Clinical manifestations

Presentation and course

The DSM-5-TR differentiates anxiety from fear. Although fear is the emotional response to a real or perceived imminent threat, anxiety is the anticipation of a future threat. Fear is more associated with the well-known fight or flight response from activation of the autonomic arousal system, whereas anxiety exhibits more vigilance, tension, and restlessness. Both of these emotional states become pathological when they no longer serve an appropriate function, and they start to cause pervasive distress or impairment of day-to-day functions and social interactions. These emotional responses and associated behaviors can be provoked by a variety of objects, events, and situations.

Anxiety and fear-based disorders are frequently associated with sleep complaints, notably, difficulty initiating and maintaining sleep, restless nonrestorative sleep, and short sleep duration. One of the diagnostic criteria for anxiety includes a report of sleep disturbance, which can vary from insomnia, restlessness, or unsatisfying sleep. For example, between 70% to 90% of individuals suffering from PTSD report a sleep disturbance, including nightmares and insomnia. PTSD has also been found to be associated with obstructive sleep apnea (OSA) (27). This relationship is bidirectional, in that anxiety disorders are associated with causing sleep issues and sleep issues can bring on anxiety disorders. Chronic sleep problems are also a risk factor for developing anxiety disorders. Some studies have highlighted the independent and bidirectional relationships between anxiety, fear, and sleep disturbances. Cousins found, in youth aged 8 to 16 years, a relationship of daytime affect to subsequent nighttime sleep (10). In addition, more time asleep during the night was associated with more positive next-day affect (10). This bidirectional relationship has been more recently shown with the COVID pandemic. Since the COVID-19 pandemic, there have been several studies looking at stress, anxiety, and sleep problems stemming from its aftermath. There have been between 20% to 45% of reported insomnia cases during the pandemic (03). These studies have shown that there are now higher rates of insomnia, stress, anxiety, and depression than previously noted since the start of the pandemic (28). Research has historically shown that stressful events have a more profound impact on individuals with insomnia than those with normal sleep. One study found that individuals with acute insomnia symptoms during the pandemic had a stronger likelihood of having anxiety and depression than in individuals with preexisting or chronic insomnia (03). Sleep problems were also seen in individuals who contracted COVID-19. Individuals who were hospitalized with the infection for 7 or more days complained of disturbed sleep and excessive daytime sleepiness, and these symptoms lasted for months after recovery (03).

Each anxiety and trauma disorder have varying presentations in their sleep disturbances. Definitions for these disorders are based on the DSM-5-TR criteria. These presentations are described below:

Generalized anxiety disorder. Anxiety is the most common mental health disorder, with a global prevalence of around 25% (09). The defining feature of generalized anxiety disorder is excessive anxiety and worry occurring for at least 6 months on most days in various environments, such as school or work. These individuals find it difficult to control these feelings, thus causing disruption in their day-to-day life. Many of these patients find these pervasive thoughts persisting into their bedtimes, thus affecting their sleep. They often report sleep initiation and maintenance insomnia.

Panic disorder. Sleep problems are common in panic disorder. Individuals with severe panic disorder have significantly higher prevalence of insomnia (24). Sleep onset problems may be particularly pronounced among panic disorder patients with high levels of anxiety sensitivity, defined as excessive fear of anxiety-related sensations (22).

Panic disorder is characterized by recurrent and unexpected panic attacks, which are sudden increases in intense fear or discomfort that reaches a peak within minutes. Patients often endorse palpitations, sweating, chest pain, sensation of dyspnea, trembling, nausea, abdominal discomfort, or dizziness. Some may also have a feeling of losing control or uncontrolled fear of dying. These episodes tend to be self-limiting and brief, usually lasting from 10 to 30 minutes.

