Clinical manifestations

Presentation and course

	• A nightmare is a frightening dream that usually awakens the sleeper.
	• Nightmares in children subside with aging but if untreated may persist in adulthood as chronic nightmares.

The International Classification of Sleep Disorders: Diagnostic and Coding Manual classifies nightmares as one of the REM sleep parasomnias (04). A nightmare is an intense frightening dream that causes an awakening. Often on awakening, the person is still frightened because of the intensity of the perception. Nightmares are distinguished from other parasomnias, such as REM sleep behavior disorder and NREM-related parasomnias such as disorders of arousal from NREM sleep and sleep terrors.

Important diagnostic criteria of nightmares based on DSM V (05) are as follows:

	• Repeated awakenings during the second half of the sleep period with ability to recall frightening dreams. Rapid return of alertness on awakening from the frightening dreams.
	• Sleep disturbance resulting from the awakening causes impairment in social, occupational, or other important areas of functioning.
	• Nightmares do not occur exclusively during the course of another mental disorder, such as delirium or a general medical condition.
	• Nightmares are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication).
	• The last DSM V diagnostic criterion is problematic. There is no such thing as a “physiological” effect of a medication, rather it is “pharmacological”. There is a large list of drugs associated with nightmares.

There is no requirement of difficulty with respiration, which is more likely to be a characteristic of sleep apnea. There is no confusion and disorientation, which are more common following sleep terror attacks. The distinctive features of a nightmare are the recollection of a long, frightening dream and clear orientation on awakening.

Prognosis and complications

Although most children who suffer from nightmares experience a decrease in their frequency to about one per year as adults, the 3% who are chronic sufferers have lifelong, frequent episodes if untreated.

Nightmares are associated with suicidal behavior independent of other risk factors for suicide, such as depression, anxiety, and posttraumatic stress disorder (48). A study was able to show that 80% of patients with a suicidal crisis started having bad dreams four months and nightmares three months before the crisis, which offers an opportunity to screen, predict, and detect suicidal behavior early (15).

Clinical vignette

The patient was a 40-year-old recently married woman who consulted the Sleep Service because her frequent awakenings from nightmares were interfering with her sleep and her marriage. She reported that they began following a rape when she was 21 years of age. She awoke four to five times nightly, often with profuse diaphoresis. The theme of the dreams dealt with an attack by a man of "pure evil" who was threatening her life. Therapeutic instructions taught her to control the situation in her dreams rather than aborting them when she became aware of her terror. Within five sessions the patient learned to fight back, outwit, or leave that dream scene for another without waking. At that point, the nightmares ceased.

The association between nightmares and suicide is complicated, and the research shows mixed results. For instance, nightmares were connected with suicidal behavior independent of other risk factors for suicide, such as depression, anxiety, and posttraumatic stress disorder (48). Furthermore, a one-year prospective study of 6923 Chinese adolescents has shown that suicidal risk and behavior (suicidal thought, planning, and attempt) increased with increased nightmare frequency and distress (24). On the other hand, in a prospective cohort study comprising of 40,902 patients and a follow up of 19 years, the researchers found no evidence suggesting that nightmares increase suicide rates (19).

Biological basis

Etiology and pathogenesis

	• Genetic and environmental factors are involved in the pathogenesis of nightmares.
	• There is a strong relationship between nightmare frequency and psychiatric disorders.
	• Nightmares as symptoms of PTSD are critical because sleep disruption may lead to maintenance of PTSD in a vicious circle.
	• Nightmares may occur as side effects of medications.

Various studies suggest that some genetic factors, in addition to unrelated environmental effects, are involved in the pathogenesis of nightmares. There is also a strong relationship between nightmare frequency and psychiatric disorders.

Pathophysiology of nightmares is not clear but several hypotheses to account for nightmares have been proposed in the past. These include suggestions that nightmares are dreams that stimulate threatening events as a rehearsal for survival and that nightmares perform an integrative function by which dreams following a traumatic experience are woven into memory.

