Exogenous melatonin in periodic limb movement disorder: an open clinical trial and a hypothesis.

STUDY OBJECTIVES: The etiology of Periodic Limb Movement Disorder (PLMD) as well as the precise role of melatonin in human physiology remains poorly understood. Inspired by a single case observation we performed the presented study in order to obtain first evidence for the hypothesis that exogenous melatonin would decrease PLM's and thereby improves symptoms of PLMD patients.

DESIGN: N/A.

SETTING: N/A.

PATIENTS/PARTICIPANTS: Nine patients with first time diagnosis of PLMD without RLS were treated over a six-week period with 3 mg melatonin, taken between 10 and 11 p.m.

INTERVENTIONS: N/A.

RESULTS: Melatonin improved well-being in 7 of the 9 patients. Polysomnography, performed prior and at the end of melatonin treatment, demonstrated a significant reduction of investigated movement parameters, such as PLMs, PLM index, PLMs with arousals and PLM-arousal index. Actigraphy, measured over 14 nights prior and during the last 14 days of melatonin treatment, showed a significant reduction in movement rate and minutes with movements during Time in Bed.

CONCLUSIONS: The temporal distribution of PLMs, as well as the coupling of PLMs with the phase position of circadian temperature curve, suggest an involvement of the circadian timing system in the pathophysiology of PLMD. Locomotor activity in animals clearly exhibits a circadian pattern and can be strongly influenced by exogenous melatonin. Results suggest a chronobiotic effect of exogenous melatonin in PLMD. More specifically, we hypothesize that the mode of action of melatonin in the presented PLMD patients might have been an increase of output-amplitude of the circadian timing system, thereby enhancing the circadian rhythmicity of locomotor activity with a reduction of sleep motor activity.