Chapter 41: Sleep Disorders – Pharmacologic Approaches

Sleep Disorders – Pharmacologic Approaches begins by outlining the fundamental physiology of sleep, differentiating between NREM (Stages I–IV) and REM cycles, and noting the significant health and economic impact associated with sleep disruption. Insomnia is defined by persistent difficulty with sleep, classified into chronic and short-term disorders, often stemming from psychological or physiological hyperarousal. Pharmacologic treatment strategies for insomnia are cautious, emphasizing the minimal dose for the shortest duration, with goals focused on enhancing sleep quality and reducing daytime impairment. Key treatment classes covered include Benzodiazepines (BZDs) and Benzodiazepine Receptor Agonists (BZRAs) (e.g., zolpidem, zaleplon, eszopiclone), which modulate GABA receptors to induce sedation, though the risk of dependency and complex sleep behaviors is highlighted. Newer options discussed are Orexin Receptor Antagonists (DORAs), such as suvorexant and lemborexant, which block wakefulness signals, and Melatonin Receptor Agonists (ramelteon), which assist in circadian rhythm regulation. The discussion then shifts to Willis–Ekbom Disease (WED) (RLS), a sensory-motor disorder linked to deficiencies in iron, dopaminergic abnormalities, and glutamate. First-line therapy for daily RLS/WED symptoms includes non-ergot dopamine agonists (pramipexole, rotigotine) and the approved anticonvulsant, gabapentin enacarbil, with attention paid to the risk of augmentation. Finally, the chapter addresses narcolepsy, a lifelong disorder resulting from hypocretin deficits, characterized by excessive daytime sleepiness (EDS) and often cataplexy. Treatment agents aim to promote wakefulness and suppress REM-related symptoms, utilizing classic psychostimulants like Modafinil and Methylphenidate, the CNS depressant Sodium Oxybate (Xyrem), and newer agents like the Histamine H3 Antagonist/Inverse Agonist (pitolisant) and the Dopamine–Norepinephrine Reuptake Inhibitor (solriamfetol). The text stresses the importance of individualized therapy and monitoring across all patient populations, including geriatric and pediatric cases.