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Rapid eye movement sleep behavior disorder

Rapid eye movement sleep behavior disorder
Authors:
Michael Howell, MD
Carlos H Schenck, MD
Section Editor:
Alon Y Avidan, MD, MPH
Deputy Editor:
April F Eichler, MD, MPH
Literature review current through: May 2025. | This topic last updated: Jun 27, 2025.

INTRODUCTION — 

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. Dream enactment ranges in severity from benign hand gestures to violent thrashing, punching, and kicking. Patients typically present to medical attention with a concern related to injurious or potentially injurious actions to themselves and/or their bed partner.

In spontaneously occurring cases, RBD is a prodromal syndrome of alpha-synuclein neurodegeneration. Thus, the vast majority of RBD patients will eventually demonstrate signs and symptoms of Parkinson disease (PD), dementia with Lewy Bodies (DLB), or a related disorder (eg, multiple system atrophy [MSA]), often after a prolonged interval. Prior to the emergence of a parkinsonian syndrome, patients often have subtle motor and cognitive deficits, as well as hyposmia (poor sense of smell) and constipation, consistent with an impending neurologic disorder.

This topic will review the clinical features, evaluation, and management of RBD in adults. An approach to abnormal movements and behaviors during sleep and other specific parasomnias in adults are discussed separately. (See "Approach to abnormal movements and behaviors during sleep" and "Disorders of arousal from non-rapid eye movement sleep in adults" and "Nightmares and nightmare disorder in adults".)

PREVALENCE AND RISK FACTORS — 

The prevalence of rapid eye movement (REM) sleep behavior disorder (RBD) varies depending on the population studied.

●Adult population – The prevalence of RBD in the general adult population when confirmed with polysomnography (PSG) ranges from 0.5 to 1.5 percent and rises to approximately 2 percent in older adults [1-7]. These values are likely an underestimate, as many cases of RBD are unreported and unrecognized [5,8].

●Pediatric population – RBD is rare in children and usually associated with childhood narcolepsy, neurodevelopmental disorders, and use of certain medications. (See "Parasomnias of childhood, including sleepwalking", section on 'Rapid eye movement sleep behavior disorder'.)

Major risk factors for RBD include the following:

●Male sex – In the older adult population, RBD has a strong male predominance (as high as 9:1 male to female ratio), but female cases are likely underreported and underdiagnosed [2]. Much of the discrepancy may be due to detection bias, since males often have more aggressive and violent RBD episodes compared with females [2,9].

Compared with males, females with RBD are typically younger and more likely to have exposure to serotonergic antidepressants [10].

●Age – The prevalence of RBD is highest among older adults, largely due to the cooccurrence of neurodegenerative disorders.

●Neurodegenerative disorders – RBD is highly prevalent among patients with alpha-synuclein neurodegenerative disorders including Parkinson disease (PD; 33 to 50 percent), multiple system atrophy (MSA; 80 to 95 percent), and dementia with Lewy bodies (DLB; 80 percent) [11-16]. (See 'Alpha-synuclein neurodegeneration' below.)

●Narcolepsy – Approximately 50 percent of patients with narcolepsy type 1 have RBD. (See 'Narcolepsy and orexin deficiency' below.)

●Serotonergic antidepressant use – The dream enactment of RBD frequently emerges or is exacerbated by medications (table 1), most commonly the serotonergic antidepressants. (See 'Medications' below.)

●Others – Other risk factors for RBD include traumatic brain injury, posttraumatic stress disorder (PTSD), and neurologic disorders other than alpha-synuclein degeneration. (See 'Other neurologic disorders' below.)

PATHOGENESIS — 

The pathophysiologic basis of rapid eye movement (REM) sleep behavior disorder (RBD) involves degeneration or dysfunction of the brainstem circuits responsible for maintaining muscle atonia (paralysis) during REM sleep (figure 1).

REM atonia confers a protective measure, preventing people from physically manifesting dream mentation. Quiescence of motor activity during REM sleep may also facilitate sleep-related memory consolidation.

The physiologic suppression of motor activity during REM sleep is the cumulative result of multiple neuronal circuits that predominantly originate in the lower brainstem and ultimately terminate on spinal cord motor neurons. Key regions involved in the generation of REM atonia are the subcoeruleus nucleus and the ventral medulla [17].

In narcolepsy type 1, orexin-mediated hypothalamic pathology is implicated in the failure to suppress REM sleep-related motor activity [18]. Orexin, secreted from the lateral hypothalamus, promotes state (ie, wake, non-REM [NREM], REM) stability and prevents frequent transitioning between states. Orexin deficiency associated with narcolepsy type 1 leads to REM-wake instability, which promotes wake-like motor activity in parallel with REM dream mentation [19-21]. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Etiology and pathophysiology'.)

ETIOLOGY — 

Rapid eye movement (REM) sleep behavior disorder (RBD) is the clinical manifestation of a variety of central nervous system pathologies and medication side effects, all of which result in a failure of brainstem circuitry to inhibit spinal motoneurons during REM sleep.

Alpha-synuclein neurodegeneration — Alpha-synuclein pathology—as seen in Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA)—is the most common cause of RBD. In the absence of provoking medication or comorbid neurodegenerative disorder, it is the presumed cause of all cases of isolated RBD (previously referred to as idiopathic RBD) [22].

The pontine and medullary nuclei that control REM sleep are early targets in the natural history of synucleinopathies [11,23]. This pathology gives rise to dream-enactment behavior as an early clinical manifestation of brainstem neuropathology. In patients with isolated RBD, evidence of early neurodegeneration has been demonstrated by multiple techniques, including:

●Striatal dopamine transporter (DAT) imaging using 123I-FP-CIT single-photon emission computed tomography (DaTscan) [24-26]

●Metaiodobenzylguanidine (MIBG, iobenguane I-123) scintigraphy [27]

●Alpha-synuclein seed amplification assays in a range of tissues [28-32]

●Analysis of postmortem autopsy specimens [33,34]

Early clinical manifestations of PD, DLB, and MSA can also be observed in a subset of patients with isolated RBD, and these features are associated with increased risk for being clinically diagnosed with the disorder (referred to as phenoconversion).

