Daridorexant for the Treatment of Insomnia
Purpose of Review
Insomnia is a complex sleeping disorder that affects the lives of many individuals worldwide. Insomnia often occurs in the presence of coexisting comorbidities making it a complex disorder that requires a multifactorial approach to therapy. First-line therapy is cognitive-behavioral therapy for insomnia (CBT-I). Pharmacotherapy for insomnia falls into four classes based on mechanism of action: benzodiazepine receptor agonists (BZRAs), histamine receptor antagonists, melatonin receptor agonists, and dual orexin receptor antagonists (DORAs).
Recent Findings
Daridorexant is a dual orexin type 1 and types 2 (OX1 and OX2) receptor antagonist that was recently approved by the US FDA for the treatment of adults suffering from insomnia. It was shown to be effective in reducing insomnia symptoms, increasing daytime functioning, and improving the overall quality of sleep. Daridorexant offers patients relief from insomnia while avoiding the severe side effects and dependency issues of traditional treatments like benzodiazepines and sedatives.
Summary
In this article, we review the most recent data on insomnia treatments and summarize the safety and efficacy of daridorexant in treating insomnia.
1. Sateia MJ. International Classification of Sleep Disorders-Third Edition. Chest.2014;146(5):1387-1394. doi:10.1378/chest.14-0970
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association;2013. doi:10.1176/appi.books.9780890425596
3. Riemann D, Benz F, Dressle RJ,et al. Insomnia disorder: state of the science and challenges for the future. Journal of Sleep Research.2022;31(4). doi:10.1111/jsr.13604
4. Herring WJ, Roth T, Krystal AD, Michelson D.Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications. J Sleep Res.2019;28(2).doi:10.1111/jsr.12782
5. Dopheide JA. Insomnia overview: epidemiology,pathophysiology, diagnosis and monitoring, and nonpharmacologic therapy. Am J Manag Care.2020;26:S76-S84.doi:10.37765/ajmc.2020.42769
6. Qaseem A, Kansagara D, Forciea MA,Cooke M,Denberg TD. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med.2016;165(2):125. doi:10.7326/m15-2175
7. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN,Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of Clinical Sleep Medicine.2017;13(2):307-349. doi:10.5664/jcsm.6470
8. Markham A.Daridorexant:First Approval.Drugs.2022;82(5):601-607.doi:10.1007/s40265-022-01699-y
9. Roth T, Coulouvrat C, Hajak G,et al. Prevalence and Perceived Health Associated with Insomnia Based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, Second Edition Criteria: Results from the America Insomnia Survey. Biological Psychiatry.2011;69(6):592-600.doi:10.1016/j.biopsych.2010.10.023
10. Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Medicine Reviews.2002;6(2):97-111.doi:10.1053/smrv.2002.0186
11. Ford ES, Wheaton AG, Cunningham TJ,Giles WH,Chapman DP,Croft JB. Trends in outpatient visits for insomnia, sleep apnea, and prescriptions for sleep medications among US adults: findings from the National Ambulatory Medical Care survey 1999-2010.Sleep.2014;37(8):1283-1293. doi:10.5665/sleep.3914
12. Morin CM, LeBlanc M, Bélanger L, Ivers H,Mérette C, Savard J. Prevalence of Insomnia and its Treatment in Canada. Can J Psychiatry.2011;56(9):540-548. doi:10.1177/070674371105600905
13. Ohayon MM, Reynolds CF III. Epidemiological and clinical relevance of insomnia diagnosis algorithms according to the DSM-IV and the International Classification of Sleep Disorders(ICSD).Sleep Medicine.2009;10(9):952-960. doi:10.1016/j.sleep.2009.07.008
14. Walsh JK, Coulouvrat C, Hajak G,et al. Nighttime Insomnia Symptoms and Perceived Health in the America Insomnia Survey(AIS). Sleep.2011;34(8):997-1011. doi:10.5665/sleep.1150
15. Olfson M, Wall M, Liu SM, Morin CM, Blanco C.Insomnia and Impaired Quality of Life in the United States.J Clin Psychiatry.2018;79(5).doi:10.4088/jcp.17m12020
16. Ford DE. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA: The Journal of the American Medical Association. 1989;262:1479-1484.