According to the stress acceleration hypothesis, adverse childhood experiences have a deleterious impact on future physical and mental health, increasing risk for psychiatric problems, sleep disorders, and idiopathic nightmares (32). The proposed mechanisms are disruption of normal infantile amnesia, which enables early childhood memories to influence later emotions including the expression of threats in nightmares, and alterations of regulation of fear extinction during REM sleep leading to nightmares. Findings of a sleep-lab study on participants with frequent nightmares indicate that they had increased high-frequency spectral power during NREM and pre-REM periods, as well as relatively reduced slow frequency and increased fast frequency spectral power across pre- and post-REM periods as compared with healthy controls (08). This combination of reduced sleep-protective activity and increased hyperarousal suggests an imbalance between sleep regulatory and wake-promoting systems in participants with frequent nightmares. Findings of another study do not support the concept that abnormal REM sleep plays a role in the pathophysiology of frequent nightmares; rather, the altered REM sleep in nightmare disorder could have been confounded with comorbid pathologies (50). Furthermore, it is suggested that there is altered autonomic activity (parasympathetic) during sleep among nightmare recallers. A study has shown a significant difference in heart rate of nightmare recallers compared to healthy control subjects that occurs only during the sleep and not during restful wakefulness (49).

Various disorders associated with nightmares include the following:

• Advanced cancer • Hemodialysis for renal cancer • Hypoglycemia resulting from insulin treatment of type 1 diabetes in childhood • Psychiatric disorders, eg, schizophrenia • Drug-induced neurologic disorders • Sleep apnea • Parkinson disease • Posttraumatic stress disorder • Temporal lobe epilepsy

Psychopathology and nightmares. There appear to be personality characteristics in adults contributing to vulnerability to frequent nightmares. Half of those afflicted meet criteria for schizotypic personality, borderline personality, or schizophrenia. The remaining 50% may be artistic or creative individuals who share with those who have more psychopathology the characteristic of being unusual thinkers. Although nightmares have been reported in children with autism, the frequency is less than in other sleep disorders.

In a prospective study following more than 40,000 patients for 19 years, it was shown that the frequency of nightmares was strongly correlated with self-reported depressive and anxiety symptoms and was strongly associated with psychopathology, whereby nightmares were more frequent in patients with mood and anxiety disorders (19).

The person with nightmares is more likely to have a history of mental illness and to show an increase in nightmares prior to the onset of psychotic episodes. In patients with major depression, those reporting frequent nightmares, especially women, have higher suicide potential than those who do not. Insomnia and nightmares independently and additively aggravate depression (31). Increased nightmare frequency in patients with borderline personality disorder is not determined by comorbid depression or posttraumatic stress disorder (42).

Based on the hypothesis that disturbed dreaming is associated with impaired prefrontal and fronto-limbic functioning during sleep, a study of performance in various neuropsychological tasks has reported impaired executive functions in subjects with frequent nightmares.

EEG and autonomic alterations in persons with frequent nightmares. Although nightmares do not have any significant neurologic sequelae, abnormal arousal processes and wake-like alpha activity during sleep have been reported as pathophysiological features (45). Thus, sleep is compromised during transitions between REM and non-REM, but it is stabilized in the post-REM periods. The authors of this study propose that these phenomena might indicate altered emotional processing in subjects with nightmares. The belief that impaired self-reported sleep quality by sufferers of nightmares is caused by an autonomic response rather than altered sleep pattern is supported by an ambulatory polysomnographic study that demonstrated that nightmares are accompanied by increased autonomic activation (36).

Drug-induced nightmares. Nightmares may occur as side effects of medications listed in Table 1.

Table 1. Drugs Associated with Nightmares

Antidepressants
	• Selective serotonin reuptake inhibitors
		- Fluoxetine - Paroxetine - Mirtazapine - Venlafaxine
	• Tricyclic antidepressants • Monoamine-oxidase inhibitors
Analgesics
	• Nonsteroidal anti-inflammatory drugs:
		- Naproxen
	• Nonopiate analgesics:
		- Ketamine
	• Opioids
Antianxiety agent: bupropion Antibiotics
	• Erythromycin • Fluoroquinolone
		- Fleroxacin - Ciprofloxacin
	• Antivirals
		- Efavirenz for treatment of HIV - Ganciclovir
Antiepileptics
		- Lamotrigine - Valproic acid
Antiparkinsonian drugs
	• Amantadine • Cabergoline • Levodopa • Selegiline
Antipsychotics
	• Chlorpromazine • Thiothixene
Cardiovascular drugs
	• ACE-inhibitor: captopril • Angiotensin receptor blocker: valsartan, antihypertensive • Beta-blockers: propranolol • Calcium channel blocker: verapamil • Digoxin • Ivabradine for treatment of coronary heart disease • Statins: atorvastatin for lowering cholesterol
Corticosteroids, high dose CNS stimulants
	• Amphetamine • Methylphenidate • Phenmetrazine
Drugs for Alzheimer disease
	• Donepezil, cholinesterase inhibitors • Galantamine • Memantine
Hypnotics/Sedatives
	• Barbiturates, short-acting • Benzodiazepines: nitrazepam
Miscellaneous drugs
	• Alpha-agonists • Flutamide • Mefloquine • Oxybutynin • Procarbazine • Rauwolfia alkaloids • Varenicline for smoking cessation
Withdrawal of drugs
	• Alcohol withdrawal • Benzodiazepine withdrawal • Hypnotic withdrawal

