A Comprehensive Review of Current and Emerging Treatments for Narcolepsy Type 1

Narcolepsy Type 1 (NT1) is a rare chronic neurological disorder characterized by core clinical manifestations such as excessive daytime sleepiness (EDS), cataplexy, sleep paralysis (SP), hypnagogic and hypnopompic hallucinations (HHs), and disrupted nocturnal sleep (DNS). Patients often experience comorbidities, including cognitive impairment, psychiatric disorders, and metabolic syndrome, necessitating lifelong management. Current therapeutic approaches primarily involve pharmacologic treatments for symptomatic relief, supplemented by non-pharmacologic interventions aimed at alleviating EDS and cataplexy. However, existing therapies are limited in efficacy and do not offer a cure. In recent years, a deeper understanding of the central role played by the orexin (hypocretin) system in the pathogenesis of NT1 has led to breakthrough advances in mechanism-based therapies targeting this pathway. Notably, selective orexin-2 receptor (OX2R) agonists such as TAK-861 have shown remarkable efficacy in Phase II/III clinical trials, holding the potential to fundamentally reshape the NT1 treatment landscape. This review systematically outlines current treatment options for NT1, with a focus on management strategies for atypical symptoms and special populations. It also highlights emerging therapeutic directions-including orexin-targeted agents, immunotherapies, and orexin cell/gene treatments-along with their future development.