17. Wickwire EM, Tom SE, Scharf SM, Vadlamani A,Bulatao IG, Albrecht JS. Untreated insomnia increases all-cause health care utilization and costs among Medicare beneficiaries. Sleep.2019;42(4).doi:10.1093/sleep/zsz007
18. Levenson JC, Kay DB, Buysse DJ.The Pathophysiology of Insomnia. Chest.2015;147(4):1179-1192. doi:10.1378/chest.14-1617
19. Riemann D, Benz F, Dressle RJ, et al. Insomnia disorder: State of the science and challenges for the future. Journal of Sleep Research.2022;31(4). doi:10.1111/jsr.13604
20. van Someren EJW. Brain mechanisms of insomnia: new perspectives on causes and consequences. Physiological Reviews.2021;101(3):995-1046.doi:10.1152/physrev.00046.2019
21. Palagini L, Hertenstein E, Riemann D, Nissen C.Sleep, insomnia and mental health. Journal of Sleep Research.2022;31(4). doi:10.1111/jsr.13628
22. Saper CB, Fuller PM,Pedersen NP,Lu J,Scammell TE. Sleep State Switching. Neuron.2010;68(6):1023-1042.doi:10.1016/j.neuron.2010.11.032
23. Fuller PM, Gooley JJ, Saper CB. Neurobiology of the Sleep-Wake Cycle: Sleep Architecture, Circadian Regulation, and Regulatory Feedback. J Biol Rhythms.2006;21(6):482-493. doi:10.1177/0748730406294627
24. Bonnet MH, Arand DL. Hyperarousal and insomnia: State of the science. Sleep MedicineReviews.2010;14(1):9-15.doi:10.1016/j.smrv.2009.05.002
25. Winkelman JW. Insomnia Disorder. N Engl J Med.2015;373(15):1437-1444. doi:10.1056/nejmcp1412740
26. Spielman AJ, Caruso LS, Glovinsky PB.A behavioral perspective on insomnia treatment.Psychiatr Clin North Am.1987;10(4):541-553.doi:10.1016/s0193-953x(18)30532-x
27. Drake CL, Pillai V, Roth T. Stress and sleep reactivity: a prospective investigation of the stress-diathesis model of insomnia. Sleep.2014;37(8):1295-1304. doi:10.5665/sleep.3916
28. Drake CL, Cheng P, Almeida DM,Roth T.Familial Risk for Insomnia Is Associated With Abnormal Cortisol Response to Stress. Sleep.2017;40(10). doi:10.1093/sleep/zsx143
29. Stein MB, McCarthy MJ, Chen CY,et al. Genome-wide analysis of insomnia disorder. Mol Psychiatry.2018;23(11):2238-2250.doi:10.1038/s41380-018-0033-5
30. Ohayon MM, Roth T. Place of chronic insomnia in the course of depressive and anxiety disorders.Journal of Psychiatric Research. 2003;37(1):9-15. doi:10.1016/s0022-3956(02)00052-3
31. A.S.D.A.absm.org/PDF/ICSD.& 1997,undefined. International classification of sleep disorders. Revised: diagnostic and coding manual. http://ci.nii.ac.jp
32. Bhaskar S, Hemavathy D, Prasad S. Prevalence of chronic insomnia in adult patients and its correlation with medical comorbidities. J Family Med Prim Care.2016;5(4):780. doi:10.4103/2249-4863.201153
33. Staner L. Comorbidity of insomnia and depression. Sleep Medicine Reviews.2010;14(1):35-46.doi:10.1016/j.smrv.2009.09.003
34. Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH,Riedel BW, Bush AJ. Comorbidity of Chronic Insomnia With Medical Problems. Sleep.2007;30(2):213-218.doi:10.1093/sleep/30.2.213
35. Overview of the treatment of insomnia in adults-UpToDate. https://www.uptodate.com/contents/overview-of-the-treatment-of-insomnia-in-adults
36. Jacobs GD, Pace-Schott EF, Stickgold R, Otto MW.Cognitive Behavior Therapy and Pharmacotherapy for Insomnia: A Randomized Controlled Trial and Direct Comparison. Arch Intern Med.2004;164(17):1888. doi:10.1001/archinte.164.17.1888
