Fig. 10.

Available behavioral and pharmacological strategies to restore circadian rhythms in patients. The timing and regularity of bright light exposure, physical exercise, social and family life, and sleep-wake routine affect the function of the central clock, whereas the fasting-feeding schedule impacts on metabolism-linked peripheral clocks. Novel synthetic agonists or modified-release formulations of the hormones melatonin (e.g., Ramelteon, Tasimelteon, Agomelanine) and cortisol (e.g., delayed-release prednisone) can be used to target the central clock, as well as the peripheral oscillators in tissues equipped with the specific receptors. Several drugs used to treat psychiatric conditions, thus affecting neuronal function in the central nervous system, such as lithium, selective serotonin-uptake inhibitors, anxiolytic and hypnotic GABA agonists, or novel sleep inducers like the orexin-antagonist Suvorexant, can directly or indirectly modulate the function of the central clock, because SCN neurons are equipped with receptors of these drugs, or receive neuronal input from other brain areas affected by these drug classes. Finally, recent small molecules targeting core proteins of the circadian molecular clock modify their activity and thus impact circadian functions; these include REV-ERB agonist, CK1 inhibitor, SIRT1 agonist, and CRY activator.