Withdrawal of REM sleep-suppressing medications such as the tricyclic antidepressants and the monoamine oxidase inhibitors, as well as withdrawal from alcohol, barbiturates, or tranquilizers is also followed by an increase in disturbed dreaming and nightmares. Nightmares have been reported with mirtazapine, a novel tetracyclic antidepressant that enhances noradrenergic and serotonergic transmission by blocking central alpha2-adrenergicreceptors and does not suppress REM sleep (10; 29). The nightmares reported disappeared following discontinuation of mirtazapine. Clonidine, an α-2 adrenergic agonist, which was used to treat nightmares induced by bupropion, an antidepressant, is a norepinephrine dopamine reuptake inhibitor (27).

Nightmares have been reported following use of drugs for Alzheimer disease, such as donepezil and memantine. Galantamine-associated nightmares are an uncommon adverse event and may be exacerbated by rapid titration (11).

Nightmares have been reported as a side effect of valsartan, an angiotensin receptor blocker used for treating hypertension. Ivabradine, a heart rate lowering agent used for treatment of angina pectoris, has been associated with nightmares. Water-soluble beta-blockers such as atenolol are less likely to cause nightmares as they do not easily cross the blood-brain barrier.

Parkinson disease and nightmares. Nightmares are more common in Parkinson disease patients than in the general population.

Sleep apnea and nightmares. No studies have proven that hypoxia causes nightmares. In a sleep laboratory study, patients with higher apnea-hypopnea index indicating severe obstructive sleep apnea reported a lower nightmare frequency, suggesting that significant sleep apnea suppresses nightmare recall. Decreased nightmare recall may be secondary to REM sleep suppression that is common in patients with significant sleep apnea (07).

Epilepsy and nightmares. Sleep disturbances are known to be associated with temporal lobe epilepsy. Although there are case reports of nightmares in epileptic patients, a prospective study in unselected epilepsy patients showed that the incidence of nightmares was 6% compared to 16% in controls without epilepsy.

Posttraumatic stress disorder and nightmares and sleep. Nightmares as symptoms of PTSD are critical because sleep disruption may lead to maintenance of PTSD in a vicious circle. Moreover, successful treatment of chronic nightmares with cognitive behavioral therapy reduces symptoms of PTSD. A study has evaluated both posttraumatic stress disorder-specific and insomnia-specific factors to predict sleep quality, efficiency, and nightmares in persons with posttraumatic stress disorder (44). The conclusions were that both sleep- and posttraumatic stress disorder-related factors play a role in maintaining insomnia among those with posttraumatic stress disorder, whereas nightmares seem to be linked more closely with only posttraumatic stress disorder-related factors.

Polysomnographic studies show that nightmares are related to altered sleep architecture with impaired sleep continuity and emotion-related increase in REM sleep duration. It has also been suggested that any change in receptor sensitivity that results in longer REM sleep episodes with increased eye movements will be likely to result in more nightmares.

Epidemiology

	• Nightmares are common in young children and may persist in adulthood.
	• Nightmares are more frequent in PTSD.

Nightmares occur in approximately 4% of the adult population at least on a weekly basis (46). In a large-scale epidemiologic study in Hong Kong, overall nightmare prevalence was 16.3%. Among females, nightmares occurred in 20.4% of respondents compared to only 12.1% of males (52). Nightmares are common in young children. A study of 190 school children in the Netherlands aged 4 to 12 years reported the “scary dream” frequency at 80.5%, with a peak in children 7 to 9 years of age. Most of the studies agree that the frequency of nightmares decreases with age and an increasing sense of competence. For some people, however, nightmares persist as a lifelong chronic problem.