In some cases, dual pathology that influences phenoconversion may be present. In particular, amyloid beta and hyperphosphorylated tau pathology of Alzheimer disease (AD) is much more common in isolated RBD than previously recognized, and its presence appears to increase the risk of phenoconversion to DLB [23,35]. In one postmortem study of 20 patients with isolated RBD, all patients had alpha-synuclein pathology and 70 percent also had amyloid beta plaques and neurofibrillary tangles [23]. In a separate study of living patients with isolated RBD, elevated cerebrospinal fluid (CSF) phospho-tau/amyloid-beta 42 predicted short-term conversion to DLB [36]. Further research is needed to validate whether Alzheimer copathology in isolated RBD determines whether a patient develops DLB or PD.

Rates of phenoconversion and counseling are reviewed below. (See 'Prognosis and counseling' below.)

Other neurologic disorders — Less commonly, RBD occurs in association with nonsynuclein neurodegenerative disorders, nondegenerative brainstem pathologies, and head injury.

●Nonsynuclein neurodegenerative disorders – RBD has been reported in patients with progressive supranuclear palsy, frontotemporal dementia, amyotrophic lateral sclerosis, AD, spinal cerebellar ataxia type 3, Huntington disease, and myotonic dystrophy type 2 [11,35,37-40].

Many of these disorders affect pontine regions that control REM sleep, supporting a causal role in RBD. With the exception of spinocerebellar ataxia type 3, these disorders are associated with a much lower prevalence of RBD compared with the alpha-synuclein disorders. In addition, symptoms of RBD in these cases typically arise after other neurologic deficits have manifested rather than before [41].

In some cases, however, there may be dual pathology, and alpha-synuclein pathology in the brainstem may be the more proximate cause of RBD. This has been demonstrated in patients with cognitive impairment that was presumed to be due to Alzheimer pathology in whom careful postmortem evaluations have demonstrated diffuse brain stem alpha-synuclein pathology [35].

●Brainstem pathologies – RBD can occur due to structural lesions in the pons or hypothalamus that disrupt neural circuits involved in REM sleep regulation, including stroke, tumors, and demyelination [42-45].

RBD has also been described in association with paraneoplastic and autoimmune encephalitides such as IgLON5 encephalopathy, anti-leucine rich glioma inactivated 1 (LGI1) encephalitis, anti-contactin associated protein-like 2 (Caspr2) encephalitis, as well as Wilson disease and cerebellar degeneration [46-49]. (See "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis".)

●Traumatic brain injury – RBD and other sleep-related movement disorders may occur with increased frequency after traumatic brain injury and in association with posttraumatic stress disorder (PTSD) [50]. (See "Sleep-wake disorders in patients with traumatic brain injury", section on 'Abnormal movements or behaviors during sleep'.)

Narcolepsy and orexin deficiency — Approximately 50 percent of patients with narcolepsy type 1 have RBD, and the pathogenesis (orexin deficiency) is distinct from other forms of RBD. (See 'Pathogenesis' above.)

The dream-enactment behavior of narcolepsy-related RBD is caused by a failure of orexin to stabilize REM sleep, with a resulting intrusion of wakeful muscle tone [19,21]. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Loss of orexin signaling'.)

Alpha-synuclein biomarkers are absent in patients with narcolepsy-related RBD, suggesting that they do not have an increased risk of neurodegeneration [51].

Medications — A variety of medications can cause or unmask RBD, the most common being the serotonin reuptake inhibitors (SSRIs) (table 1).

●Serotonergic antidepressants – RBD is a recognized adverse effect of serotonergic antidepressants including SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and serotonin modulating agents (table 1) [52,53]. Serotonergic RBD (5-HT RBD) appears to be the most prevalent form of RBD among the young (<40 years old) and, in contrast with isolated RBD, appears to occur as frequently in females as in males [10,52].

The magnitude of RBD risk associated with SSRIs and SNRIs is not well characterized, but they are known to increase REM sleep without atonia (RSWA; a polysomnography [PSG] marker of RBD) in patients without a history of dream enactment [54,55]. In a retrospective study of over 10,000 PSG examinations, RSWA was identified in 12 percent of participants who were taking an SSRI or SNRI versus 2 percent of the entire study population, representing a 10-fold increase in relative risk [55,56]. Only seven of the patients with antidepressant-associated RSWA carried a clinical diagnosis of RBD (0.5 percent).

Serotonergic raphe nuclei in the pons have an activating effect on the REM-off nuclei, suggesting a plausible pathological mechanism by which exogenous serotonergic agents could induce RSWA and trigger dream enactment [11]. Such effects may be most likely to lead to clinical symptoms in patients with comorbid brainstem dysfunction due to early alpha-synuclein deposition. In other words, serotonergic antidepressants may unmask RBD in individuals already at risk for underlying neurodegeneration.

This phenomenon is supported by observations that some patients with 5-HT RBD have other prodromal markers of alpha-synuclein neurodegeneration, such as hyposmia, constipation, abnormalities in color vision, and subtle motor impairments [57]. This point is emphasized by a study of RBD participants in the North American Prodromal Synucleinopathy (NAPS) consortium, which found similar motor and cognitive scores among those individuals with 5-HT RBD compared with those with isolated RBD not due to an SSRI [58].

●Other medications – Other less commonly reported medications that induce RBD include classes of agents also known to affect REM sleep. Emergent RBD has been reported in a patient with PD treated with suvorexant, a dual orexin receptor antagonist used for treatment of insomnia [59]. Other rare causes include beta blockers and cholinesterase inhibitors [5,60,61]. Withdrawal from alcohol, benzodiazepines, monoamine oxidase inhibitors, and barbiturates can precipitate RBD episodes as well (table 1).

CLINICAL FEATURES — 

Patients with rapid eye movement (REM) sleep behavior disorder (RBD) exhibit abnormal dream mentation and a wide spectrum of motor behaviors during REM sleep.

Clinical presentation — Symptoms of isolated RBD typically begin in late adulthood. The median age of diagnosis is 60 to 70 years [62-65]. In most cases, symptom onset is gradual and progressive, with a delay of several years between the onset of symptoms and diagnosis. Patients typically present to medical attention with a concern related to injurious or potentially injurious actions to themselves and/or a bed partner during sleep.

Dream-enactment behaviors — The defining symptom of RBD is repeated episodes of sleep-related vocalization and/or complex motor behaviors during REM sleep, correlating with dream mentation.

●Types of movements – The movements of RBD range from minor movements (eg, jerk of a hand or foot, finger twitches, facial grimace) to more complex and purposeful movements such as throwing a ball or flailing to protect oneself.

Simple, mild movements and vocalizations of mild intensity are the most common, but complex movements occur, at least intermittently, in most patients [66]. Sleep-related vocalizations may be loud and laden with expletives. Sleep-related injuries can arise from jumping out of bed or striking a bed partner. Events that involve leaving the bed pose the highest risk for self-injury.

