Antipsychotics and Sleep Architecture: Where Does Lurasidone Fit?

Sleep disturbances are highly prevalent in schizophrenia, bipolar disorder, and other psychiatric disorders and are associated with increased symptom burden, impaired functioning, and reduced quality of life. Although second-generation antipsychotics frequently affect sleep, their effects vary according to receptor-binding profile and should not be viewed solely as a consequence of sedation. Lurasidone is distinguished by antagonism at D2, 5-HT2A, and 5-HT7 receptors with minimal affinity for histamine H1 and muscarinic M1 receptors, a pharmacologic profile associated with relatively low intrinsic sedation. This narrative review summarizes the neurobiology of sleep, examines receptor-based hypotheses through which lurasidone may influence sleep, and reviews the available preclinical and clinical evidence regarding its effects on sleep continuity and sleep architecture. Limited human evidence suggests that lurasidone may improve objective measures of sleep continuity, whereas preclinical findings suggest possible effects on rapid eye movement and non-rapid eye movement sleep. However, direct human evidence supporting modification of sleep architecture remains limited, and existing phase-advance data should not be interpreted as evidence of altered circadian physiology. Dedicated sleep studies remain few, and long-term data using polysomnography, actigraphy, circadian biomarkers, and validated measures of daytime functioning are lacking. Further comparative studies are needed to determine whether lurasidone provides clinically meaningful sleep-related benefits beyond improvements attributable to treatment of the underlying psychiatric disorder.