Nightmares are difficult to study in the laboratory, as they rarely occur under conditions in which the patient feels increased safety. Infrequent nightmares are common, but the adult prevalence depends heavily on the method used to elicit the data. In most of the studies, nightmares are reported to occur more frequently in females than in males. It has been shown that around 1 in 20 members of the general population experience nightmares at least once a week (40). In this study, frequent nightmares were associated with comorbid sleep and psychiatric disorders but were also independently related to neurotic personality traits, irrespective of psychiatric diagnosis.

The role of stress has been studied following natural disasters, exposure to war, and personal traumas. Forty percent of college students living in the San Francisco Bay Area at the time of the 1989 earthquake reported nightmares in comparison to only 5% of students in Arizona. When 3.1 million men and women who served in Vietnam were surveyed for nightmare frequency, combat exposure was strongly correlated. Frequent nightmares were found exclusively in those with a current diagnosis of posttraumatic stress disorder (15%). Another way life events can affect dreams is demonstrated by the rise of frequency of unpleasant dreams, nightmares, and dream recall during the Covid-19 pandemic (01).

Among college students, childhood traumatic experiences are more frequent in nightmare sufferers than in those who did not have nightmares. In a German study, traumatized children and adolescents reported an average of 9.7 nightmares per month compared to 1.7 in nontraumatized participants (33).

A high percentage of burn survivors report frequent nightmares and this has been used as a screening tool for posttraumatic stress disorder. Nightmares are reported in 25% of patients undergoing hemodialysis for renal failure. Nightmares are more common in those undergoing major surgery than in those with minor elective surgery. Despite frequent association, there is no adequate explanation for the range of dreams following trauma, including the posttraumatic nightmares of posttraumatic stress disorder that are both symbolic and repetitive. Nightmares are more common among Northern Plains American Indian war veterans than other veteran populations: 97% of veterans with posttraumatic stress disorder report nightmares, which may have cultural implications.

Results of a population-based cohort study indicate that psychological and demographic factors are associated with nightmares in the elderly and the prevalence of nightmares increases after age 70, which suggests the need for further studies of nightmares in the elderly (35).

Prevention

No method of prevention is known. Awareness of withdrawal along with the effects of some medications in vulnerable people should be noted, as should the need to avoid sleep deprivation, as it is followed by an increase in the length and activity of REM episodes.

Differential diagnosis

Confusing conditions

Sleep terrors. These involve fearful arousal from stage N3 of sleep early in the night, usually within the 1st hour. Dream content is reported only rarely in sleep terrors; the person is often confused and inconsolable and may be physically active but amnestic for the event. Respiratory rate and heart rate may double.

Posttraumatic stress disorder. The fearful awakenings of those diagnosed with posttraumatic stress disorder occur earlier in sleep than those with lifelong nightmares and may be either from REM sleep or stage 2 sleep. The dream content tends to be more realistic and is often a repetition of actual traumatic events.

REM sleep behavior disorder. This involves a confusional state on arousal from a REM period that lacks the usual atonia and so may involve fight or flight behaviors that enact dream content.

Disturbance of dreaming. This is characterized by vivid, unpleasant dreams that are usually completed rather than interrupted, involving negative effects of a wider range than fear (namely frustration, sadness, and anger), with good recall and without physiologic activation.

Awakenings with sleep apnea. Feelings of suffocation and fear due to sleep apnea are usually without dream content and may occur from any stage of sleep, often when the patient is sleeping supine.

Drugs. Use of medication or drug withdrawal reported to be associated with nightmares should be considered in differential diagnosis.

Diagnostic workup

• Home log of dream reports

A 2-week home log of dream reports noting the time of night that the awakenings occur often is helpful. A careful sleep history that focuses on the time of night of fearful awakenings helps to distinguish REM sleep-related nightmares from stage N3 sleep terrors. The availability of detailed dream reports and the absence of confusion on awakening help to make this distinction. Polysomnography is indicated if concurrent sleep apnea or REM sleep behavior disorder is suspected. Nightmare patients show long, frequently interrupted REM-sleep periods with high rates of rapid eye movements.

Management

	• Nonpharmacologic, such as cognitive-behavioral therapy
	• Pharmacologic, such as prazosin
	• Combination of pharmacologic and nonpharmacologic methods

Nonpharmacologic. A good deal of work has been done to develop behavioral or psychological treatment programs for sufferers of both posttraumatic stress disorder (PTSD) and chronic nightmares. Most studies are based on only a few cases and are without controls. Among these are reports on the usefulness of hypnosis, rehearsal of masterful endings of the dreams, and eye-movement desensitization.