In a cohort study of 203 consecutive patients with RBD followed at a tertiary care sleep clinic over a median of five years, only 66 percent of patients were aware of their sleep behaviors [67]. The majority of patients had experienced at least one episode of punching (87 percent), kicking (82 percent), falling out of bed (77 percent; in most cases, less than five times), gesturing (73 percent), or knocking over the nightstand (67 percent). Nearly all patients also reported vocalizations, most commonly talking (96 percent), screaming (90 percent), and moaning (64 percent). In both males and females, approximately 60 percent of patients and 20 percent of bed partners had sustained injury.

●Timing and frequency of episodes – Symptoms predominantly occur in the second half of the sleep period, when REM sleep is most prevalent. The frequency of events ranges from nightly to annually [5,68]. Among patients with narcolepsy and RBD, dream enactment tends to occur earlier in the sleep period and is composed of more simple movements that are less violent.

●Symptoms upon awakening – Patients often sleep through mild events. With more vigorous dream enactment, they typically wake up for a brief period of time and then fall back asleep. Patients may appear briefly confused when they first awaken but quickly orient to their surroundings. This is in contrast to sleepwalking, confusional arousals, and sleep terrors. (See 'Differential diagnosis' below.)

Dream content is often recalled at the time of awakening and is typically unpleasant (eg, dreaming of being attacked or chased, arguing with someone, or falling off a cliff) [67,69]. Dream content in patients with RBD is not more violent than in unaffected individuals, despite the violent behaviors. Importantly, patients are no more likely than controls to exhibit daytime violence or personality disturbances [70,71].

Neurologic findings — Patients with isolated RBD often have subtle, progressive motor and cognitive features consistent with early neurodegeneration. Typical findings include mild gait abnormalities, such as a unilateral decreased arm swing, consistent with subtle parkinsonism. Quantitative motor testing reveals dysarthria and limb bradykinesia imperceptible on a clinical examination [72,73].

Cognitive impairments are similar to those seen in patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB), with progressive deficits in visuoconstructional skills, facial expression recognition, color identification, and executive function [11,73-77]. Many patients will describe pareidolia (the tendency to interpret a vague visual feature as familiar, such as a face in the sand), a finding that correlates with underlying occipital dysfunction consistent with impending Lewy body disease [78].

Comorbid olfactory dysfunction, constipation, and orthostatic hypotension are frequently noted in cases of isolated RBD [73,79-82]. Like the motor and cognitive deficits, these impairments are similar to those seen in patients with PD [83]. (See "Clinical manifestations of Parkinson disease".)

Among patients with PD, those with RBD suffer a greater clinical burden with more rapid cognitive impairment, more psychiatric comorbidities, poorer treatment response, and more widespread brain atrophy compared with PD patients without RBD [84-88]. RBD appears to specifically predict more freezing of gait, and many of the same brainstem regions implicated in the pathophysiology of RBD mediate the pathogenesis of freezing of gait [89].

DIAGNOSIS — 

A diagnosis of rapid eye movement (REM) sleep behavior disorder (RBD) should be suspected in patients with a clinical history of recurrent dream-enactment behavior and confirmed by identifying REM sleep without atonia (RSWA) on video polysomnography (PSG) [5,90].

Evaluation — The clinical evaluation should include a detailed review of the sleep-wake complaints, a neuropsychiatric history, and complete physical and neurologic examination. A report from a bed partner is particularly helpful, as many patients are unable to properly recall the sleep-related events.

●History – RBD can often be detected with one question asked of the bed partner: "Have you ever seen the patient appear to 'act out their dreams' (punched or flailed arms in the air, shouted, or screamed) while sleeping?" [41]. Importantly, such screening questions are fairly sensitive for RBD, but they are not specific, as other sleep-disrupting conditions (such as obstructive sleep apnea, periodic limb movements [PLMs], confusional arousals, and nocturnal epilepsy) can cause similar movements [91].

The history should also pay specific attention to the timing of abnormal vocalizations or behaviors during the night. This feature helps distinguish RBD from other parasomnias such as confusional arousals, sleepwalking, and sleep terrors, as RBD is more likely to occur in the second half of the sleep period (figure 2). (See 'Differential diagnosis' below.)

Patients should be asked about potentially offending medications (eg, antidepressants (table 1)) as well as ancillary symptoms of alpha-synuclein neurodegenerative disorders, such as difficulty with smell, syncope, bowel motility, visual hallucinations, and tremor. When chronic, unexplained hyposmia, orthostasis, and constipation coexist with RBD, they are highly suggestive of an imminent alpha-synuclein disorder such as Parkinson disease (PD) or dementia with Lewy bodies (DLB) [11]. In young patients, symptoms of RBD in the absence of a serotonergic medication should prompt consideration of comorbid narcolepsy.

●Neurologic examination – A complete neurologic examination should be performed including a brief test of cognitive function (eg, Mini-Mental State Examination [MMSE] or Montreal Cognitive Assessment [MoCA]) and a motor examination to look for subtle or overt parkinsonism (ie, bradykinesia, rigidity, tremor). (See 'Neurologic findings' above and "Mental status scales to evaluate cognition".)

●Additional testing – Additional testing such as neuroimaging, electroencephalography, and neuropsychological batteries are warranted only if there is further evidence suggesting an undiagnosed neurodegenerative disorder [92]. Tests that identify central nervous system dopamine dysfunction (such as dopamine transporter [DAT] imaging) or other markers of synuclein pathology (such as metaiodobenzylguanidine [MIBG, iobenguane I-123] cardiac scintigraphy) are not necessary for the diagnosis of RBD but can be clinically useful in predicting and monitoring the course of the disease [11,93,94]. (See "Diagnosis and differential diagnosis of Parkinson disease" and "Clinical features and diagnosis of dementia with Lewy bodies" and "Multiple system atrophy: Clinical features and diagnosis".)

Video polysomnography — Video polysomnography (PSG) is necessary for definitive diagnosis of RBD and to exclude other sleep disorders that can mimic RBD (eg, obstructive sleep apnea, nocturnal seizures, PLMs) [5,95]. Home sleep apnea testing is not a useful test for RBD.

The characteristic PSG finding of RBD is RSWA, which is an elevation of motor tone during REM sleep as measured by electromyography (EMG) in the chin and/or limb leads (figure 3) [95-97]. Formal PSG criteria for RSWA developed by the American Academy of Sleep Medicine and others are reviewed separately. (See "Polysomnography in the evaluation of parasomnias and epilepsy", section on 'REM sleep behavior disorder'.)

