aid in diagnosis of insomnia as suggested by subjective report of difficulty falling asleep or maintaining sleep in conjunction with daytime impairments due to poor sleep. Individuals with bipolar disorder who report difficulty falling or staying asleep or short sleep duration (eg, less than 6 hours) without daytime impairment or excessive daytime sleepiness may be experiencing mania or hypomania. Sleep logs should correlate with presentation of pressured speech, expansive affect, increased goal-directed activity, and other symptoms that are part of mania.

A polysomnogram and multiple sleep latency test may be indicated if a specific sleep disorder such as narcolepsy, periodic limb movement disorder, or sleep apnea is suspected, or in cases where the sleep disturbance persists despite treatment of the underlying psychiatric disorder. Although some psychotic patients may not easily comply with sleep laboratory procedures, most such patients can be studied if given more attention by the technicians.

Management

The management of sleep disturbance in psychiatric disorders depends first on appropriate diagnosis of the psychiatric disorder and ruling out other pathologies that contribute to sleep. In the situation of sleep disturbances in the context of a psychiatric disorder, treatment of that disorder should occur. Cognitive and behavioral therapy as well as supportive psychotherapy play a significant role in the management of many disorders, often combined with pharmacological therapy or alone.

Patients with major depressive disorder typically receive a combination of medication and/or psychotherapy. SSRIs and other agents, such as venlafaxine, bupropion, and mirtazapine, are the most widely prescribed medications for treatment of depression and have largely replaced tricyclics and monoamine oxidase inhibitors because of their safety and favorable side-effect profiles. Treatment with SSRIs may improve sleep as the mood disorder improves; however, with all antidepressants, there is a lag of 4 to 6 weeks to see effect. Specific medication choice can be guided by the presence of sleep problems. Patients with insomnia may do well with a sedating medication such as mirtazapine (due to anti-histamine effects) or paroxetine (anticholinergic effects). Patients with hypersomnia may respond to activating medications such as bupropion or venlafaxine, which may improve energy. Treatment with an antidepressant as well as another medication to target sleep can also be attempted and is discussed further below.

Bipolar disorder is treated with mood stabilizing agents such as lithium, divalproex, or carbamazepine or an antipsychotic such as quetiapine. Often, such agents are sedating and are administered at night to aid in preserving sleep. Addition of an antidepressant may be necessary for bipolar depression, although quetiapine is approved as monotherapy and sufficiently sedating. Because of the importance of sleep in maintaining euthymia, adjunctive medications for sleep may be added and have fewer side effects than mood stabilizers. For example, ramelteon, a melatonin receptor agonist, has been shown in a small study to improve mood stability in patients with bipolar disorder (61).

The maintenance of a stable sleep/wake cycle and regularization of the circadian rhythm are key components of an effective psychotherapy for bipolar disorder, interpersonal, and social rhythm therapy. Daily sleep diaries can be helpful to track the sleep/wake cycle in patients with bipolar disorder. Interpersonal and social rhythm therapy is most effective for mood episode prophylaxis in the maintenance phase of bipolar disorder and in individuals without significant medical comorbidity or anxiety (34). A pilot study found that “dark therapy,” which is 14 hours of enforced darkness from 6 pm to 8 am for 3 consecutive nights, was a useful add-on therapy for inpatients with bipolar mania (05).

SSRIs are first-line treatment for anxiety disorders. Posttraumatic stress disorder is also treated with SSRIs. Prazosin, an alpha-1 adrenergic antagonist, has some evidence to support its use to prevent nightmares at doses of 1 to 20 mg/day in several small studies, and it decreased the intensity and frequency of posttraumatic stress disorder-related nightmares, as well as improved subjective sleep quality (27). A study did not show an effect of prazosin to combat posttraumatic stress disorder (73).

The sleep disturbances in schizophrenia often respond to antipsychotic drugs (48). Quetiapine, clozapine, and olanzapine are particularly sedating, whereas risperidone and aripiprazole are less sedating. When sleep disturbance is prominent, the majority of antipsychotic drug dosage can be given at bedtime.

Managing sleep problems in substance use disorders is complex and depends on the context. Patients undergoing alcohol detoxification who are restless and cannot sleep should be treated with benzodiazepines as the insomnia is a function of GABAergic withdrawal state. Gabapentin is sometimes used as an adjunct for detoxification or for maintenance of sobriety and may improve sleep in individuals with alcohol use disorders (54). Sleep disturbances take a minimum of 3 to 6 months to normalize with sobriety (13).

Cognitive behavioral therapy for insomnia (CBTi) is a highly effective nonpharmacological treatment option for insomnia (58). Typically, short-term (4 to 8 sessions), cognitive behavioral therapy for insomnia integrates cognitive and behaviorally based treatment modalities to target the factors believed to perpetuate insomnia. The behavioral components consist of sleep restriction, stimulus control procedures, and relaxation training. The cognitive component of therapy consists of educating the patient about the role of negative sleep-related thoughts in perpetuating sleep problems. Patients are also educated about sleep hygiene, which refers to daytime habits (eg, exercise, napping, substance use close to bedtime) and environmental circumstances (eg, temperature regulation, bed comfort) that can help or hinder sleep.

