Effectiveness of Pramipexole, a Dopamine Agonist, on Rapid Eye Movement Sleep Behavior Disorder

Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is parasomnia characterized by REM sleep without atonia (RWA) and elaborate motor activity in association with dream mentation. Periodic leg movement during sleep (PLMS) is observed in a large share of patients with RBD, suggesting a common pathology: dopaminergic dysfunction. This study was undertaken to evaluate the effectiveness and mechanism of action of pramipexole, a dopamine agonist, on RBD symptoms. Fifteen patients (57-75 years old) with RBD with a PLMS index of more than 15 events/h shown by nocturnal polysomnography were enrolled. Sleep variables, the score of severity for RBD symptoms, REM density, and PLM index were compared before and after one month or more of consecutive pramipexole treatment. Correlation analysis was conducted between the rate of change in RBD symptoms and the rate of reduction of REM density. Fourteen patients with RBD (80.0%) achieved symptomatic improvement of RBD with pramipexole treatment, which reduced REM density and PLM index during non-REM sleep despite the unchanged amount of RWA. The rate of change in RBD symptoms correlated positively with the rate of REM density reduction. Significant reduction of the PLM index was observed in non-REM sleep but not in REM sleep. Periodic leg movement during sleep (PLMS) is often comorbid with RBD, suggesting a common pathogenesis of the two disorders. Its frequency in RBD is higher than that seen in the normal population, especially during the REM sleep period (Fantini et al. 2002). Although two previous case series investigated the effectiveness of pramipexole on RBD symptoms (Fantini et al. 2003;Schmidt et al. 2006), these studies did not respectively examine the effect of pramipexole on PLMS during non-REM (NREM) and REM sleep periods. Moreover, the pathophysiology of PLMS in idiopathic RBD remains unsolved.Episodes of violent behavior in RBD are mostly associated with nightmares. However, no report describes the effectiveness of pramipexole for alleviating nightmares in RBD or its relation to REM density, which possibly triggers dream imagery (Ogawa et al. 2005).To elucidate the mechanism of pramipexole action on the pathogenesis of RBD, we investigated its effects on RBD symptoms, with particular attention to REM-related parameters and PLMS in this pilot study. Methods Subjects

Effects of Rotigotine on REM Sleep Behavior Disorder in Parkinson Disease

“…Kumru et al 7 did not find any difference in sleep measures detected on video recordings. Sasai et al 22 reported reduced REM density, and the rate of change in RBD symptoms was positively correlated with the rate of REM density reduction. Our study reports for the first time that rotigotine increases TST and the stage 1 % of patients, which was consistent with the result that the PDSS-2 scores decreased after rotigotine treatment.…”

“…In these studies, no differences were observed in sleep architecture or general sleep measure variables after treatment. 7,21,22 However, Fantini et al reported that pramipexole increased tonic, but not phasic, electromyographic activity during REM sleep, 21 and a reduction in the sleep motor behaviors was confirmed by video recording. Kumru et al 7 did not find any difference in sleep measures detected on video recordings.…”

“…20 Dopamine agonists, such as pramipexole, 6 have been reported as sufficient effective drugs for treatment of RBD. Three small case studies reported that approximately 61.7% ~ 89% of idiopathic RBD (iRBD) patients experienced a reduction in RBD symptoms after pramipexole treatment, 6,21,22 whereas Kumru 7 reported that pramipexole did not modify RBD related symptoms or VPSG abnormalities in PD patients (symptomatic RBD, sRBD). However, these conclusions were unconvincing due to the differing entrance criteria (iRBD patients, sRBD patients, or both of them); without a validated evaluation scale for the severity of RBD symptoms 6,7,21 ; without VPSG data in some studies.…”

Rapid Eye Movement Sleep Behavior Disorder: Overview and Current Perspective

“…A study of 14 patients demonstrated improvement in RBD in 80 % cases with reduction in REM density and PLM index but no change in RSWA [81].…”

Seeking Good Alternatives to Clonazepam: Suggestions for Future Treatment Trials in REM Sleep Behavior Disorder

“…As an objective measurement of treatment efficacy, reduction in REM sleep without atonia (RWA) measured by polysomnography (PSG) was reported in previous melatonin studies 4,5 ; however, the results of our present study of ramelteon and a previous study of pramipexole indicate their efficacy in treating RBD may be independent of reduced RWA. 6,7 The RBD severity scale (RBDSS) represents a further objective measure of the severity of RBD using video-PSG; however, measurements of RBDSS differed in 60% of patients between nights 1 and 2 in the original report. 8 In a previous retrospective melatonin study and clonazepam, the visual analog scale (VAS), a simple and clear subjective scale, was used to evaluate treatment efficacy, was used by a bed partner or family member to evaluate RBD frequency and severity in daily life.…”