Panic attacks can occur as a part of various mental disorders, or they can be isolated events. Panic attacks can occur in the transition between wake and sleep. Sleep complaints tend to be most severe in patients with nocturnal panic attacks, which are recurrent in 33% of patients (19). Nocturnal panic attacks begin with an abrupt arousal from sleep without dream mentation and are accompanied by panic attack symptoms that are similar in severity and duration to panic attacks experienced while awake, although in some patients, panic attacks may be experienced predominantly or exclusively during sleep (37). These nocturnal episodes are distinguishable from sleep terrors, sleep apnea, nightmares, or dream-induced arousals by the fact that the patients with panic become fully awake and aware of their surroundings and have memory for the events. In some patients, nocturnal panic attacks may lead to a phobic fear of the sleep environment or sleep itself, leading to avoidance of sleep.

Social and specific phobia. Individuals with social phobia have marked and persistent fear of one or more social situations where they may be scrutinized by others. Specific phobias exhibit the same persistent fear, but for specific objects or situations. These individuals do not tend to have sleep problems, unless the contents of their phobia is related to sleep. Although little systematic investigation has been conducted, one study found that as many as two thirds of a sample of treatment-seeking patients with social phobia reported insomnia symptoms, with one third falling in the moderate to severe range (34).

Posttraumatic stress disorder. Posttraumatic stress disorder (PTSD) is diagnosed when an individual is exposed to an actual or threatened death, serious injury, or sexual violence, and begin to have recurrent and intrusion memories of these events. This includes intrusive dreams or nightmares. Individuals will attempt to avoid these stimuli linked to the traumatic event, thus leading to avoidance of sleep to prevent a nightmare. A systematic review of nightmares in individuals with psychiatric conditions suggested that the presence of nightmares lead to an increased the risk of suicidality and that treatment of the nightmares could mitigate that risk (39).

In addition to a high prevalence of nightmares in patients with PTSD, dream enactment behavior (DEB) is also noted to be common in these patients (26). REM sleep behavior disorder (RBD) is the phenomenon of the loss of atony with punching, kicking, yelling, and/or screaming in REM sleep corresponding with dream content. REM sleep behavior disorder can also be seen in patients with obstructive sleep apnea or patients on antidepressants. Dream enactment behavior along with REM sleep without atonia (RSWA) is seen on polysomnography. REM sleep behavior disorder is associated with the development of a group of disorders known as alpha-synucleinopathies, including Parkinson disease, multiple system atrophy, and dementia with Lewy bodies (42). Interestingly, Feemster and colleagues in a retrospective study showed that patients with PTSD had increased RSWA regardless of the presence or absence of dream enactment behavior (15). This was also true in patients with PTSD whether or not they were on concurrent antidepressants.

Individuals with PTSD were also noted to be at an increased risk for sleep-disordered breathing, specifically obstructive sleep apnea. One study suggested that around 40% to 90% of individuals with PTSD also suffered from obstructive sleep apnea (27). When screening for obstructive sleep apnea, these individuals often do not report excessive daytime sleepiness due to their hyperarousal/hypervigilance state, thus masking the daytime symptoms normally seen with obstructive sleep apnea. A thorough history and contributory information for a bed partner is crucial until a formal polysomnogram can be performed. Around one third of individuals with PTSD were also diagnosed with periodic limb movement disorder (PLMD), which led to increased arousals and awakenings (27).

Polysomnography data. Polysomnography in individuals with anxiety and trauma based disorders tend to be consistent with subjective complaints of poor sleep.

A 2018 study looking at time of day effects on sleep and anxiety showed that decreased total sleep time relative to personal average total sleep time predicts subsequent anxiety (11). It has also been reported that individuals with GAD had increased sleep onset latency (SOL) and increased wake after sleep onset (WASO) and reduced sleep efficiency (37). This result is consistent with previous studies looking at adolescents with GAD where they found decreased total sleep time and increased morning anxiety (30). For PTSD, studies have had inconsistent results on effects of total sleep time and severity of PTSD symptoms (11). Studies have shown that individuals with PTSD had more stage N1 sleep and REM sleep, but had less slow-wave-sleep (stage N3) as compared to healthy controls (37). These studies also found consistent sleep fragmentation with individuals with PTSD.