At the forefront of nonpharmacologic treatments and a level A treatment for nightmares is image rehearsal therapy (IRT), which is an evidence-based cognitive behavioral therapy designed to reduce nightmares by helping the patient to alter their nightmares by creating different endings to the nightmares and rehearsing them (03; 54).

A controlled trial of combined cognitive-behavioral therapy for insomnia and imagery rehearsal therapy for nightmares was shown to improve sleep as well as posttraumatic stress disorder symptoms in Afghanistan and Iraq veterans (26). In fact, among all possible treatments of nightmares for patients suffering from posttraumatic stress disorder, the treatments that involved imagery rescripting proved to be the most effective (03).

A study using imagery rehearsal for U.S. Vietnam war veterans with severe, chronic posttraumatic stress disorder and fairly replicative nightmares showed that this method may be most effective when the rescripted dream incorporates a resolution of the nightmare theme and excludes violent details. Imagery rehearsal studies do not clarify if the alleviation of nightmares is primarily due to becoming aware of the dream when it occurs or to the ability to alter some aspect of it. Preliminary results of a 6-month follow-up of imagery rescripting intervention in posttraumatic stress disorder provide evidence that trauma-related cognitions may improve with time as a result of imagery rescripting, which is an explanation for reduction of posttraumatic nightmares. In addition, combining imagery rehearsal therapy with targeted memory reactivation was shown to be more effective than imagery rehearsal therapy alone in reducing nightmare frequency (43). Cognitive behavioral treatment may be considered as a first-line therapy for trauma-exposed individuals with chronic nightmares, depression, and posttraumatic stress disorder. In a systematic review, it was shown that cognitive behavior therapy for insomnia (CBT-I) alone or combined with image rehearsal therapy or rescripting therapy for nightmares (ERRT, which will be discussed later in the chapter) was shown to be effective in reducing nightmare frequency. It usually takes an average of six to eight sessions to reduce insomnia and nightmares (20).

A review of pharmacologic and nonpharmacologic treatments since 2010 shows that pharmacologically, prazosin has shown robust clinical effects with minimal side effects, whereas psychologically, imagery rehearsal therapy commands the greater portion of nightmare literature due to its established efficacy. The results of a metaanalysis of the effectiveness of treatments for chronic nightmares using imaginal confrontation with nightmare contents, or imagery rescripting and rehearsal, indicate that a higher duration of time for the former is associated with greater improvements; however, dismantling studies are required to draw conclusions as to which of the two methods is more effective (17). A critical review of controlled as well as uncontrolled trials of imagery rehearsal for posttraumatic nightmares has pointed out poor methodology and unsubstantiated conclusions (18). This review points out the need for randomized controlled trials of imagery rehearsal with reliable comparison conditions and predictors of dropout and outcome, as well as dismantling studies of rehearsal treatment. A randomized trial has shown that image reversal therapy is an effective treatment for nightmares in patients with comorbid psychiatric disorders and can be employed in addition to the ongoing treatment (51). Although imagery rescripting and imaginal exposure are both treatments for nightmare disorder, the underlying mechanisms of action are different, and these were investigated in a randomized waitlist-controlled trial (23). The results showed that therapeutic efficacy of imagery rescripting was mediated by enhanced mastery of the nightmare content, whereas treatment effects of imaginal exposure were mediated by increased tolerability of the negative emotions elicited by nightmares. A single-blinded, randomized-controlled study has shown that both image rescripting and imaginal exposure were successful in reducing nightmare distress, frequency, effects, and psychopathology among all patient demographics and disorder characteristics (41).

Lucid dreaming is another nonpharmacological method that is emerging as a potential treatment for nightmares. Lucid dreaming, commonly known as LD, refers to the state where a person is consciously aware that they are dreaming, it can be described as any technique aimed at promoting awareness and control within dreams for therapeutic reasons. In a systematic review, lucid dreaming was shown to reduce nightmare frequency by up to 50% with lasting effects after a handful of sessions (34).

Pharmacologic.

Benzodiazepine. The nightmares of patients with REM sleep behavior disorder have been treated with small nighttime doses of the benzodiazepine clonazepam, which has a muscle relaxant effect that protects the sleeper from acting out the dreams. Clonazepam, however, is ineffective in improving sleep disturbances, particularly nightmares, associated with combat-related posttraumatic stress disorder.