When present, RSWA tends to occur during every REM cycle but is most prominent in the final REM period of the night. While there is little correlation between the severity of PSG findings and clinical symptoms, significant progression of RSWA over time may correlate with progression to RBD in subjects with isolated RSWA [98,99]. Dramatic behaviors are rarely captured during PSG; by contrast, more subtle, seemingly purposeful hand movements suggestive of dream enactment, referred to as REM sleep behavior events (RBEs), are often observed.

RSWA is occasionally detected in individuals without a reported history of dream-enactment behaviors, particularly in patients taking serotonergic antidepressants [56,100,101] and in older adults [102]. The reported prevalence of isolated RSWA in adults without a history of RBD ranges from 10 to 15 percent and varies according to how RSWA is defined [4,56,102-105]. The proportion of patients with isolated RSWA who later develop RBD has not been established; in one small study, 1 of 14 individuals with RSWA progressed to RBD over a mean of 8.6 years [98]. (See "Polysomnography in the evaluation of parasomnias and epilepsy", section on 'REM sleep behavior disorder'.)

In patients with comorbid narcolepsy, PSG may also demonstrate frequent shifts between REM and non-REM (NREM) sleep and consistent sleep state boundary dysfunction [19]. (See "Clinical features and diagnosis of narcolepsy in adults".)

Automated detection of dream-enactment movements and behaviors by traditional video recordings is under investigation and shows promise for improving accessibility of diagnosis [106]. Further validation studies are needed, however.

Diagnostic criteria — According the International Classification of Sleep Disorders, third edition, text revision (ICSD-3-TR), a diagnosis of RBD requires all of the following [5]:

●Repeated episodes of sleep-related vocalization and/or complex motor behaviors

●Behaviors are documented by PSG to occur during REM sleep or, based on clinical history of dream enactment, are presumed to occur during REM sleep

●Presence of RSWA on PSG (see 'Video polysomnography' above)

●The sleep disturbance is not better explained by another current sleep or mental disorder

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of rapid eye movement (REM) sleep behavior disorder (RBD) includes disorders of arousal, other REM-associated parasomnias such as nightmares, sleep-disrupting conditions such as periodic limb movement disorder (PLMD) and obstructive sleep apnea, nocturnal seizures, and dissociative psychiatric disorders. Although these disorders may sometimes be distinguished from each other by history, overnight polysomnography (PSG) is required for definitive diagnosis.

●Non-REM parasomnias – The most common disorders to be distinguished from RBD are the non-REM (NREM) parasomnias: confusional arousals, sleepwalking, and sleep terrors. Unlike RBD, NREM parasomnias usually present in childhood. Aspects of the history that are helpful in distinguishing NREM parasomnias from RBD include:

•Duration and timing of the events – RBD consists of brief dream enactment (<60 seconds) occurring in the latter half of the sleep period followed by alertness and orientation upon awakening. This presentation contrasts with sleepwalking, in which there is often a lifelong history of prolonged, amnestic, complex, nonviolent activities emanating from the first half of the sleep period. Similarly, confusional arousals are more prolonged (>60 seconds) and more often occur in the first half of the night (figure 2). (See "Disorders of arousal from non-rapid eye movement sleep in adults", section on 'Confusional arousals'.)

•Response upon awakening – Sleepwalking subjects are difficult to awaken and only rarely report clear dream mentation. By contrast, patients with RBD often recall dream content if awakened and are alert and oriented afterwards.

•Nature of vocalizations – In RBD, sleep-related vocalizations may be loud and laden with expletives. This contrasts with normal sleep talking, which is more typical of daytime conversation and occurs during both NREM and REM sleep [93]. Sleep terrors may be accompanied by a loud vocalization but have other features distinct from RBD. They are mostly limited to preadolescence and characterized by amnestic episodes of intense fear initiated by a sudden scream. They may last several minutes, during which time the patient is inconsolable. Patients are amnestic and unconcerned regarding the events, while parents or other caregivers often find them frightening [93]. (See "Parasomnias of childhood, including sleepwalking", section on 'Clinical features'.)

●Parasomnia overlap disorder – Parasomnia overlap disorder is characterized by RBD and either a disorder of arousal, sleep-related eating disorder, sexsomnia, or rhythmic movement disorder [5]. Compared with RBD, parasomnia overlap disorder has an earlier age of onset (often in childhood or adolescence) and may be comorbid with a variety of neurologic and psychiatric disorders such as narcolepsy and multiple sclerosis. (See "Disorders of arousal from non-rapid eye movement sleep in adults", section on 'Parasomnia overlap disorder'.)

●Nightmares – Nightmares are REM-related phenomena consisting of disturbing mentation and recalled in vivid detail. Unlike RBD, nightmares are not associated with motor activity or sleep-related injury [93]. In fact, nightmares are often characterized by sleep paralysis: an inability to move, defend oneself, or scream. (See "Nightmares and nightmare disorder in adults".)

●Obstructive sleep apnea – Behaviors that may mimic RBD can occur when REM sleep is fragmented by obstructive sleep apnea. However, these parasomnia-like behaviors resolve once the sleep-disordered breathing is effectively treated [11,92]. This phenomenon has been referred to as pseudo-RBD.

●Periodic limb movements – Periodic limb movements (PLMs) are lower extremity "triple flexion responses" (dorsiflexion of the ankle, flexion of the knee and hip) along with dorsiflexion of the toe, akin to the Babinski response. Unlike RBD, PLMs occur primarily during NREM sleep, are periodic (approximately every 45 seconds), and are unrelated to dream mentation [5,96]. Rare cases of frequent and vigorous PLMs during both NREM and REM sleep, mimicking RBD, have been described [107]. These pseudo-RBD patients often respond to therapies, such as dopaminergic agents, which are used in the treatment of PLMs. (See 'Management' below and "Polysomnography in the evaluation of abnormal movements during sleep", section on 'Periodic limb movements of sleep'.)

●Sleep-related hypermotor epilepsy – RBD is occasionally confused with sleep-related hypermotor epilepsy (previously called nocturnal frontal lobe epilepsy). This syndrome, which can be familial or sporadic, is characterized by stereotyped, recurrent (up to 20 episodes a night), abnormal behaviors. Electroencephalography may (but not universally) reveal epileptic activity. Compared with RBD, patients with sleep-related hypermotor epilepsy are younger (typically presenting in adolescence) and fully unaware of nighttime behaviors [92]. (See "Sleep-related epilepsy syndromes", section on 'Sleep-related focal epilepsies'.)