Diagnosis of sleep disorders in patients with anxiety. Individuals with anxiety disorders whose sleep disturbances are severe may qualify for a comorbid sleep disorder diagnosis. The primary diagnosis seen in these individuals is insomnia disorder. Prior to the DSM-5, “insomnia due to mental disorder” was used for diagnosis; however, the DSM-5 replaced this with “insomnia disorder” (02). The DSM-5-TR differentiates between episodic (symptoms lasting 1 to 3 months), persistent (symptoms lasting longer than 3 months), and recurrent insomnia (two or more episodes within the space of 1 year).

Specific criteria for the diagnosis of insomnia disorder per the DSM-5 TR includes:

The text revision of the third edition of the International Classification of Sleep Disorders (ICSD-3-TR) defines insomnia disorder as a persistent difficulty with sleep initiation or maintenance that is associated with concern, dissatisfaction, or perceived daytime impairment, such as fatigue, poor mood, irritability, or cognitive changes (01). The ICSD-3-TR differentiates between short-term insomnia, chronic insomnia, and other insomnia disorder. Changes were made to the criteria for chronic insomnia in this new text revision. The ICSD-3 criteria included that a sleep/wake difficulty is not better explained by another sleep disorder. The text revision clarifies this criteria by stating that the sleep disturbance and daytime symptoms are not due to another sleep disorder, medical condition, mental disorder, or medication/substance use.

All of the following criteria must be met for the diagnosis of short-term insomnia disorder per the ICSD-3-TR:

The diagnostic criteria for chronic insomnia are the same as for short-term insomnia, with the only difference being that the symptoms last for at least 3 months. The diagnosis for other insomnia disorder is only used for individuals who have difficulty initiating and maintaining sleep and do not meet the full criteria for chronic or short-term insomnia disorder.

Prognosis and complications

For many patients with an underlying anxiety disorder, the sleep symptoms may wax and wane, many times preceding and lingering after the mood symptoms. Based on the ICSD-3-TR, the prognosis of insomnia disorder can either be episodic or persistent. The type of sleep complaint (sleep initiation insomnia vs. sleep maintenance insomnia) can also change over time. Short-term insomnia that is caused by a clear inciting event may stop once the trigger has been eliminated. Chronic insomnia, however, can also have an intermittent course, with recurrent episodes that worsen with various life stresses. Complications of persistent insomnia disorder include increased risks for new onset or recurrent depressive and other psychiatric disorders, as well as suicidality. Chronic insomnia also leads to increased risks at work and leads to long-term use of over-the-counter sleep aids. There has also been an increased risk of hypertension in individuals with short objective sleep duration (less than 6 hours).

Individuals with generalized anxiety disorder tend to report that they have felt anxious and nervous for their entire life. The symptoms tend to be chronic, but waxing and waning throughout life. Symptoms appear to be more persistent in low-income countries, but impairment tends to be higher in high-income countries. Rates of full remission are also very low. Children and adolescents with anxiety disorders tend to worry about their performance at school or in sports or other activities. They also tend to worry more about catastrophic events like natural disasters or war.

The course of panic disorder is variable, with 30% to 40% of patients being symptom free, and 10% to 20% continuing to have significant symptoms at long-term follow-up. Good premorbid occupational and social functioning and the presence of a clear precipitating event are good prognostic features.

According to the DSM-5-TR, PTSD can occur at any age, and there is abundant evidence for “delayed expression” of symptoms. The duration and predominance of different symptoms tend to vary over time. Complete recovery can occur within 3 months in around half of adults diagnosed with PTSD, whereas others remain symptomatic for over a year, sometimes for several decades. Symptom recurrence and intensification can occur in response to triggers and life stressors.

