Phase-shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men

Objective Older adults are less responsive to the phase-shifting effects of light than younger subjects and may have difficulties adapting to abrupt time shifts. This study aims to determine whether the potent melatonin agonist agomelatine (S-20098) is capable of phase-shifting overt circadian rhythms in older adults. Subjects and design Eight healthy elderly men participated in a double-blind, two-period, cross-over study of 15 days of daily administration of either agomelatine (50 mg) or placebo at 1830 h. Measurements At the end of each treatment period, the 24-h profiles of body temperature and of the plasma levels of GH, PRL, cortisol and TSH were collected and sleep was monitored polygraphically. Results Phase-advances, averaging nearly 2 h, were observed for the temperature profile and for the variables characterizing the temporal organization of cortisol secretion following agomelatine administration. A similar trend was observed for the circadian rise of plasma TSH. There was no effect of agomelatine on any of the sleep variables. Agomelatine stimulated GH secretion during the wake period and was associated with a transient elevation of PRL levels. Conclusions Melatonin agonists such as agomelatine may be useful to phase-shift at least some overt circadian rhythms in older adults.