Safety, efficacy, and potential clinical application of nivasorexant, a novel orexin receptor antagonist, in psychiatry: A systematic review

ABSTRACT Orexin A and orexin B are neuropeptides that play an important role in regulating physiological functions such as stress response, reward, energy, and arousal. Orexin receptor antagonists (ORAs), such as nivasorexant, are a new class of medications targeting the orexin system. Nivasorexant is a selective orexin-1 receptor antagonist (OX1R) that was developed to avoid dual receptor antagonists. We aimed to conduct this systematic review to evaluate the safety and efficacy of nivasorexant and to explore the potential clinical uses in psychiatry. Relevant databases were searched to identify studies focused on nivasorexant’s pharmacokinetics, pharmacodynamics, safety, efficacy, and clinical uses in humans. Out of 34 articles identified, five articles were included. Preclinical evidence suggested a promising role for nivasorexant in modulating compulsive behaviors due to its high selectivity for OX1R and lack of significant sedation. Clinical investigations have provided insights into its pharmacokinetic profile and generally favorable safety. While initial efficacy findings for a specific psychiatric indication were not definitively met, exploratory analyses suggest that patient characteristics might influence treatment outcomes. Furthermore, nivasorexant’s metabolic profile indicates potential for drug interactions, requiring careful consideration in clinical practice. Nivasorexant’s potential for addressing disorders is characterized by dysregulated reward processing, where maintaining alertness is desirable, based on its selective mechanism and tolerability. However, this review is limited by the current volume of clinical data, the scope of studies conducted, and the generalizability of findings across diverse patient populations. Further rigorous clinical validation is needed to fully ascertain its therapeutic potential and optimal application in psychiatry.