Clinical vignette

A 35-year-old woman is referred to the sleep clinic by her psychiatrist with complaints of poor sleep. She has a diagnosis of posttraumatic stress disorder (PTSD) and anxiety disorder and reports a history of difficulty falling and staying asleep ever since a traumatic event 6 years ago. The patient reports that an intruder had broken into her house at night while she was asleep at that time. She describes that, at first, she would be anxious when going to bed and it would take a long time for her to calm herself and then fall asleep. She would also wake frequently at night fearful with a racing heart rate and feelings of impending doom. In addition, she reports frequent nightmares of being chased by an ominous figure. Her difficulties were so frequent and distressing that she started to worry about sleeping in the daytime and actively tried to avoid going to bed. She was seen by psychiatry and was diagnosed with PTSD and panic attacks. She was started on sertraline with improvement in the panic attacks and her other PTSD symptoms, however she continued to have the nightmares and difficulty sleeping. She tried several hypnotics, prior to being seen in the sleep clinic, including trazodone, zolpidem, eszopiclone, and mirtazapine. All these medications helped for a period, but all stopped working past 6 months. She was diagnosed with chronic sleep onset and maintenance insomnia as well as nightmare disorder. She was given several sessions of cognitive behavioral therapy for insomnia as well as low dose gabapentin to help with sleep maintenance and residual anxiety. Treatment of the nightmares consisted of image rehearsal therapy. At her third follow-up appointment 6 months later she reported reduced nighttime awakenings and a reduction in the frequency of her recurrent nightmares. At her 1-year follow up she reported reduction of sleep onset latency to 30 minutes or less most nights and no further nightmares. (In this vignette any resemblance to any persons, real or imagined, is purely coincidental.)

Biological basis

Etiology and pathogenesis

The etiology and pathogenesis of anxiety and trauma-based disorders is not well understood. The hypothalamic-pituitary-adrenal (HPA) axis plays a role in almost all regulatory systems in the body, including mood and sleep. Studies have shown that sleep quality is affected by a change in the HPA axis, which can increase cortisol production, which can disrupt sleep. Sleep deprivation can lead to an increased anxiety state, especially in adolescents (14). This, in turn, increases their risk of developing insomnia. Early adolescents are more vulnerable to the emotional consequences of sleep deprivation, thus worsening the cycle of anxiety and insomnia.

Improvements in neuroimaging has provided more insight into the functional neuroanatomy and neurocircuitry of anxiety-related disorders. The amygdala and insula are key structures involved in processing aversive stimuli and expression of fear and anxiety (43). The medial prefrontal cortex has been shown to be hypoactive in anxiety-related disorders, especially posttraumatic stress disorder (PTSD) and generalized anxiety disorder, whereas the dorsal anterior cingulate cortex has shown increased activities in these disorders (37). This hyperactivity can directly interfere with our normal sleep mechanisms.

The risk of developing PTSD following a traumatic exposure has been demonstrated to be possibly heritable in twin studies and molecular studies (DSM-5-TR). Genome-wide significant loci have also been found to support the theory of heritability. Environmental factors also play a large role in the development of PTSD. In U.S. civilians and veterans, having a lower socioeconomic status, lower education, exposure to prior trauma, childhood adversity, lower intelligence, ethnic or racial discrimination, or a family psychiatric history, all increased an individual’s risk. Another factor that increases the risk of a traumatic event becoming a recurrent stress disorder is the disruption of sleep. Sleep disruption has been found to increase the risk of an event developing into a recurrent stress cycle. Researchers have found that REM sleep promotes the extinction of negative memories and that the disruption of REM sleep may play a role in PTSD (23).

For generalized anxiety disorder, around one-third of the risk of development is from genetic factors. These factors often overlap with the same genetic factors that lead to depression (DSM-5-TR). In generalized anxiety disorder, 19.5% of patients have an affected first-degree relative, compared to 3.5% of control patients (31). Abnormal GABAergic and serotoninergic mechanisms have been documented in patients with anxiety, as well as abnormalities in the regulation of norepinephrine, corticotropin-releasing factor, and neurosteroids (25).

