Circadian aspects in nonpharmacologic and pharmacologic treatment of insomnia.

Insomnia disorder is a frequent sleep disorder leading to significant health and economic consequences. It has been proposed that individuals with insomnia may experience compromised deactivation systems of arousal, leading to a chronic state of hyperactivation of arousal known as hyperarousal, along with instability in the flip-flop system. Such disruptions may have a primarily impact on the sleep homeostatic drive process. Insomnia may indeed be associated with a disruption in the body's internal clock, known as chronodisruption. Despite the differentiation established in diagnostic nosology between insomnia disorder and circadian rhythm disorders, there is a significant body of evidence suggesting a complex interplay and frequent co-occurrence between these two conditions. In particular, circadian factors can predispose individuals to insomnia disorders, as well as precipitate and perpetuate their symptoms. Accordingly numerous pieces of evidence suggest that both pharmacologic and nonpharmacologic options for treating insomnia can have a resynchronization effect on circadian rhythms. The first-line treatment for chronic insomnia, according to current guidelines, is cognitive behavioral therapy for insomnia while pharmacologic interventions comprise of benzodiazepine receptor agonists also known as Z-drugs and short- to medium-acting benzodiazepines, melatonergic agonists such as ramelteon and melatonin 2mg prolonged release, and dual orexin receptor antagonists such as daridorexant, suvorexant, and lemborexant. At the same time, certain therapies recommended for circadian rhythm disorders can be utilized as adjunctive treatments for insomnia. Therefore, this chapter will discuss the circadian aspects of insomnia disorder and of its therapeutic approach. Furthermore, the effects of chronobiologic interventions, recommended for the treatment of circadian rhythm sleep-wake disorders, will be examined in individuals afflicted with chronic insomnia.