MANAGEMENT — 

Establishing a safe sleeping environment is the primary goal of treatment. This can be achieved through modification of the sleep environment and, if necessary, pharmacotherapy to suppress the abnormal movements during sleep (algorithm 1) [108-110].

General measures in all patients

Safe sleeping environment — The frequency of dream-enactment behaviors is not predictive of injury, so all patients with rapid eye movement (REM) sleep behavior disorder (RBD) and their bed partners should be counseled on modifying the sleeping environment to prevent injury. For patients with mild symptoms, this may be all that is needed.

The punching, kicking, and jumping behaviors can result in hematomas, fractures, lacerations, and joint dislocations [111]. Bed partners are frequently the target of violent dream enactment, and RBD has rarely been implicated in charges of domestic assault [112,113].

Firearms should not be accessible, and sharp or easily breakable furniture and objects (such as lamps) should be removed from the immediate sleeping area. In the event of continued vigorous behaviors, sleeping alone is advised. Some patients resort to using padded bed rails or sleeping in a sleeping bag [93].

Exiting the bed while acting out a dream is a high-risk behavior that may result in traumatic injury [112]. A bed alarm that delivers a customized calming message from a familiar voice at the onset of dream enactment can prevent a patient from exiting the bed and avert sleep-related injury [114].

Reversible factors — Medications known to exacerbate RBD, including the serotoninergic antidepressants, should be discontinued or avoided if possible in patients with RBD (table 1) [115]. Many cases of medication-associated dream enactment are self-limited following discontinuation of the offending medication.

In patients with a sleep-fragmenting condition such as obstructive sleep apnea, dream-enactment behavior often resolves when the underlying disorder is treated [11,93]. The duration and circadian timing of sleep should be optimized as well.

Patients with frequent/injurious behaviors — All patients with frequent, disruptive, or injurious behaviors should be treated with pharmacotherapy to reduce behaviors and lower risk of injury.

Melatonin (preferred in most patients) — Melatonin is our preferred first-line therapy in most patients with frequent, disruptive, or injurious behaviors (algorithm 1 and table 2). It tends to be better tolerated than the historical first-line therapy, clonazepam, especially in older adults with neurodegenerative disorders [116,117]. Cholinesterase inhibitors are a reasonable alternative in patients with mild cognitive impairment or dementia with Lewy bodies (DLB). However, if a patient is having concerning, ongoing, potentially injurious dream enactment on a cholinesterase inhibitor, we recommend expeditiously adding melatonin. (See 'Cholinesterase inhibitors (comorbid cognitive impairment)' below.)

●Administration – The dose of melatonin required to suppress behaviors in patients with RBD varies. In our experience, most patients achieve significant improvement with doses ranging from 6 to 18 mg nightly. We typically start with 3 mg at night and then increase in 3 mg increments until the disruptive and injurious behaviors have ceased (table 2). Use of extended-release melatonin has a theoretical but unproven advantage over immediate-release formulations. For extended-release melatonin, a suggested starting dose is 5 mg, titrating by 5 mg every one to two weeks to a maximum of 15 mg nightly.

Melatonin tends to be well tolerated at these doses, with occasional patients developing gastrointestinal distress or headache that is dose limiting. Other reported side effects are usually mild and include sleepiness, fatigue, dizziness, unsteadiness, and cognitive alteration [116].

Melatonin is not regulated by the US Food and Drug Administration and is available in a variety of formulations over-the-counter. Unlicensed, nonprescription products can vary widely due to differences in the type of preparation and additives used. In our experience, most formulations appear to be clinically equivalent. Melatonin undergoes hepatic metabolism and should be used with caution in patients with liver dysfunction.

Behaviors typically return when melatonin is reduced or discontinued, and most patients require lifelong therapy. If behaviors are inadequately suppressed with melatonin, low-dose clonazepam or a cholinergic agent is an effective add-on or alternative therapy. (See 'Clonazepam (alternative or add-on)' below and 'Cholinesterase inhibitors (comorbid cognitive impairment)' below.)

●Mechanism of action – Melatonin is an endogenous hormone normally secreted by the pineal gland in response to evening darkness, entraining circadian rhythms. Studies in patients with RBD confirm alterations in circadian rhythms [118,119]. Melatonin in high doses at bedtime (6 to 18 mg) augments REM sleep atonia and improves RBD symptoms [116,120,121]. In addition to suppressing REM motor tone, melatonin normalizes other circadian features of sleep, and these improvements persist for several days after melatonin is discontinued [119].

●Efficacy – In several observational studies and one small, randomized trial, the majority of patients treated with melatonin experienced at least partial improvement in the frequency and severity of RBD symptoms and a reduced likelihood of injury [116,120-124]. In a retrospective study that included 45 patients with RBD, melatonin and clonazepam were similarly effective, and melatonin was better tolerated [124]. Approximately two-thirds of patients treated with melatonin reported at least mild improvement in symptoms, and 12 percent had complete resolution of RBD behaviors. Patients on melatonin reported fewer falls and injuries post-treatment compared with clonazepam.

Clonazepam (alternative or add-on) — Low-dose clonazepam (starting at 0.25 to 0.5 mg orally at bedtime) is an alternative to melatonin for RBD or as add-on therapy in patients with an inadequate response to melatonin.

●Administration – The usual effective dose range for RBD is 0.5 to 1 mg nightly. The therapeutic mechanisms of clonazepam in RBD are not fully understood, although it is thought that clonazepam may reduce the frequency of unpleasant dreams, thus decreasing violent dream-enactment behavior [125].

Although low doses of clonazepam (0.5 to 1 mg at bedtime) are typically sufficient to suppress RBD behaviors, side effects can limit its utility. In a cohort study that included 167 patients treated with clonazepam (mean effective dose 1 mg), 39 percent of patients reported side effects, most commonly morning sedation and dizziness, leading to drug discontinuation in 9 percent [67].

Side effects of clonazepam can be particularly problematic among older adults and in the setting of advanced neurodegenerative disease, where its prolonged duration of action may result in morning sedation as well as gait and cognitive impairment [114,126]. In such patients, we suggest a lower initial dose (eg, 0.125 or 0.25 mg) and close monitoring for the emergence of toxicity (table 2). Patients who do require long-term therapy can be reassured by a study indicating that clonazepam does not appear to permanently impair cognition [127]. Clonazepam undergoes hepatic metabolism and should be used with caution in patients with liver dysfunction.