In terms of panic disorder, it is thought that several genes lead to increased vulnerability of developing this; however, the exact genes remain unknown. There is an increased risk of panic disorder in individuals with parents who have anxiety, depression, or bipolar disorders. Having more chronic life stress is also associated with greater panic order severity.

The same activation and hyperarousal of the hypothalamic-pituitary-adrenal axis seen in anxiety and trauma disorders is also seen with individuals suffering from insomnia. Some evidence suggests physiological dysregulation may be more evident in specific subgroups of insomnia, like those with extreme discrepancies in subjective and objective sleep measures. Per the ICSD-3-TR, no discrete structural brain pathology has been identified in most individuals with insomnia.

Sleep problems can also promote substance use, sometimes done to correct the original sleep problem. Cannabis is the most frequently used by patients with posttraumatic stress disorder with the goal of improving sleep (08). However, there is little evidence that shows any objective benefit of cannabis on sleep architecture. Alcohol is also commonly used to initiate sleep; however, it can lead to disrupted sleep, worsening sleep fragmentation, and addiction.

Epidemiology

Anxiety disorders are one of the most common psychiatric disorders. According to the DSM-5-TR, the 12-month prevalence of generalized anxiety disorder is 0.9% among adolescents and 2.9% among adults in the general U.S. population. Onset is usually from teens through late twenties. Females are twice as likely as men to experience generalized anxiety disorder, with around 55% to 60% of individuals with the disorder being women. There are a variety of risk factors for anxiety disorders, including adverse childhood events or parenting practices (like overprotection or overcontrol). Around one-third of the risk of being diagnosed with generalized anxiety disorder is genetic. The prevalence of anxiety disorders decreases with increasing socioeconomic status.

Insomnia has been noted to be a predictor of mood and anxiety disorder onset; therefore, treatment of insomnia is crucial in this population. Severe insomnia was more prevalent in individuals with anxiety disorders (between 24.9% to 45.5%) as compared to those with no disorder (40). Anxiety levels have been shown to be significantly higher in individuals with insomnia.

The DSM-5-TR estimates the prevalence of posttraumatic stress disorder (PTSD) ranges from 6.1% to 8.3%, and the national 12-month prevalence was estimated at 4.7%. Rates of PTSD are higher among veterans and others whose jobs increase their risk of traumatic exposure (for example, police, fire fighters, and emergency medical personnel). The highest rates are found among survivors of rape, military combat, captivity, and ethnically and/or politically motivated internment or genocide (DSM-5-TR). PTSD can occur at any age, though it is less commonly seen in younger age groups given the lower rate of exposure to traumatic experiences. Symptoms begin within the first 3 months of trauma.

Specific and social phobias have a 12-month prevalence estimate of around 8% to 12%. Prevalence rates in the United States and European countries are relatively the same, whereas Asian, African, and Latin American countries tend to have lower rates (around 2% to 4%) (DSM-5-TR). Women are two times as likely to be affected by these disorders than men.

According to the DSM-5-TR, the prevalence of insomnia disorder ranges from 4% to 22% in adults. Insomnia disorder is the most prevalent of all sleep disorders. Around 20% to 40% of individuals at primary care offices seek medical care for their insomnia symptoms (DSM-5-TR). The onset of symptoms can occur at any time during life, but the majority of first episodes occur in young adulthood. New-onset insomnia does increase in prevalence with menopause.

Prevention

There is still limited knowledge and research on the precipitating and predisposing factors that lead to anxiety disorders, thus making it difficult to find preventative measures. Early treatment and education on other comorbid disorders like depression and substance abuse can help to make treatment for anxiety and any sleep-related problems stemming from this more manageable. Some early studies have suggested that improvement in sleep can improve the mental health, specifically anxiety and depression in adolescents (07). This work needs further study but does suggest promise of promoting good sleep results in reduced mood related issues.