Antidepressants. Trazodone is an antidepressant medication commonly prescribed for nightmares in posttraumatic stress disorder due to its low abuse potential. It has been shown to reduce frequency of nightmares in veterans from 3.3 nights to 1.3 nights in 72% of participants. In 19% of participants in a study, trazodone was discontinued due to side effects such as priapism, dry mouth, and sedation (12). In addition, it may be of special use in patients with a comorbid alcohol abuse disorder where the use of benzodiazepines should be avoided. However, there is a lack of controlled trials cementing the place of trazodone in the treatment of nightmares (14).

One adverse effect of this therapy is higher than expected occurrence of priapism.

Antiepileptics. Gabapentin, an anticonvulsant prescribed to facilitate sleep in patients with posttraumatic stress disorder, may result in a decrease in the frequency of nightmares. Topiramate, an antiepileptic, is also useful for nightmares associated with PTSD.

Antipsychotics. The atypical antipsychotic medications have been shown to reduce nightmares in small pilot studies of patients with acute posttraumatic stress disorder; however, none have been FDA approved for that purpose (12). Risperidone, which acts as a serotonin-dopamine and noradrenergic receptor antagonist, has been shown in one retrospective chart review to stop nightmares in 43% and reduce the frequency and intensity of nightmares in 85% of patients suffering from posttraumatic nightmares (14). These findings led to a pilot open-label, flexible-dose trial that showed a significant reduction in trauma-related dreams and nightmares in combat veterans suffering from posttraumatic stress disorder and post-trauma nightmares. There is a need, however, for clinical trials in order to recommend risperidone in the treatment of nightmares.

Cannabinoids. The cannabinoids, delta9-tetrahydrocannabinol and its analog, nabilone, can reliably attenuate the intensity and frequency of post-traumatic nightmares (28). Nabilone has been shown through several studies including a randomized controlled study and systematic reviews to be a potential promising treatment of patients with nightmares, whereby it has led to a reduction or complete resolution of nightmares in a majority of patients. However, those studies have limitations mainly due to the small sample sizes and poor quality of the study designs. Hence, there is a need for further studies investigating nabilone in order to recommend it as a primary treatment (14).

Clonidine. Clonidine is an α2-adrenergic agonist used for treatment of hypertension, attention deficit hyperactivity disorder, and drug withdrawals, among others. A retrospective study done in veterans suffering from posttraumatic stress disorder has shown that low-dose clonidine is promising as an effective treatment for posttraumatic stress disorder and nightmares with 50% to 60% of patients, showing at least partial improvement for nightmare symptoms (09). There is still a need, however, for a randomized controlled trial to further study the role of the drug in the treatment of nightmares.

Prazosin. Prazosin remains the most researched treatment for nightmares and is the preferred first-line therapy when deemed necessary (14; 54). In 2010, prazosin was recommended as a level A treatment by the American Academy of Sleep Medicine but was downgraded due to a single trial in 2018 (30). The evidence regarding prazosin remains controversial, with several published metaanalyses of randomized controlled studies of prazosin that reinforce it as a level A treatment for nightmares (53). It is a centrally active alpha1-adrenergic antagonist prazosin has been proposed as a treatment. Prazosin may decrease the arousal produced by norepinephrine in response to a stressor. A combined review of four open-label studies, one retrospective chart review, and two placebo-controlled trials of prazosin for nightmares related to posttraumatic stress disorder show that it is a promising and fairly well-tolerated agent for the management of posttraumatic stress disorder-related nightmares and sleep disturbances.

Blood pressure should be monitored as orthostatic hypotension may occur early in therapy with prazosin. However, a randomized controlled trial of prazosin for nightmares related to PTSD in soldiers returning from active duty in Iraq and Afghanistan showed that it was effective and well tolerated with no differences in blood pressure between the treated and control groups (39).

Most of the reported studies of use of prazosin for nightmares associated with PTSD are in adults, but use of prazosin has now been extended to prepubertal children with nightmares resulting from PTSD (37). According to a retrospective chart review of children with posttraumatic stress disorder, treatment with prazosin was well-tolerated and associated with improvement in nightmares (22). Case reports, reviews and retrospective systematic analysis of data on 18 patients suggest that prazosin is well-tolerated and associated with improvement in symptoms associated with pediatric PTSD including nightmares (13).

