Brooks S, Jacobs GE, de Boer P, Kent JM, Van Nueten L, van Amerongen G, Zuiker R, Kezic I, Luthringer R, van der Ark P, van Gerven JM, Drevets W (2019) The selective orexin-2 receptor antagonist seltorexant improves sleep: an exploratory double-blind, placebo controlled, crossover study in antidepressant-treated major depressive disorder patients with persistent insomnia. J Psychopharmacol 33:202–209
Article CAS PubMed Google Scholar
Chieffi S, Carotenuto M, Monda V, Valenzano A, Villano I, Precenzano F, Tafuri D, Salerno M, Filippi N, Nuccio F, Ruberto M, De Luca V, Cipolloni L, Cibelli G, Mollica MP, Iacono D, Nigro E, Monda M, Messina G, Messina A (2017) Orexin system: the key for a healthy life. Front Physiol 8:357
Article PubMed PubMed Central Google Scholar
Citrome L, Gaynes BN, Goldberg JF, Ketter T, Murrough JW (2019) New mechanisms, new opportunities: Integrating novel antidepressants in the treatment of major depressive disorder. J Clin Psychiatry 80:TK18061AS2C
Connor KM, Ceesay P, Hutzelmann J, Snavely D, Krystal AD, Trivedi MH, Thase M, Lines C, Herring WJ, Michelson D (2017) Phase ii proof-of-concept trial of the orexin receptor antagonist filorexant (mk-6096) in patients with major depressive disorder. Int J Neuropsychopharmacol 20:613–618
Article CAS PubMed PubMed Central Google Scholar
Dale NC, Hoyer D, Jacobson LH, Pfleger KDG, Johnstone EKM (2022) Orexin signaling: a complex, multifaceted process. Front Cell Neurosci 16:812359
Article CAS PubMed PubMed Central Google Scholar
De Crescenzo F, D’Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A (2022) Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet 400:170–184
Fagan H, Jones E, Baldwin DS (2023) Orexin receptor antagonists in the treatment of depression: a leading article summarising pre-clinical and clinical studies. CNS Drugs 37:1–12
Article CAS PubMed Google Scholar
Fuller MC, Carlson SF, Grant C, Berry V, Ivancich M, Cornett EM, Kaye AM, Viswanath O, Urits I, Shekoohi S, Kaye AD (2024) A comprehensive review of lemborexant to treat insomnia. Psychopharmacol Bull 54:43–64
PubMed PubMed Central Google Scholar
James MH, Mahler SV, Moorman DE, Aston-Jones G (2017) A decade of orexin/hypocretin and addiction: where are we now? Curr Top Behav Neurosci 33:247–281
Article PubMed PubMed Central Google Scholar
Jiang M, Li H, Kong L (2024) Data mining and safety analysis of dual orexin receptor antagonists (doras): a real-world pharmacovigilance study based on the faers database. Front Pharmacol 15:1436405
Article CAS PubMed PubMed Central Google Scholar
Jindal RD, Thase ME (2004) Treatment of insomnia associated with clinical depression. Sleep Med Rev 8:19–30
Joshi K, Cambron-Mellott MJ, Costantino H, Pfau A, Jha MK (2023) The clinical, economic, and patient-centric burden of insomnia symptom severity in adults with major depressive disorder in the united states. Brain Behav 13:e3143
Article PubMed PubMed Central Google Scholar
Khairuddin S, Aquili L, Heng BC, Hoo TLC, Wong KH, Lim LW (2020) Dysregulation of the orexinergic system: a potential neuropeptide target in depression. Neurosci Biobehav Rev 118:384–396
Article CAS PubMed Google Scholar
Kupfer DJ, Thase ME (1983) The use of the sleep laboratory in the diagnosis of affective disorders. Psychiatr Clin North Am 6:3–25
Article CAS PubMed Google Scholar
Lee-Iannotti JK, Parish JM (2016) Suvorexant: a promising, novel treatment for insomnia. Neuropsychiatr Dis Treat 12:491–495
CAS PubMed PubMed Central Google Scholar