●Efficacy – Clonazepam has long been recognized as a treatment for RBD [117]. In four large case series, clonazepam was associated with complete resolution of RBD symptoms in 55 to 79 percent of patients and partial reduction in an additional 11 to 32 percent [62,63,67,128]. It was reassuring that clonazepam therapy had sustained efficacy without significant dose escalation over years of nightly use [128]. However, follow-up studies describe more mixed results, ranging from sustained benefit without dose escalation to a high incidence of increasing dose requirements and, ultimately, treatment failure [122,125,129-133]. In a head-to-head trial between clonazepam and prolonged-release melatonin, clonazepam demonstrated superior efficacy for RBD symptoms but with more significant side effects [134].

Cholinesterase inhibitors (comorbid cognitive impairment) — Cholinesterase inhibitors such as donepezil and rivastigmine, which are commonly used to treat cognitive impairment in patients with Alzheimer disease (AD) and DLB, appear to decrease dream enactment in patients with RBD, even in the absence of cognitive symptoms. These agents are a reasonable alternative to melatonin for patients with RBD and mild cognitive impairment or DLB who are not already taking a cholinesterase inhibitor, as they may help treat both conditions [117]. We tend to use rivastigmine because it has been studied in a randomized trial, but donepezil may have similar effects.

In one placebo-controlled crossover trial, rivastigmine reduced the number of dream-enactment behavior episodes (as noted by bed partners) in patients with Parkinson disease (PD) and RBD [135]. Rivastigmine is administered by transdermal patch, and dosing typically starts at 4.6 mg applied every 24 hours. The dose can be titrated up to a maximum of 13.3 mg daily. Donepezil, another cholinesterase inhibitor, has also been reported to improve RBD symptoms in three patients [136].

Other therapies — While dopaminergic medications (eg, levodopa, pramipexole, ropinirole) are the standard therapy for daytime motor symptoms of PD, they are rarely effective for RBD alone.

Pramipexole has been reported to effectively treat RBD when there are frequent periodic limb movements (PLMs) during non-REM (NREM) sleep. In these cases, it is possible that pramipexole is primarily treating sleep fragmentation caused by PLMs (ie, PLM disorder [PLMD]) [137-139]. Thus, we recommend avoiding pramipexole for the treatment of RBD unless frequently ancillary, dopaminergic responsive motor activity is present on polysomnography (PSG).

Other agents with some reported success include imipramine, carbamazepine, sodium oxybate, triazolam, zopiclone (available outside the United States), quetiapine, and clozapine [122,130,140-142].

Surgeries for PD often improve sleep consolidation and decrease daytime sleepiness but do not improve RBD symptoms or the PSG findings of RBD. In four case series of patients with PD, deep brain stimulation of the subthalamic nuclei was associated with improvement in subjective sleep quality and sleep architecture on PSG; however, there was little to no improvement in dream-enactment behavior or REM atonia [143-146].

PROGNOSIS AND COUNSELING

Risk of neurodegenerative disease — Most older adults with isolated RBD eventually develop an alpha-synuclein neurodegenerative disorder with a phenotype of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) [111,147-149]. The interval between the onset of dream enactment and diagnosis of PD or a related disorder can vary from months to decades [150,151].

Older age at onset of dream enactment is the most important risk factor for phenoconversion, and adults diagnosed with RBD at 70 years of age or older are at highest risk [152]. This was demonstrated in a retrospective study that included 372 patients with isolated RBD (50 percent males; median age at RBD diagnosis 62.5 years for males and 54.9 years for females) in which risk of phenoconversion rose steadily by age at diagnosis:

●Age <50 years – 5-, 10-, and 14-year conversion rates of 0, 1.6, and 1.6 percent, respectively

●Age 50 to 60 years – 5-, 10-, and 14-year conversion rates of 2.5, 9, and 9 percent, respectively

●Age 61 to 70 years – 5-, 10-, and 14-year conversion rates of 6, 22, and 36 percent, respectively

●Age >70 years – 5-, 10-, and 14-year conversion rates of 15, 67, and 84 percent, respectively

Additional clinical risk factors for conversion to an alpha-synucleinopathy in patients with isolated RBD are well studied [151], although an individualized risk assessment remains difficult [22]. In a multicenter prospective cohort study of 1280 patients with isolated RBD and a mean follow-up of 4.6 years, the strongest risk factors for conversion to a neurodegenerative disorder were abnormal quantitative motor testing (hazard ratio [HR] 3.2), objective motor examination findings (HR 3.0), olfactory dysfunction (HR 2.6), erectile dysfunction in males (HR 2.1), abnormal color vision (HR 1.7), and constipation (HR 1.7) [150]. Factors associated with lower risk of conversion include younger age, female sex, and use of antidepressants [150,152]. Emerging data also suggest that cerebrospinal fluid (CSF) alpha-synuclein seed amplification assays are predictive of phenoconversion to either PD or DLB [36], similar to skin biopsy data. (See 'Skin biopsy in prodromal phase' below.)

Two proposed staging systems for neuronal alpha-synuclein disorders (PD and DLB) are intended to provide biomarker-established stages for clinical trials of neuroprotective strategies and may eventually be validated and used clinically [153,154]. These staging systems integrate a clinical prodrome, such as RBD, with a tissue diagnosis of synuclein pathology and a measure of dopaminergic dysfunction. Depending upon the staging system, the tissue diagnosis can be made by seed amplification assays or immunohistochemical detection of alpha-synuclein pathology on CSF or skin biopsy. Dopamine neuronal dysfunction can be identified by imaging such as dopamine transporter (DAT) imaging. (See "Diagnosis and differential diagnosis of Parkinson disease", section on 'Biological definition and staging system'.)

Skin biopsy in prodromal phase — Skin biopsy can provide direct histopathologic confirmation of underlying alpha-synuclein neurodegeneration in patients with isolated RBD [30,51]. A commercially available diagnostic tool for identifying synuclein pathology in cutaneous nerves has been developed [32], which may be an ideal test to screen for evidence of prodromal disease among patients interested in this information for the purposes of prognosis and clinical trial participation. (See 'Prognostic disclosure' below.)