Differential diagnosis

The primary differential diagnosis for insomnia disorder with comorbid mental disorder is other causes of insomnia (01). Primary sleep disorders such as restless legs syndrome, periodic limb movement disorder, sleep-related breathing disorders, or circadian rhythm abnormalities may coexist with anxiety disorders and contribute to insomnia. Other medical causes of insomnia may coexist with anxiety disorders, including pain disorders, prostatic hypertrophy, nocturnal asthma, or cardiopulmonary disease. Hyperthyroidism may worsen anxiety and insomnia.

The sleep disturbance of anxiety disorders must also be distinguished from those associated with common comorbid conditions such as substance abuse, inadequate sleep hygiene, or depression (DSM-5-TR). The anxiety arousals in posttraumatic stress disorder and panic disorder must be distinguished from other causes of abrupt arousal such as sleep terrors, sleep choking syndrome, gastroesophageal reflux, sleep apnea, cardiac and pulmonary disorders, and seizures. Sleep terrors present typically in the first half of the night and are a partial arousal from slow wave sleep. Subjects typically have their eyes open but appear somewhat dulled, and are not appropriately responding to the environment. The patients have typically no memory of the events. Sleep choking and reflux can present with sudden difficulty breathing, and the patient may develop anxiousness with the event but not the initial feeling, and patients may note the reflux or acid taste in their mouth. In sleep apnea or orthopnea, patients note the feeling of needing to catch their breath, and again the initial feeling is not one of anxiousness.

Medications used to treat anxiety disorders, such as SSRIs, can result in insomnia, either directly through their activating effects or indirectly through worsening of restless legs syndrome or periodic limb movement disorder.

Diagnostic workup

A thorough sleep history, physical examination, and psychiatric assessment should be performed to fully understand the history and timeline of symptoms. This encounter should also be used to screen for comorbid conditions like poor sleep hygiene, substance use disorders, or other mood disorders. Medical and neurologic conditions that may be associated with underlying anxiety and/or insomnia should also be evaluated at this time. Conditions such as hyperthyroidism and hypoglycemia should be ruled out. Diagnostic tests could be performed to rule out medical causes problems that could cause anxiety like thyroid dysfunction, adrenal dysfunction, hormone imbalance, cardiovascular disease, asthma, or gastrointestinal problems. Medications should be reviewed to ensure these are not contributing to the individual’s symptoms. Other sleep disorders like obstructive sleep apnea and restless leg syndrome should also be evaluated. Although polysomnography is not routinely indicated in initial evaluation, it could be considered if another sleep disorder like obstructive sleep apnea or dream enactment is thought to be present.

Management

The effective treatment of insomnia in the setting of another anxiety or trauma-based disorder depends in large part on effective treatment of the comorbid psychiatric disorder. There are both nonpharmacologic and pharmacologic interventions (13). Cognitive behavioral therapy for insomnia (CBT-I) is a multifaceted treatment for insomnia. CBT-I is currently the first-line treatment as recommended by numerous professional societies, such as the American College of Physicians, the American Academy of Sleep Medicine, and the European Sleep Research Society (12). CBT-I consists of a combination of sleep hygiene, stimulus control, sleep restriction, and relaxation therapy. CBT-I has been shown to improve insomnia severity in long-term follow-up, even when hypnotic treatment has been discontinued. In addition, patients with insomnia report greater acceptance and tolerance of CBT-I versus medications (09). In a large metaanalysis by Hertenstein and colleagues, CBT-I was shown to have a large and significant effect on insomnia severity at first follow-up visit (Hedges’ 0.8, CI 0.4-1.2) (21). This analysis also showed a moderate effect for mental health (Hedges’ 0.7 CI 0.4-0.9) and a significant and large effect on insomnia severity and mental health severity in a PTSD subgroup (09). In a different metaanalysis, looking at the effects of CBT-I on the symptoms of anxiety disorders, only small to moderate effects were seen on anxiety and trauma symptoms (04). Alternatively, approaching the treatment of insomnia and sleep disturbance can also be done by targeting anxiety and trauma using cognitive behavioral therapy for anxiety disorders. Belleville and colleagues found variable effects sizes for improvement in sleep problems depending on the psychiatric disorder (06). There was a large effect size for generalized anxiety disorder (Hedges’ 0.843, CI 0.149–1.536), with moderate to small effects for Parkinson disease with agoraphobia and PTSD (Hedges’ 0.404 CI 95% CI 0.233–0.575 and 0.216 95% CI 0.035–0.398, respectively) (05). However, given the smaller effects on anxiety and trauma symptoms and residual sleep complaints, a combined approach is likely needed in patients with comorbid anxiety and insomnia disorders (04).