Malhi GS, Mann JJ (2018) Depression Lancet 392:2299–2312
Mesens S, Kezic I, Van Der Ark P, Etropolski M, Pandina G, Benes H, Savitz A, Drevets WC (2024) Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial. Mol Psychiatry
Meshkat S, Kwan ATH, Le GH, Wong S, Teopiz KM, Wang L, Rosenblat JD, Rhee TG, Cao B, McIntyre RS (2025) Efficacy of orexin antagonists for the management of major depressive disorder: a systematic review of randomized clinical trials. J Affect Disord 372:409–419
Article CAS PubMed Google Scholar
Mogavero MP, Silvani A, Lanza G, DelRosso LM, Ferini-Strambi L, Ferri R (2023) Targeting orexin receptors for the treatment of insomnia: from physiological mechanisms to current clinical evidence and recommendations. Nat Sci Sleep 15:17–38
Article PubMed PubMed Central Google Scholar
Muehlan C, Roch C, Vaillant C, Dingemanse J (2023) The orexin story and orexin receptor antagonists for the treatment of insomnia. J Sleep Res 32:e13902
Muehlan C, Vaillant C, Zenklusen I, Kraehenbuehl S, Dingemanse J (2020) Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders. Expert Opin Drug Metab Toxicol 16:1063–1078
Article CAS PubMed Google Scholar
Nierenberg AA (2015) Residual symptoms in depression: prevalence and impact. J Clin Psychiatry 76:e1480
Nollet M, Leman S (2013) Role of orexin in the pathophysiology of depression: potential for pharmacological intervention. CNS Drugs 27:411–422
Article CAS PubMed Google Scholar
Pan B, Ge L, Lai H, Hou L, Tian C, Wang Q, Yang K, Lu Y, Zhu H, Li M, Wang D, Li X, Zhang Y, Gao Y, Liu M, Ding G, Tian J, Yang K (2023) The comparative effectiveness and safety of insomnia drugs: a systematic review and network meta-analysis of 153 randomized trials. Drugs 83:587–619
Pizza F, Barateau L, Dauvilliers Y, Plazzi G (2022) The orexin story, sleep and sleep disturbances. J Sleep Res 31:e13665
Recourt K, de Boer P, Zuiker R, Luthringer R, Kent J, van der Ark P, Van Hove I, van Gerven J, Jacobs G, van Nueten L, Drevets W (2019) The selective orexin-2 antagonist seltorexant (jnj-42847922/min-202) shows antidepressant and sleep-promoting effects in patients with major depressive disorder. Transl Psychiatry 9:216
Article PubMed PubMed Central Google Scholar
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a star*d report. Am J Psychiatry 163:1905–1917
Sakurai T, Saito YC, Yanagisawa M (2021) Interaction between orexin neurons and monoaminergic systems. Front Neurol Neurosci 45:11–21
Salomon RM, Ripley B, Kennedy JS, Johnson B, Schmidt D, Zeitzer JM, Nishino S, Mignot E (2003) Diurnal variation of cerebrospinal fluid hypocretin-1 (orexin-a) levels in control and depressed subjects. Biol Psychiatry 54:96–104
Article CAS PubMed Google Scholar
Savitz A, Wajs E, Zhang Y, Xu H, Etropolski M, Thase ME, Drevets WC (2021) Efficacy and safety of seltorexant as adjunctive therapy in major depressive disorder: a phase 2b, randomized, placebo-controlled, adaptive dose-finding study. Int J Neuropsychopharmacol 24:965–976
Article CAS PubMed PubMed Central Google Scholar
Schwartz MD, Kilduff TS (2015) The neurobiology of sleep and wakefulness. Psychiatr Clin North Am 38:615–644
Article PubMed PubMed Central Google Scholar
Shariq AS, Rosenblat JD, Alageel A, Mansur RB, Rong C, Ho RC, Ragguett RM, Pan Z, Brietzke E, McIntyre RS (2019) Evaluating the role of orexins in the pathophysiology and treatment of depression: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry 92:1–7
Comments (0)