The presence of cutaneous phosphorylated alpha-synuclein is close to 100 percent specific for a systemic synucleinopathy [29-32,51]. In cross-sectional studies, positivity rates in people with isolated RBD range from approximately 60 to 90 percent, which contrasts with 0 percent in healthy controls and people with narcolepsy-related RBD or Alzheimer disease (AD) [22]. Importantly, in isolated RBD, cutaneous deposits are frequently identified in the absence of other biomarkers (such as Lewy body-type cognitive dysfunction or clinical parkinsonian motor deficits), suggesting the utility of skin biopsy to identify individuals with early systemic pathology of either DLB or PD [29-32,51].

Prognostic disclosure — A discussion about the neurodegenerative risks associated with a diagnosis of isolated RBD is usually appropriate but must be balanced by uncertainties, especially with regard to patient-specific risk, and by patient preferences with regard to disclosure [155-157]. Clinicians should bear in mind that a diagnosis of RBD is not a guarantee of future neurodegenerative disease but rather suggests an increased susceptibility. Risk estimates are derived from selected populations and do not equate to definitive information on a patient's individual risk.

Clinicians may reasonably worry about causing excess anxiety by disclosing a possible neurodegenerative condition to patients with RBD. Conversely, withholding risk information may harm the provider-patient relationship, as patients and caregivers are likely to discover the association through an internet search. Some experts suggest only disclosing information to patients who desire the information. For example, the clinician can first ask, "Would you be willing to know more about the links between RBD and neurologic conditions?" [158].

In patients with isolated RBD, several studies have found that a large majority (>90 percent) indicate a preference for risk disclosure, citing future planning and the opportunity to be involved in research [158,159]. The generalizability of these studies may be limited, however, since surveyed patients were already involved in research on RBD. Studies in more diverse samples of patients are needed.

Communication should be tailored to the individual patient and take into account age, comorbidities, examination findings, caregiver support, medical literacy, and sociocultural background. Disclosure can take place gradually, over several visits. During this time, patients should be monitored for early signs of neurodegeneration that may further inform risk. When risk is discussed, it is important to provide balanced information that includes actionable steps that may be taken for those who wish to make lifestyle changes.

Discussing the association openly with patients, families, and caregivers has several potential benefits.

●Disclosure provides patients with the opportunity to ask questions and avoids the potential for misinformation.

●Patients can use the information to adopt healthier lifestyle habits that may decrease their risk of PD or other neurodegenerative disorders. As an example, growing evidence suggests that intermittent intense aerobic exercise may decrease PD risk [160]. We encourage our patients with RBD to maintain an active lifestyle with at least 30 minutes of intense aerobic exercise (heart rate >80 percent of maximum) three to four times per week.

●Patients with isolated RBD may be candidates for trials of neuroprotective therapies to impede or halt PD. A consortium of multinational investigators, the International Rapid Eye Movement Sleep Behavior Disorder Study Group, meets annually to promote the development of collaborative clinical trials [161]. For interested patients, the North American Prodromal Synucleinopathy (NAPS) Consortium is actively recruiting patients with RBD for trials of potential disease-modifying therapies.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Parasomnias, hypersomnias, and circadian rhythm disorders".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Rapid eye movement (REM) sleep behavior disorder (The Basics)")

Patients and caregivers can also be referred to the North American Prodromal Synucleinopathy (NAPS) Consortium website for educational material and information on research opportunities.

SUMMARY AND RECOMMENDATIONS

●Definition – Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment that emerges after a loss of REM sleep atonia. Behaviors are brief, correlate with dream mentation, mainly occur in the second half of the night, and, when violent, can result in injury to the patient or bed partner. (See 'Dream-enactment behaviors' above.)

●Prevalence – The prevalence of RBD is estimated at 0.5 to 1.5 percent in the general adult population, with higher frequencies among older adults and those with Parkinson disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). (See 'Prevalence and risk factors' above.)

●Etiology – Most cases of RBD are caused by alpha-synuclein neurodegeneration. RBD is also caused by antidepressant medications (table 1), narcolepsy, and pontine lesions such as those from stroke or multiple sclerosis. (See 'Etiology' above.)

●Diagnosis – The diagnosis of RBD is based upon a history of dream-enactment behavior and REM sleep without atonia (RSWA), as documented by video polysomnography (PSG). (See 'Diagnosis' above.)

●Differential diagnosis – The differential diagnosis of RBD includes non-REM (NREM) parasomnias (confusional arousals, sleepwalking, sleep terrors); nightmares; benign sleep-talking; nocturnal frontal lobe epilepsy; as well as sleep-fragmenting conditions such as obstructive sleep apnea and periodic limb movements (PLMs). (See 'Differential diagnosis' above.)

●Management

•Establish safe sleeping environment – All patients with RBD and their bed partners should be counseled on ways to alter the sleeping environment to prevent injury. (See 'Safe sleeping environment' above.)

•Reversible factors – Medications known to exacerbate RBD, including the serotoninergic antidepressants (table 1), should be discontinued, minimized, or avoided if possible. Sleep disorders such as obstructive sleep apnea should be diagnosed and treated. (See 'Reversible factors' above.)

•Pharmacotherapy – For patients with frequent, disruptive, or injurious behaviors, we recommend pharmacotherapy (Grade 1B). For most patients, we suggest melatonin as initial therapy rather than clonazepam or a cholinesterase inhibitor (algorithm 1) (Grade 2C). This preference is based largely on tolerability and the desire to minimize benzodiazepines in older adults and those with cognitive dysfunction. Dosing is provided in the table (table 2). (See 'Melatonin (preferred in most patients)' above and 'Clonazepam (alternative or add-on)' above.)

A cholinesterase inhibitor (eg, rivastigmine patch) is a reasonable alternative to melatonin in patients with mild cognitive impairment or DLB who are not already taking one, as it may help treat both conditions. (See 'Cholinesterase inhibitors (comorbid cognitive impairment)' above.)

●Prognosis and counseling – Most patients with isolated RBD eventually develop either PD or another disorder of alpha-synuclein neurodegeneration. The phenoconversion rate is approximately 50 percent every decade. The presence of hyposmia, constipation, and orthostasis increases the likelihood of earlier conversion. (See 'Prognosis and counseling' above.)

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Topic 14894 Version 56.0

References

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73 : Evolution of prodromal Parkinson's disease and dementia with Lewy bodies: a prospective study.

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76 : [Neurological disease and facial recognition].

77 : How does dementia with Lewy bodies start? prodromal cognitive changes in REM sleep behavior disorder.

78 : Pareidolias in REM Sleep Behavior Disorder: A Possible Predictive Marker of Lewy Body Diseases?

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81 : Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD.

82 : Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder.

