Orexinergic Receptor Antagonists as a New Therapeutic Target to Overcome Limitations of Current Pharmacological Treatment of Insomnia Disorder

Insomnia disorder is a common condition that is considered a risk factor for multiple physical and mental disorders, contributing to reduced quality of life and increased healthcare expenditures. Although cognitive behavioral therapy (CBT) is typically recommended as the primary intervention, its ac...

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Detalles Bibliográficos
Autores: Álamo González, Cecilio Francisco|||0000-0001-7652-7931, Saiz Ruiz, Jerónimo|||0000-0001-9625-167X, Zaragozá Arnáez, Cristina|||0000-0002-4768-6797
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:español
OAI Identifier:oai:ebuah.uah.es:10017/64374
Acceso en línea:http://hdl.handle.net/10017/64374
https://dx.doi.org/10.62641/aep.v52i2.1659
Access Level:acceso abierto
Palabra clave:Insomnia
Benzodiazepines
Orexin
DORAs
Daridorexant
Farmacia
Pharmacy
Descripción
Sumario:Insomnia disorder is a common condition that is considered a risk factor for multiple physical and mental disorders, contributing to reduced quality of life and increased healthcare expenditures. Although cognitive behavioral therapy (CBT) is typically recommended as the primary intervention, its accessibility is hindered by limited resources, prompting the prevalent use of pharmacological interventions as the primary treatment in clinical settings. This study reviews the benefits and risks of current pharmacological treatments for insomnia, with special reference to the orexinergic system as a novel therapeutic target for treatment. The prescription of GABAergic mechanism enhancers (benzodiazepine (BZD) and "Z drugs") has shown efficacy in short-term insomnia treatment (less than 4 weeks), however, concerns arise regarding their longterm effectiveness, unfavorable tolerability and safety profiles, including the potential for dependency. Drugs with antihistamine properties, including certain antidepressants and antipsychotics, exhibit short-term efficacy but have documented tolerability limitations, especially in the elderly. The use of melatonin, available in various formulations, lacks comprehensive long-term data. Dual orexin receptor antagonists (DORAs) such as daridorexant, lemborexant, and suvorexant, represent a novel approach to insomnia treatment by inhibiting wakefulness rather than enhancing sedation. As the only DORA approved for insomnia treatment by the European Medicines Agency (EMA) and Food and Drug Administration (FDA), daridorexant has demonstrated sustained efficacy over a 12 -month period, improving nocturnal sleep parameters and daytime functionality, with a favorable safety and tolerability profile.