{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:03:35Z","timestamp":1791925415330,"version":"4.3.4"},"reference-count":106,"publisher":"MedWorks Media","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Psychopharmacol Bull"],"abstract":"<jats:p>Purpose of Review\nInsomnia affects more than 10% of the population and causes significant discomfort and disability. Suvorexant is an orexin receptor antagonist that specifically targets the wake-sleep cycle. This review summarizes recent and seminal evidence in the biological and physiological evidence of insomnia, the mechanism of action of suvorexant in treating insomnia, and clinical evidence regarding its use.\nRecent Findings\nThere is no single clear diagnosis for insomnia, and thus prevalence is not entirely clear, but it is estimated to affect 10%\u201330% of the adult population. Comorbidities include obesity, diabetes, and various psychiatric conditions, and insomnia likely has a contributing role in these conditions. Insomnia, by definition, impacts sleep quality and also wakefulness, including academic success and work efficiency. Insomnia is likely related to genetic susceptibility and a triggering event, leading to hyper-arousal states and functional brain disturbances. This leads to hyperactivity of the hypothalamic-pituitary-adrenal axis, over-secretion of corticotropin-releasing factor, and aberrancy in neurotransmitter release. Though several pharmacological options exist for the treatment of insomnia, there is equivocal data regarding their efficacy or limits to their use due to side effects and contraindications. Suvorexant is a novel dual orexin receptor antagonist, which is shown to improve sleep by reducing arousals. Unlike classical therapeutics, suvorexant does not alter the sleep profile; it prolongs the time spent in each sleep state. Though it may cause some somnolence, it is milder than reported with other drugs.\nSummary\nMultiple clinical studies support the use of suvorexant in insomnia. In primary insomnia, suvorexant is effective (over placebo), as measured by polysomnography and reported by patients, in both attaining and maintaining sleep. Similar, albeit to a smaller degree, results were found in secondary insomnia. Suvorexant carries two significant advantages over existing therapies; it has a much better safety profile in approved doses, and it preserves natural sleep architecture, thus promoting more restful sleep and recovery. Unfortunately, data exists mostly for suvorexant versus placebo, and head-to-head trials with common hypnotics are needed to assess the true efficacy of suvorexant over the alternatives. And while tolerance is less likely to develop, close monitoring of post-marketing data is required to evaluate for long term adverse events and efficacy.<\/jats:p>","DOI":"10.64719\/pb.4429","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:39:16Z","timestamp":1761046756000},"page":"68-90","source":"Crossref","is-referenced-by-count":7,"title":["Suvorexant in the Treatment of Difficulty Falling and Staying Asleep (Insomnia)"],"prefix":"10.64719","volume":"52","author":[{"given":"Amnon A","family":"Berger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily R","family":"Sottosanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Winnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Keefe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elasaf","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Hasoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E","family":"Thase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D","family":"Kaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Viswanath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Urits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54175","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref1","unstructured":"Angel HE. Archives in Developing Countries: Iran as a Case Study n.d"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Ohayon MM, Reynolds CF. Epidemiological and clinical relevance of insomnia diagnosis algorithms according to the DSM-IV and the International Classification of Sleep Disorders (ICSD) Sleep Med. 2009;10(9):952\u2013960.","DOI":"10.1016\/j.sleep.2009.07.008"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"International Classification of Sleep Disorders Third Edition. Chest. 2014;146(5):1387\u20131394.","DOI":"10.1378\/chest.14-0970"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Olfson M, Wall M, Liu S-M, Morin CM, Blanco C. Insomnia and Impaired Quality of Life in the United States. J Clin Psychiatry. 2018;79(5):0\u20130.","DOI":"10.4088\/JCP.17m12020"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Morin CM, B\u00e9langer L, LeBlanc M et al. The natural history of insomnia a population-based 3-year longitudinal study. Arch Intern Med. 2009;169(5):447\u2013453.","DOI":"10.1001\/archinternmed.2008.610"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Cappuccio FP, D\u2019Elia L, Strazzullo P, Miller MA. Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2010;33(2):414\u2013420.","DOI":"10.2337\/dc09-1124"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Mildestvedt T, Herikstad VV, Undheim I, Bjorvatn B, Meland E. Factors associated with self-rated health in primary care. Scand J Prim Health Care. 2018;36(3):317\u2013322.","DOI":"10.1080\/02813432.2018.1499590"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Krystal AD, Prather AA, Liza H. The assessment and management of insomnia: an update n.d.:337\u2013352.","DOI":"10.1002\/wps.20674"},{"key":"ref9","unstructured":"Daley M, Morin CM, Leblanc M, Gr\u00e9goire J-P, Savard J. The Economic Burden of Insomnia: direct and Indirect Costs for Individuals with Insomnia Syndrome, Insomnia Symptoms, and Good Sleepers. Sleep. 2009;32(1):55\u201364."},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Norman JL, Anderson SL. Novel class of medications, orexin receptor antagonists, in the treatment of insomnia-critical appraisal of suvorexant. Nat Sci Sleep. 2016:239\u2013247.","DOI":"10.2147\/NSS.S76910"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Sheridan C. Insomniacs get new mechanism sleep drug Belsomra. Nat Biotechnol. 2014;32(10):968.","DOI":"10.1038\/nbt1014-968"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Roth T, Roehrs T, Pies R. Insomnia: pathophysiology and implications for treatment. Sleep Med Rev. 2007:71\u201379.","DOI":"10.1016\/j.smrv.2006.06.002"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Leger D, Guilleminault C, Dreyfus JP, Delahaye C, Paillard M. Prevalence of insomnia in a survey of 12,778 adults in France. J Sleep Res. 2000;9(1):35\u201342.","DOI":"10.1046\/j.1365-2869.2000.00178.x"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Grewal RG, Doghramji K. Epidemiology of Insomnia. Clinical Handbook of Insomnia. Springer International Publishing. 2017:13\u201325.","DOI":"10.1007\/978-3-319-41400-3_2"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Seow LSE, Verma S, Mok YM et al. Evaluating DSM-5 Insomnia Disorder and the Treatment of Sleep Problems in a Psychiatric Population. J Clin Sleep Med. 2018;14(02):237\u2013244.","DOI":"10.5664\/jcsm.6942"},{"key":"ref16","unstructured":"Desk Reference to the Diagnostic Criteria From DSM-5\u00ae\u2014American Psychiatric Association\u2014Google Books"},{"key":"ref17","unstructured":"The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines World Health Organization. n.d"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Chung KF, Yeung WF, Ho FYY, Yung KP, Yu YM, Kwok CW. Cross-cultural and comparative epidemiology of insomnia: the Diagnostic and Statistical Manual (DSM), International Classification of Diseases (ICD) and International Classification of Sleep Disorders (ICSD) Sleep Med. 2015;16(4):477\u2013482.","DOI":"10.1016\/j.sleep.2014.10.018"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Perlis ML, Vargas I, Ellis JG et al. The Natural History of Insomnia: the incidence of acute insomnia and subsequent progression to chronic insomnia or recovery in good sleeper subjects. Sleep. 2020;43(6):zsz299.","DOI":"10.1093\/sleep\/zsz299"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Morin CM, Jarrin DC, Ivers H, M\u00e9rette C, LeBlanc M, Savard J. Incidence, Persistence, and Remission Rates of Insomnia Over 5 Years. JAMA Netw Open. 2020;3(11):e2018782.","DOI":"10.1001\/jamanetworkopen.2020.18782"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Morin CM, Drake CL, Harvey AG et al. Insomnia disorder. Nat Rev Dis. 2015:1. Prim.","DOI":"10.1038\/nrdp.2015.26"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"O\u2019Brien EM, Chelminski I, Young D, Dalrymple K, Hrabosky J, Zimmerman M. Severe insomnia is associated with more severe presentation and greater functional deficits in depression. J Psychiatr Res. 2011;45(8):1101\u20131105.","DOI":"10.1016\/j.jpsychires.2011.01.010"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Biddle DJ, Kelly PJ, Hermens DF, Glozier N. The association of insomnia with future mental illness: is it just residual symptoms. Sleep Heal. 2018;4(4):352\u2013359.","DOI":"10.1016\/j.sleh.2018.05.008"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Zhang Y, Lin Y, Zhang J et al. Association between insomnia and type 2 diabetes mellitus in Han Chinese individuals in Shandong Province, China. Sleep Breath. 2019;23(1):349\u2013354.","DOI":"10.1007\/s11325-018-1687-6"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Sundbom F, Malinovschi A, Lindberg E, Almqvist C, Janson C. Insomnia symptoms and asthma control\u2014Interrelations and importance of comorbidities. Clin Exp Allergy. 2020;50(2):170\u2013177.","DOI":"10.1111\/cea.13517"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Cai GH, Theorell-Hagl\u00f6w J, Janson C et al. Insomnia symptoms and sleep duration and their combined effects in relation to associations with obesity and central obesity. Sleep Med. 2018;46:81\u201387.","DOI":"10.1016\/j.sleep.2018.03.009"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Javaheri S, Redline S. Insomnia and Risk of Cardiovascular Disease. Chest. 2017:435\u2013444.","DOI":"10.1016\/j.chest.2017.01.026"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Sofi F, Cesari F, Casini A, Macchi C, Abbate R, Gensini GF. Insomnia and risk of cardiovascular disease: a meta-analysis. Eur J Prev Cardiol. 