A systematic review of clinical trials found that results were mixed for the randomized trials, but reduced nightmare severity with use of prazosin was consistently reported in the open-label trials, retrospective chart reviews, and single case reports. Another systematic review of randomized, controlled trials has shown that prazosin reduces both frequency and severity of nightmares in patients who meet diagnostic criteria for posttraumatic stress disorder (02). A metaanalysis of randomized trials of prazosin versus placebo to assess safety and efficacy for treatment of PTSD-related nightmares, sleep disturbances, and overall illness severity showed a significant response to treatment with prazosin (16). Prazosin was well tolerated and had no significant sustained effect on blood pressure if dose was carefully titrated. In a 26-week placebo-controlled randomized trial on military veterans who had chronic posttraumatic stress disorder, prazosin did not alleviate nightmares (38). Because previous studies have shown benefit of prazosin, the authors of the trial suggest further studies with more refined characterization of autonomic nervous system activity and nocturnal behaviors are needed to determine whether there may be subgroups of veterans with posttraumatic stress disorder who can benefit from prazosin. Biomarkers of response to prazosin are required for personalization of prazosin therapy of nightmares due to posttraumatic stress disorder.

Combination of pharmacologic and behavioral treatments. The increased interest in treatment of nightmares suggests that the outlook is good for the development of more aggressive and effective management programs. A review of the emerging evidence leads to the suggestion that management of posttraumatic stress disorder-related sleep disturbances may be improved by conducting combined behavioral treatments, or pharmacological treatments, or both, rather than considering sleep symptoms in isolation. A metaanalysis concluded that there are both psychological and pharmacological interventions that have documented effects for the treatment of nightmares, but minimal interventions were less effective than studies offering more extensive interventions (06).

One approach is the trauma-focused, integrative psychotherapy called eye movement desensitization and reprocessing (EMDR) where the primary aim is to process traumatic memories that underlie several mental disorders. EMDR was used in addition to antidepressant venlafaxine to manage a young patient with acute stress disorder following polytrauma and recurrent nightmares leading to cessation of nightmares, relief of anxiety, and prevention of PTSD (47).

An emerging combination therapy consists of memory reconsolidation impairment via the usage of propranolol, which is a b-adrenergic receptor blocker. This method consists of multiple sessions of psychotherapy whereby the patient is re-exposed to the traumatic memory 60 minutes after taking propranolol. The memory is deemed to be labile in the reactivated state, meanwhile propranolol reduces hyperarousal via noradrenergic blockade and, thus, dissociates bad emotions from the reconsolidated traumatic memory. Several previous studies including a preliminary one have shown the therapy to be well tolerated and superior to placebo in reducing posttraumatic stress disorder-related nightmares (25). There is a pressing need, however, for a randomized controlled study in order to further study the effects of this treatment.

Clinical trials of therapies for nightmares. As of June of 2023, 15 active clinical trials are listed under the topic “nightmare” on the U.S. government website (http://www.clinicaltrials.gov). Most of the active clinical trials are in patients with posttraumatic stress disorder. Some of the completed trials with published results have been cited in this article under various methods of treatment. A sampling of some active ongoing include:

• A phase 2 trial of exposure, relaxation, and rescripting therapy (ERRT) as a promising psychological intervention developed to target trauma-related nightmares and sleep disturbances. Although further evidence is needed, ERRT has already been shown to reduce the number and intensity of nightmares, as well as improving overall sleep quality in both civilian and veteran subjects. This study will assess the efficacy in individuals diagnosed with bipolar disorder (NCT02242110).

• A pilot study to estimate safety and efficacy of the NightWare digital therapeutic system (iPhone + Apple watch + proprietary application) for the treatment of nightmare disorder associated with posttraumatic stress disorder (PTSD)-related sleep disturbance and the impact of improved sleep with the NightWare digital therapeutic system (NCT04040387).

Special considerations

Pregnancy

The frequent occurrence of dream-associated behaviors including nightmares during pregnancy and the postpartum period may reflect the emotional influence of maternal concerns or changes caused by severe sleep disruption, REM sleep deprivation, and/or altered hormone levels. Posttraumatic stress disorder, including its manifestation as nightmares, is more prevalent in perinatal than general population of women.

Anesthesia

Postoperative nightmares are common and likely related to the seriousness of the surgery. Nightmares can be expected to increase, especially in patients who are subject to chronic nightmares.