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Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder.

ABSTRACT: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically occurs in the context of synuclein-based neurodegenerative disorders but can also be seen accompanying brain lesions and be exacerbated by medications, particularly antidepressants. There is also an increasing appreciation regarding isolated or idiopathic RBD (iRBD). Symptomatic treatment of RBD is a priority to prevent injurious complications, with usual choices being melatonin or clonazepam. The discovery that iRBD represents a prodromal stage of incurable synucleinopathies has galvanized the research community into delineating the pathophysiology of RBD and defining biomarkers of neurodegeneration that will facilitate future disease-modifying trials in iRBD. Despite many advances, there has been no progress in available symptomatic or neuroprotective therapies for RBD, with recent negative trials highlighting several challenges that need to be addressed to prepare for definitive therapeutic trials for patients with this disorder. These challenges relate to i) the diagnostic and screening strategies applied to RBD, ii) the limited evidence base for symptomatic therapies, (iii) the existence of possible subtypes of RBD, (iv) the relevance of triggering medications, (v) the absence of objective markers of severity, (vi) the optimal design of disease-modifying trials, and vii) the implications around disclosing the risk of future neurodegeneration in otherwise healthy individuals. Here, we review the current concepts in the therapeutics of RBD as it relates to the above challenges and identify pertinent research questions to be addressed by future work.

SUBMITTER: Matar E

PROVIDER: S-EPMC8116413 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Study objectivesREM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD.DesignWe comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables.SettingTertiary-care sleep center.ParticipantsParticipants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls.InterventionsN/A.Measurements and resultsRSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P < 0.01). RSWA distribution and type also differed between antidepressant-treated patients having higher values in anterior tibialis, and PD-RBD with higher submentalis and tonic RSWA. Psychiatric RBD had significantly younger age at onset than traditional RBD patients (P < 0.01).ConclusionsAntidepressant treatment was associated with elevated REM sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD.

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Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder.

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