Nonpharmacological approaches to generalized anxiety disorder include mindfulness, particularly meditation, in combination with cognitive behavioral therapy. In a study looking at a group exercise intervention, there was improvement in both anxiety and sleep quality as compared to a passive control group (45).

Cognitive behavioral therapy in panic disorder has also been shown to have equivalent effectiveness in panic disorder as compared to medications. The patient is counseled on the knowledge that panic attacks are fleeting and not life-threatening in an attempt to realign false beliefs about the events. Relaxation techniques are taught to reduce the distress that accompany a panic attack. As for specific phobias, exposure therapy is the preferred treatment.

Cognitive behavioral therapy is also beneficial for patients with PTSD. Psychotherapy may also be a helpful component for any anxiety disorders. Targeted psychotherapy has been shown to be helpful in PTSD in improving sleep (44).

Pharmacologic therapy is also a component of treatment for anxiety disorders. Guidelines recommend the use of SSRIs, such as escitalopram, sertraline, and paroxetine, and these should be used as first-line pharmacologic treatments (38). The SNRIs venlafaxine and duloxetine are also used, as well as tricyclics. Panic disorders respond well to SSRI treatment, but it should be noted that anxiety symptoms can increase temporarily at the outset of treatment with SSRIs. Both SSRIs and SNRIs are effective in PTSD. Prazosin has been shown to improve sleep quality and reduce nightmare frequency in a study of combat veterans (36). However, a randomized control trial in combat-related PTSD did not show improvement in sleep quality or nightmare frequency (35). In a large randomized control trial, the combination of 3 mg of eszopiclone and 10 mg of escitalopram in patients with generalized anxiety disorder was shown to improve anxiety symptoms after 8 weeks more than escitalopram in combination with placebo (32). The alpha-2 delta ligand medications, gabapentin and pregabalin, have also been used in the treatment of anxiety and insomnia. The gabapentinoids increase slow wave sleep, as opposed to benzodiazepines and the benzodiazepine receptor agonists. Several randomized control trials have shown that the use of pregabalin at 150 to 600 mg/day for 4 to 8 weeks has been shown to reduce anxiety scores in patients with generalized anxiety disorder. In addition, patients with generalized anxiety disorder that is unresponsive to SSRI or SNRI monotherapy may also respond to pregabalin in the treatment regimen (09).

In all patients, good sleep hygiene techniques should be taught with a thorough sleep history. Particular attention should be made to avoid substances that can worsen sleep quality and increase anxiety, such as caffeine. In addition, comorbid sleep apnea should also be treated. A decreased response to cognitive therapy and increased PTSD severity is noted in patients with obstructive sleep apnea (29).

Special considerations

Pregnancy

Around 35% of pregnant women are diagnosed with an anxiety disorder (33). Around 15% to 20% of women either continue to have an anxiety disorder or are diagnosed with one in the postpartum period (18). The perinatal period often features specific fear, worry, and anxiety concerning the pregnancy itself and its outcomes, often referred to as pregnancy-related anxiety (20). It has been associated with negative maternal and child health outcomes throughout gestation, birth, and early childhood. This includes increased maternal mortality, preterm labor, impaired cognitive function in the children, low birth weight, poor bonding, and poor development and health in the child overall.