Insomnia Pharmacotherapy: CBT-I and Medication Selection

Insomnia disorder is defined as dissatisfaction with sleep quantity or quality associated with difficulty initiating sleep, maintaining sleep, or early-morning awakening, occurring at least 3 nights per week for at least 3 months, causing clinically significant distress or functional impairment, and not better explained by another sleep disorder, substance, or medical condition. Normal sleep architecture involves cycling through NREM (non-rapid eye movement) stages N1, N2, and N3 (slow-wave/deep sleep) and REM (rapid eye movement) sleep in approximately 90-minute ultradian cycles, with 4-6 cycles per night. The sleep-wake cycle is regulated by two processes: Process C (circadian — the suprachiasmatic nucleus of the hypothalamus responds to light input via the retinohypothalamic tract, coordinating the 24-hour circadian rhythm through melatonin secretion from the pineal gland in darkness) and Process S (homeostatic sleep pressure — adenosine accumulates in the basal forebrain during wakefulness, increasing sleep drive; caffeine blocks adenosine receptors, counteracting this drive). The neurobiology of insomnia involves hyperarousal of the ascending reticular activating system (ARAS). The wake-promoting system includes orexin/hypocretin neurons (lateral hypothalamus), histaminergic neurons (tuberomammillary nucleus), noradrenergic neurons (locus coeruleus), serotonergic...