Effects of long-term use of clonazepam on nonrapid eye movement sleep patterns in rapid eye movement sleep behavior disorder

Objective: We aim to analyze in detail the characteristics of nonrapid eye movement (NREM) sleep in drug-free patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). We compare drug-free iRBD patients to both normal controls and drug-free patients with narcolepsy/RBD and evaluate the changes following the long-term use of bedtime clonazepam. Participants and methods: Forty-six participants were recruited: 15 with iRBD (13 men, 2 women; mean age, 65.8 +/- 4.39 years), 13 with narcolepsy/RBD (10 men, 3 women; mean age, 63.0 +/- 6.73 years), and 18 normal controls (10 men, 8 women; mean age 69.4 +/- 7.72 years). Sleep was video polysomnographically recorded and the RBD severity scale (RBDSS) was obtained. Chin electromyography (EMG) amplitude was quantitatively assessed and the atonia index was computed. Additionally, NREM sleep instability was evaluated using an automatic quantitative analysis. Participants with iRBD were re-evaluated after 2.75 +/- 1.62 years of regular therapy with 0.5 to 1-mg clonazepam at bedtime. Results: Slow transient electroencephalography (EEG) events were increased in iRBD and decreased in narcolepsy/RBD, while fast transient events decreased in iRBD and increased in narcolepsy/RBD. During rapid eye movement (REM) sleep the atonia index was reduced in both iRBD and narcolepsy/RBD groups and during NREM sleep atonia index was increased in iRBD participants, remaining low in narcolepsy/RBD participants. After long-term therapy with clonazepam, wakefulness after sleep onset was decreased together with an increase in both slow-wave sleep (SWS) and sleep stage 2, in which the latter reached statistical significance; sleep stages 1 and 2 instability significantly decreased and the duration of EEG transients also slightly but significantly decreased. Finally, chin tone was not modified by clonazepam. Conclusions: Our study confirms that clonazepam modifies some aspects of NREM sleep in iRBD participants with a decrease in its instability. Moreover, we also show that a complex modification of sleep chin atonia exists in these participants, which also involves NREM sleep; for iRBD more complex neuropathologic models encompassing REM sleep and NREM sleep mechanisms are needed. (c) 2013 Elsevier B.V. All rights reserved.