83 : Comparison study of olfactory function and substantia nigra hyperechogenicity in idiopathic REM sleep behavior disorder, Parkinson's disease and normal control.

84 : Manifestations of Parkinson disease differ in association with REM sleep behavior disorder.

85 : Rapid eye movement sleep behavior disorder and subtypes of Parkinson's disease.

86 : REM sleep behavior disorder and neuropathology in Parkinson's disease.

87 : Quantitative assessment of motor speech abnormalities in idiopathic rapid eye movement sleep behaviour disorder.

88 : Brain atrophy in Parkinson's disease with polysomnography-confirmed REM sleep behavior disorder.

89 : Increased REM sleep without atonia in Parkinson disease with freezing of gait.

90 : Increased REM sleep without atonia in Parkinson disease with freezing of gait.

91 : Low Specificity of Rapid Eye Movement Sleep Behavior Disorder Questionnaires: Need for Better Screening Methods.

92 : Low Specificity of Rapid Eye Movement Sleep Behavior Disorder Questionnaires: Need for Better Screening Methods.

93 : Parasomnias: an updated review.

94 : Predictive markers for early conversion of iRBD to neurodegenerative synucleinopathy diseases.

95 : Diagnostic tools for REM sleep behavior disorder.

96 : Diagnostic tools for REM sleep behavior disorder.

97 : Video-polysomnography procedures for diagnosis of rapid eye movement sleep behavior disorder (RBD) and the identification of its prodromal stages: guidelines from the International RBD Study Group.

98 : Long-Term Follow-up Investigation of Isolated Rapid Eye Movement Sleep Without Atonia Without Rapid Eye Movement Sleep Behavior Disorder: A Pilot Study.

99 : Evolution of Prodromal REM Sleep Behavior Disorder to Neurodegeneration: A Retrospective Longitudinal Case-Control Study.

100 : Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder.

101 : Increased chin muscle tone during all sleep stages in children taking selective serotonin reuptake inhibitor antidepressants and in children with narcolepsy type 1.

102 : Normative and isolated rapid eye movement sleep without atonia in adults without REM sleep behavior disorder.

103 : Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications.

104 : Polysomnographic diagnosis of idiopathic REM sleep behavior disorder.

105 : A quantitative analysis of the submentalis muscle electromyographic amplitude during rapid eye movement sleep across the lifespan.

106 : Automated Detection of Isolated REM Sleep Behavior Disorder Using Computer Vision.

107 : Periodic Limb Movements During Sleep Mimicking REM Sleep Behavior Disorder: A New Form of Periodic Limb Movement Disorder.

108 : The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease.

109 : Management of REM sleep behavior disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

110 : Symptomatic treatment of REM sleep behavior disorder (RBD): A consensus from the international RBD study group - Treatment and trials working group.

111 : Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series.

112 : Potentially lethal behaviors associated with rapid eye movement sleep behavior disorder: review of the literature and forensic implications.

113 : Potentially lethal behaviors associated with rapid eye movement sleep behavior disorder: review of the literature and forensic implications.

114 : A novel therapy for REM sleep behavior disorder (RBD).

115 : Rapid eye movement sleep parasomnias.

116 : Melatonin therapy for REM sleep behavior disorder: a critical review of evidence.

117 : Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline.

118 : Alteration of circadian sleep-wake rhythm and salivary melatonin secretion in idiopathic/isolated REM sleep behavior disorder: Preliminary evidence.

119 : Loss of REM sleep features across nighttime in REM sleep behavior disorder.

120 : Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients.

121 : A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder.

122 : Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam.

123 : Melatonin therapy for REM sleep behavior disorder.

124 : Treatment outcomes in REM sleep behavior disorder.

125 : A prospective, naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder.

126 : Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound.

127 : Minimal effect of long-term clonazepam on cognitive function in patients with isolated rapid eye movement sleep behavior disorder.

128 : Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults.

129 : REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP.

130 : Update on the pharmacology of REM sleep behavior disorder.

131 : Rapid eye movement sleep behavior disorder.

132 : An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder.

133 : Clonazepam for probable REM sleep behavior disorder in Parkinson's disease: A randomized placebo-controlled trial.

134 : Comparative efficacy of prolonged-release melatonin versus clonazepam for isolated rapid eye movement sleep behavior disorder.

135 : Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson's disease.

136 : Treatment of REM sleep behavior disorder with donepezil: a report of three cases.

137 : Factors associated with the effect of pramipexole on symptoms of idiopathic REM sleep behavior disorder.

138 : Effectiveness of pramipexole, a dopamine agonist, on rapid eye movement sleep behavior disorder.

139 : Predictors of anxiety in early-stage Parkinson's disease - Results from the first two years of a prospective cohort study.

140 : Best practice guide for the treatment of REM sleep behavior disorder (RBD).

141 : A Case of Rapid Eye Movement Sleep Behavior Disorder in Parkinson Disease Treated With Sodium Oxybate.

142 : Sodium oxybate in treatment-resistant rapid-eye-movement sleep behavior disorder.

143 : Hallucinations, REM sleep, and Parkinson's disease: a medical hypothesis.

144 : Prevalence and clinical importance of sleep apnea in the first night after cerebral infarction.

145 : Effects of deep brain stimulation of the subthalamic nucleus on sleep architecture in parkinsonian patients.

146 : The Impact of Subthalamic Deep Brain Stimulation on Sleep-Wake Behavior: A Prospective Electrophysiological Study in 50 Parkinson Patients.

147 : Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients.

148 : Idiopathic REM sleep behaviour disorder and neurodegeneration - an update.

149 : Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials.

150 : Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study.

151 : Possible predictors of phenoconversion in isolated REM sleep behaviour disorder: a systematic review and meta-analysis.

152 : Phenoconversion in Women and Men With Isolated REM Sleep Behavior Disorder: A Retrospective Cohort Study.

153 : A biological definition of neuronalα-synuclein disease: towards an integrated staging system for research.

154 : A biological classification of Parkinson's disease: the SynNeurGe research diagnostic criteria.

155 : Ethical considerations in REM sleep behavior disorder.

156 : Idiopathic REM sleep behavior disorder and neurodegenerative risk: To tell or not to tell to the patient? How to minimize the risk?

157 : Specialist approaches to prognostic counseling in isolated REM sleep behavior disorder.

158 : The Views of Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder on Risk Disclosure.

159 : Patient values and preferences regarding prognostic counseling in isolated REM sleep behavior disorder.

160 : Neuroprotection in idiopathic REM sleep behavior disorder: a role for exercise?

161 : Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group.

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