SUMMAR Y Rapid eye movement (REM) sleep behaviour disorder (RBD) has been suggested to predict the development of neurodegenerative disorders. Patients with RBD are acting out dream behaviour associated with loss of normal muscle atonia of REM sleep. The aim of the present study was to confirm that exogenous melatonin improves RBD. Eight consecutively recruited males (mean age 54 years) with a polysomnographically (PSG) confirmed diagnosis of RBD were included in a two-part, randomized, doubleblind, placebo-controlled cross-over study. Patients received placebo and 3 mg of melatonin daily in a cross-over design, administered between 22:00 h and 23:00 h over a period of 4 weeks. PSG recordings were performed in all patients at baseline, at the end of Part I of the trial and at the end of Part II of the trial. Compared to baseline, melatonin significantly reduced the number of 30-s REM sleep epochs without muscle atonia (39% versus 27%; P = 0.012), and led to a significant improvement in clinical global impression (CGI: 6.1 versus 4.6; P = 0.024). Interestingly, the number of REM sleep epochs without muscle atonia remained lower in patients who took placebo during Part II after having received melatonin in Part I (-16% compared to baseline; P = 0.043). In contrast, patients who took placebo during Part I showed improvements in REM sleep muscle atonia only during Part II (i.e. during melatonin treatment). The data suggest that melatonin might be a second useful agent besides clonazepam in the treatment of RBD.k e y w o r d s chronobiotic, circadian rhythms, lewy body dementia, melatonin, neurodegenerative disorder, rem sleep behaviour disorder, rbd, sleep disorders

The study suggests that dronabinol was able to reduce nocturnal motor activity and agitation in severely demented patients. Thus, it appears that dronabinol may be a safe new treatment option for behavioral and circadian disturbances in dementia.

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Recent data suggest that melatonin may influence human physiology, including the sleep-wake cycle, in a time-dependent manner via the body's internal clock. Rapid-eye-movement (REM) sleep expression is strongly circadian modulated, and the impact of REM sleep on primary brain functions, metabolic processes, and immune system function has become increasingly clear over the past decade. In our study, we evaluated the effects of exogenous melatonin on disturbed REM sleep in humans. Fourteen consecutive outpatients (five women, nine men; mean age, 50 yr) with unselected neuropsychiatric sleep disorders and reduced REM sleep duration (25% or more below age norm according to diagnostic polysomnography) were included in two consecutive, randomized, double-blind, placebo-controlled, parallel design clinical trials. Patients received 3 mg melatonin daily, administered between 2200 and 2300 h for 4 wk. The results of the study show that melatonin was significantly more effective than placebo: patients on melatonin experienced significant increases in

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