37. van Straten A, van der Zweerde T, Kleiboer A,Cuijpers P, Morin CM, Lancee J. Cognitive and behavioral therapies in the treatment of insomnia: A meta-analysis. Sleep Med Rev.2018;38:3-16.doi:10.1016/j.smrv.2017.02.001
38. Ayabe N, Okajima I, Nakajima S,et al.Effectiveness of cognitive behavioral therapy for pharmacotherapy-resistant chronic insomnia: a multi-center randomized controlled trial in Japan.Sleep Medicine.2018;50:105-112. doi:10.1016/j.slee p.2018.05.038
39. Rios P, Cardoso R,Morra D,et al. Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews. Syst Rev.2019;8(1).doi:10.1186/s13643-019-1163-9
40. Grandner MA, Perlis ML. Pharmacotherapy for Insomnia Disorder in Older Adults. JAMA NetwOpen.2019;2(12):e1918214. doi:10.1001/jamanetworkopen.2019.18214
41. Schmitz A. Benzodiazepine use, misuse, and abuse: A review. Mental Health Clinician.2016;6(3):120-126.doi:10.9740/mhc.2016.05.120
42. Crowe SF, Stranks EK. The Residual Medium and Long-term Cognitive Effects of Benzodiazepine Use:An Updated Meta-analysis. Archives of Clinical Neuropsychology.2018;33(7):901-911.doi:10.1093/arcclin/acx120
43. Fluyau D, Revadigar N, Manobianco BE.Challenges of the pharmacological management of benzodiazepine withdrawal, dependence, and discontinuation. Therapeutic Advances in Psychopharmacology.2018;8(5):147-168.doi:10.1177/2045125317753340
44. Dauvilliers Y,Zammit G,Fietze I,et al.Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder. Ann Neurol.2020;87(3):347-356. doi:10.1002/ana.25680
45. Markham A. Daridorexant: First Approval. Drugs.2022;82(5):601-607. doi:10.1007/s40265-022-01699-y
46. Markham A. Daridorexant: First Approval. Drugs.2022;82(5):601-607. doi:10.1007/s40265-022-01699-y
47. Molano JRV. Daridorexant: A new medication for insomnia in older adults? Neurology.2020;94(21):e2287-e2289. doi:10.1212/wnl.0000000000009489
48. fda,cder.HIGHLIGHTS OF PRESCRIBING INFORMATION.
49. Herring WJ, Roth T, Krystal AD, Michelson D.Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications. J Sleep Res. 2019;28(2).doi:10.1111/jsr.12782
50. Dauvilliers Y, Zammit G, Fietze I, et al.Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder. Ann Neurol.2020;87(3):347-356. doi:10.1002/ana.25680
51. Roch C, Bergamini G, Steiner MA, Clozel M.Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology(Berl).2021;238(10):2693-2708. doi:10.1007/s00213-021-05954-0
52. Roch C, Bergamini G, Steiner MA, Clozel M.Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology(Berl).2021;238(10):2693-2708. doi:10.1007/s00213-021-05954-0
53. Beuckmann CT, Ueno T, Nakagawa M, Suzuki M,Akasofu S. Preclinical in vivo characterization of lemborexant(E2006), a novel dual orexin receptor antagonist for sleep/wake regulation. Sleep.2019;42(6). doi:10.1093/sleep/zsz076
54. Muehlan C, Vaillant C, Zenklusen I, Kraehenbuehl S,Dingemanse J. Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders. Expert Opin Drug Metab Toxicol.2020;16(11):1063-1078.doi:10.1080/17425255.2020.1817380
55. Roch C, Bergamini G, Steiner MA, Clozel M.Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology(Berl).2021;238(10):2693-2708. doi:10.1007/s0021