Pharmacological Management of Sleep–Wake Disturbances in Delirium

Abstract Delirium is a heterogeneous syndrome primarily characterized by fluctuations in attention and awareness. Sleep–wake disturbances are a common and significant feature of delirium and can manifest as circadian rhythm inversion, sleep fragmentation, and reduced rapid eye movement (REM) and slow‐wave sleep. Some literature suggests that the relationship between sleep disruption and delirium is reciprocal wherein the two reinforce one another and may share an underlying etiology. As there are no FDA‐approved medications for delirium or delirium‐related sleep disturbances, management is primarily focused on addressing underlying medical concerns and promoting physiologic circadian patterns with non‐pharmacological behavioral interventions. In practice, however, medications are often used, albeit with limited evidence to support their use. This literature review explores the pharmacology and pharmacokinetics of several medications with literature investigating their use in delirium: melatonin, ramelteon, dual orexin receptor antagonists (DORAs), and dexmedetomidine. Current evidence suggests a possible benefit of ramelteon or melatonin, dexmedetomidine for patients in the ICU setting, and DORAs as therapeutic options for the re‐regulation of sleep–wake cycle disruption in delirium. We discuss pertinent pharmacokinetic and pharmacodynamic factors that may influence clinical decision‐making regarding these interventions.