Lemborexant for the Treatment of Residual Insomnia in Major Depressive Disorder (MDD)

Summary

The goal of this clinical trial is to learn if Lemborexant works to treat residual insomnia in adults with depression that is being treated. It will also learn about how practical, tolerable, and effective Lemborexant is. The main questions it aims to answer are: * Does Lemborexant help participants improve sleep and reduce insomnia symptoms? * How practical is it to use Lemborexant (how many participants join, drop out, and follow the study rules)? How do participants feel about using it (based on surveys and interviews)? Researchers will compare Lemborexant to a placebo (a look-alike substance that contains no drug) to see if Lemborexant works to treat residual insomnia in adequately treated major depressive disorder. Participants will: * Take Lemborexant or a placebo every day for 6 weeks (2 weeks at 5 mg then 4 weeks at 10 mg) * Complete clinical assessments and in-person study visits * Maintain a digital sleep diary and complete daily and weekly self-report ecological momentary assessments (EMAs) * Use a wearable device which will be used to collect and monitor physiological data

Timeline

Start

2024-09-25

Primary completion

2027-12

Completion

2028-04

Publications

• Background Manual (on) Transcription: Transcription Conventions, Software Guides and Practical Hints for Qualitative Researchers. 3. Engl. Ed., January 2015. Marburg: dr. dresing et pehl GmbH; 2015.
• Background Wilson EB. Probable Inference, the Law of Succession, and Statistical Inference. J Am Stat Assoc. 1927;22: 209-212. doi:10.1080/01621459.1927.10502953
• Background Topp CW, Ostergaard SD, Sondergaard S, Bech P. The WHO-5 Well-Being Index: a systematic review of the literature. Psychother Psychosom. 2015;84(3):167-76. doi: 10.1159/000376585. Epub 2015 Mar 28.
• Background Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
• Background Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999 Nov 10;282(18):1737-44. doi: 10.1001/jama.282.18.1737.
• Background Bang H, Flaherty SP, Kolahi J, Park J. Blinding assessment in clinical trials: A review of statistical methods and a proposal of blinding assessment protocol. Clin Res Regul Aff. 2010;27: 42-51. doi:10.3109/10601331003777444
• Background Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.
• Background Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.
• Background HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.
• Background Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 Jul;2(4):297-307. doi: 10.1016/s1389-9457(00)00065-4.
• Background Edward KL, Garvey L, Aziz Rahman M. Wearable activity trackers and health awareness: Nursing implications. Int J Nurs Sci. 2020 Mar 25;7(2):179-183. doi: 10.1016/j.ijnss.2020.03.006. eCollection 2020 Apr 10.
• Background Lee S, Kim H, Park MJ, Jeon HJ. Current Advances in Wearable Devices and Their Sensors in Patients With Depression. Front Psychiatry. 2021 Jun 17;12:672347. doi: 10.3389/fpsyt.2021.672347. eCollection 2021.
• Background Ahmed A, Aziz S, Alzubaidi M, Schneider J, Irshaidat S, Abu Serhan H, Abd-Alrazaq AA, Solaiman B, Househ M. Wearable devices for anxiety & depression: A scoping review. Comput Methods Programs Biomed Update. 2023;3:100095. doi: 10.1016/j.cmpbup.2023.100095. Epub 2023 Jan 30.
• Background Martin J, Rueda A, Lee GH, Tassone VK, Park H, Ivanov M, Darnell BC, Beavers L, Campbell DM, Nguyen B, Torres A, Jung H, Lou W, Nazarov A, Ashbaugh A, Kapralos B, Litz B, Jetly R, Dubrowski A, Strudwick G, Krishnan S, Bhat V. Digital Interventions to Understand and Mitigate Stress Response: Protocol for Process and Content Evaluation of a Cohort Study. JMIR Res Protoc. 2024 May 6;13:e54180. doi: 10.2196/54180.
• Background Eisai Inc. PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION: DAYVIGO Lemborexant Tablet Tablet, 5 mg, 10 mg, Oral. 2023.
• Background Uzun S, Kozumplik O, Jakovljevic M, Sedic B. Side effects of treatment with benzodiazepines. Psychiatr Danub. 2010 Mar;22(1):90-3.
• Background Yardley J, Karppa M, Inoue Y, Pinner K, Perdomo C, Ishikawa K, Filippov G, Kubota N, Moline M. Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Sleep Med. 2021 Apr;80:333-342. doi: 10.1016/j.sleep.2021.01.048. Epub 2021 Feb 1.
• Background Eisai Inc. U.S. FDA APPROVES EISAI'S DAYVIGOTM (LEMBOREXANT) FOR TREATMENT OF INSOMNIA IN ADULT PATIENTS. 2019. Available: https://www.eisai.com/news/2019/news201993.html#:~:text=IN%20ADULT%20PATIENTS-,U.S.%20FDA%20APPROVES%20EISAI'S%20DAYVIGO%E2%84%A2%20(LEMBOREXANT)%20FOR%20TREATMENT%20OF,OF%20MORE%20THAN%202%2C000%20PATIENTS
• Background Regulatory Decision Summary for Dayvigo. Government of Canada; 2024. Available: https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS00757