Treatment of insomnia using cognitive behavioral therapy for insomnia improves sleep in patients with comorbid psychiatric conditions, including depression, posttraumatic stress disorder, and alcoholism (04; 53; 85). For individuals with depression, it enhances treatment response to antidepressant medications and improves remission rates (53).

Internet-based cognitive behavioral therapy for insomnia has been studied and found to be an effective treatment for insomnia (32). Unguided, digitally-delivered cognitive behavioral therapy for insomnia has effects that persist up to 18 months after intervention (93). Treatment of insomnia with computer-based cognitive behavioral therapy for insomnia was found to reduce incident depression at 1-year follow-up (19).

Mindfulness-based cognitive therapy is another nonpharmacological treatment option for sleep disturbance in individuals with depression. In this treatment, individuals are trained in mindfulness meditation and engage in meditation exercises for approximately 45 minutes per day. Eight weeks of mindfulness meditation has been associated with improvements in subjective and objective sleep continuity in individuals with depression and sleep complaints (11).

Two forms of cognitive behavioral therapy for posttraumatic stress disorder, cognitive processing therapy and prolonged exposure, improve sleep quality, though typically not to the “normal” range (35). Cognitive processing therapy consists of (1) the identification and challenging of distorted thoughts and interpretations regarding the trauma and (2) the writing by patients of detailed accounts of their traumas, which the patients read to themselves and their therapists (75). Prolonged exposure therapy consists of psychoeducation, breathing retraining, behavioral exposure to feared trauma reminders in the environment, and imaginal exposure to the memory of the trauma (75).

Imagery rehearsal therapy, recently developed therapies targeting nightmares and sleep disturbance in individuals with posttraumatic stress disorder, improves sleep, nightmares, and daytime functioning (45; 24; 16). Combining imagery rehearsal therapy and cognitive behavioral therapy for insomnia results in greater improvement in sleep quality than imagery rehearsal alone (16).

Continuous positive airway pressure (CPAP) is the gold-standard treatment for sleep disordered breathing. Treatment of sleep disordered breathing using CPAP in individuals with depression is associated with reduction in depression symptoms, even in patients whose depression was resistant to pharmacotherapy (38).

Pharmacological therapy beyond agents used to treat the underlying psychiatric disorder may benefit some patients. Medications for sleep can be divided into GABAergic medications, melatonin/agonists, sedating antihistamines, and more recently, orexin-antagonists.

Benzodiazepines or benzodiazepine receptor agonists, such as zolpidem or zaleplon, may be used, preferably on a short-term or intermittent basis. They should be avoided in any patients who have a history of alcohol or sedative/hypnotic use disorders, the elderly, or patients with respiratory disease. The benzodiazepine receptor agonist eszopiclone has been studied in patients with coexisting insomnia and major depressive disorder. During an 8-week trial involving this population, eszopiclone combined with fluoxetine improved wake time after sleep onset, total sleep time, sleep latency, and depression rating scale scores compared to patients taking fluoxetine alone (33). In addition to being studied in patients with coexisting major depressive disorder and insomnia, eszopiclone has also been shown to be an effective hypnotic in patients with generalized anxiety disorder and coexisting insomnia (72).

Alternately, a low dose of a sedating antidepressant such as trazodone may be used to treat insomnia associated with major depressive disorder. Trazodone sedates due to its antihistamine binding without anticholinergic effects. Melatonin and agonists can be helpful especially in children with ADHD.

A novel target for hypnotics is the neuropeptide orexin. Also known as hypocretin, orexin regulates wakefulness, arousal, as well as appetite. Blocking both orexin receptors 1 and 2 in combination leads to increases in REM and non-REM sleep. The first FDA-approved orexin-antagonist was suvorexant, and more recently, lemborexant (56). In phase 3 clinical trials, lemborexant was well-tolerated and improved sleep onset and maintenance compared to placebo and zolpidem (78).

Special considerations

Pregnancy

Symptoms of depression and anxiety, along with their associated sleep disturbances, may be worsened by pregnancy but tend to be particularly severe in the postpartum period. Women are at particular risk for sleep disordered breathing during pregnancy due to physiological changes (63). Snoring, a cardinal symptom of sleep disordered breathing, is associated with increased risk for depression symptoms during pregnancy (64). Poor sleep quality during pregnancy and postpartum are associated with symptoms of depression and anxiety (30). For women with a prior history of depression, experiencing poor sleep quality in the early postpartum period increases risk for relapse (66). Treatment of insomnia using cognitive-behavioral therapy is associated with improvements in both sleep and postpartum depression symptoms (86). The scant data available on the safety of medications for sleep disturbance in pregnant women suggest increased risk for adverse birth outcomes (95). Some of the medications used to treat psychiatric disorders are contraindicated in pregnancy, and for others the benefit must be balanced against the potential risks.