• Background Nakamura M, Nagamine T. Neuroendocrine, Autonomic, and Metabolic Responses to an Orexin Antagonist, Suvorexant, in Psychiatric Patients with Insomnia. Innov Clin Neurosci. 2017 Apr 1;14(3-4):30-37. eCollection 2017 Mar-Apr.
• Background Kuriyama A, Tabata H. Suvorexant for the treatment of primary insomnia: A systematic review and meta-analysis. Sleep Med Rev. 2017 Oct;35:1-7. doi: 10.1016/j.smrv.2016.09.004. Epub 2016 Oct 28.
• Background Michelson D, Snyder E, Paradis E, Chengan-Liu M, Snavely DB, Hutzelmann J, Walsh JK, Krystal AD, Benca RM, Cohn M, Lines C, Roth T, Herring WJ. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014 May;13(5):461-71. doi: 10.1016/S1474-4422(14)70053-5. Epub 2014 Mar 27.
• Background Triantafillou S, Saeb S, Lattie EG, Mohr DC, Kording KP. Relationship Between Sleep Quality and Mood: Ecological Momentary Assessment Study. JMIR Ment Health. 2019 Mar 27;6(3):e12613. doi: 10.2196/12613.
• Background Fortuyn HA, Lappenschaar MA, Furer JW, Hodiamont PP, Rijnders CA, Renier WO, Buitelaar JK, Overeem S. Anxiety and mood disorders in narcolepsy: a case-control study. Gen Hosp Psychiatry. 2010 Jan-Feb;32(1):49-56. doi: 10.1016/j.genhosppsych.2009.08.007. Epub 2009 Oct 1.
• Background Grafe LA, Bhatnagar S. Orexins and stress. Front Neuroendocrinol. 2018 Oct;51:132-145. doi: 10.1016/j.yfrne.2018.06.003. Epub 2018 Jun 19.
• Background Salomon RM, Ripley B, Kennedy JS, Johnson B, Schmidt D, Zeitzer JM, Nishino S, Mignot E. Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Biol Psychiatry. 2003 Jul 15;54(2):96-104. doi: 10.1016/s0006-3223(02)01740-7.
• Background Schmidt FM, Brugel M, Kratzsch J, Strauss M, Sander C, Baum P, Thiery J, Hegerl U, Schonknecht P. Cerebrospinal fluid hypocretin-1 (orexin A) levels in mania compared to unipolar depression and healthy controls. Neurosci Lett. 2010 Oct 8;483(1):20-2. doi: 10.1016/j.neulet.2010.07.038. Epub 2010 Jul 22.
• Background Brundin L, Bjorkqvist M, Petersen A, Traskman-Bendz L. Reduced orexin levels in the cerebrospinal fluid of suicidal patients with major depressive disorder. Eur Neuropsychopharmacol. 2007 Sep;17(9):573-9. doi: 10.1016/j.euroneuro.2007.01.005. Epub 2007 Mar 7.
• Background Nollet M, Leman S. Role of orexin in the pathophysiology of depression: potential for pharmacological intervention. CNS Drugs. 2013 Jun;27(6):411-22. doi: 10.1007/s40263-013-0064-z.
• Background Nollet M, Gaillard P, Tanti A, Girault V, Belzung C, Leman S. Neurogenesis-independent antidepressant-like effects on behavior and stress axis response of a dual orexin receptor antagonist in a rodent model of depression. Neuropsychopharmacology. 2012 Sep;37(10):2210-21. doi: 10.1038/npp.2012.70. Epub 2012 Jun 20.
• Background Nollet M, Gaillard P, Minier F, Tanti A, Belzung C, Leman S. Activation of orexin neurons in dorsomedial/perifornical hypothalamus and antidepressant reversal in a rodent model of depression. Neuropharmacology. 2011 Jul-Aug;61(1-2):336-46. doi: 10.1016/j.neuropharm.2011.04.022. Epub 2011 Apr 23.
• Background Scammell TE. Narcolepsy. N Engl J Med. 2015 Dec 31;373(27):2654-62. doi: 10.1056/NEJMra1500587. No abstract available.
• Background Yoshida Y, Fujiki N, Nakajima T, Ripley B, Matsumura H, Yoneda H, Mignot E, Nishino S. Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities. Eur J Neurosci. 2001 Oct;14(7):1075-81. doi: 10.1046/j.0953-816x.2001.01725.x.
• Background Pae CU, Tharwani H, Marks DM, Masand PS, Patkar AA. Atypical depression: a comprehensive review. CNS Drugs. 2009 Dec;23(12):1023-37. doi: 10.2165/11310990-000000000-00000.
• Background Alijanpour S, Khakpai F, Ebrahimi-Ghiri M, Zarrindast MR. Co-administration of the low dose of orexin and nitrergic antagonists induces an antidepressant-like effect in mice. Biomed Pharmacother. 2019 Jan;109:589-594. doi: 10.1016/j.biopha.2018.10.033. Epub 2018 Nov 3.
• Background Berridge CW, Espana RA. Hypocretins: waking, arousal, or action? Neuron. 2005 Jun 2;46(5):696-8. doi: 10.1016/j.neuron.2005.05.016.
• Background Nutt D, Wilson S, Paterson L. Sleep disorders as core symptoms of depression. Dialogues Clin Neurosci. 2008;10(3):329-36. doi: 10.31887/DCNS.2008.10.3/dnutt.
• Background Shariq AS, Rosenblat JD, Alageel A, Mansur RB, Rong C, Ho RC, Ragguett RM, Pan Z, Brietzke E, McIntyre RS. Evaluating the role of orexins in the pathophysiology and treatment of depression: A comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:1-7. doi: 10.1016/j.pnpbp.2018.12.008. Epub 2018 Dec 18.
• Background Health Quality Ontario. Psychotherapy for Major Depressive Disorder and Generalized Anxiety Disorder: A Health Technology Assessment. Ont Health Technol Assess Ser. 2017 Nov 13;17(15):1-167. eCollection 2017.

Drugs

Indications