2014;21(1):57\u201364.","DOI":"10.1177\/2047487312460020"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"McCall WV, Black CG. The link between suicide and insomnia: theoretical mechanisms. Curr Psychiatry Rep. 2013;15(9):389.","DOI":"10.1007\/s11920-013-0389-9"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Kim J, Cho SJ, Kim WJ, Yang KI, Yun CH, Chu MK. Insomnia in probable migraine: a population-based study. J Headache Pain. 2016;17(1):92.","DOI":"10.1186\/s10194-016-0681-2"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Levenson JC, Kay DB, Buysse DJ. The pathophysiology of insomnia. Chest. 2015;147(4):1179\u20131192.","DOI":"10.1378\/chest.14-1617"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Riemann D, Spiegelhalder K, Feige B et al. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev. 2010:19\u201331.","DOI":"10.1016\/j.smrv.2009.04.002"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"O\u2019Byrne JN, Berman Rosa M, Gouin JP, Dang-Vu TT. Neuroimaging findings in primary insomnia. Pathol Biol. 2014:262\u2013269.","DOI":"10.1016\/j.patbio.2014.05.013"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Bagherzadeh-Azbari S, Khazaie H, Zarei M et al. Neuroimaging insights into the link between depression and Insomnia: a systematic review. J Affect Disord. 2019:133\u2013143.","DOI":"10.1016\/j.jad.2019.07.089"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Liu X, Zheng J, Liu BX, Dai XJ. Altered connection properties of important network hubs may be neural risk factors for individuals with primary insomnia. Sci Rep. 2018;8(1):1\u201313.","DOI":"10.1038\/s41598-018-23699-3"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Dai XJ, Nie X, Liu X et al. Gender differences in regional brain activity in patients with chronic primary insomnia: evidence from a resting-state fMRI study. J Clin Sleep Med. 2016;12(3):363\u2013374.","DOI":"10.5664\/jcsm.5586"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"LeBlanc M, M\u00e9rette C, Savard J, Ivers H, Baillargeon L, Morin CM. Incidence and risk factors of insomnia in a population-based sample. Sleep. 2009;32(8):1027\u20131037.","DOI":"10.1093\/sleep\/32.8.1027"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Valli\u00e8res A, Azaiez A, Moreau V, LeBlanc M, Morin CM. Insomnia in shift work. Sleep Med. 2014;15(12):1440\u20131448.","DOI":"10.1016\/j.sleep.2014.06.021"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Ara T, Rahman MM, Hossain MA, Ahmed A. Identifying the Associated Risk Factors of Sleep Disturbance During the COVID-19 Lockdown in Bangladesh: a web-based survey. Front Psychiatry. 2020;11:580268.","DOI":"10.3389\/fpsyt.2020.580268"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Patel D, Steinberg J, Patel P. Insomnia in the Elderly: a review. J Clin Sleep Med. 2018;14(06):1017\u20131024.","DOI":"10.5664\/jcsm.7172"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Morgan K. Daytime activity and risk factors for late-life insomnia. J Sleep Res. 2003;12(3):231\u2013238.","DOI":"10.1046\/j.1365-2869.2003.00355.x"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Zhang B, Wing YK. Sex differences in insomnia: a meta-analysis. Sleep. 2006;29(1):85\u201393.","DOI":"10.1093\/sleep\/29.1.85"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Voderholzer U, Al-Shajlawi A, Weske G, Feige B, Riemann D. Are there gender differences in objective and subjective sleep measures? A study of insomniacs and healthy controls. Depress Anxiety. 2003;17(3):162\u2013172.","DOI":"10.1002\/da.10101"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Suh S, Cho N, Zhang J. Sex Differences in Insomnia: from Epidemiology and Etiology to Intervention. Curr Psychiatry Rep. 2018:1\u201312.","DOI":"10.1007\/s11920-018-0940-9"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Riemann D, Baglioni C, Bassetti C et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675\u2013700.","DOI":"10.1111\/jsr.12594"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"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"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Solomon CG, Winkelman JW. Clinical Practice Insomnia Disorder. N Engl J Med. 2015;373:1437\u20131481.","DOI":"10.1056\/NEJMcp1412740"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Wu JQ, Appleman ER, Salazar RD, Ong JC. Cognitive behavioral therapy for insomnia comorbid with psychiatric and medical conditions a meta-analysis. JAMA Intern Med. 2015;175(9):1461\u20131472.","DOI":"10.1001\/jamainternmed.2015.3006"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Brasure M, Fuchs E, MacDonald R et al. Psychological and Behavioral Interventions for Managing Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians. Ann Intern Med. 2016;165(2):113.","DOI":"10.7326\/M15-1782"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Hall-porter JM, Curry DT, Walsh JK. Pharmacologic Treatment of Primary Insomnia. Clin Sleep Med. 2020;5(4):609\u2013625.","DOI":"10.1016\/j.jsmc.2010.08.006"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Roehrs T, Roth T. Insomnia Pharmacotherapy. Neurotherapeutics. 2012:728\u2013738.","DOI":"10.1007\/s13311-012-0148-3"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Morin C, Benca R. Chronic insomnia. Lancet. 2012;379(9821):1129\u20131141.","DOI":"10.1016\/S0140-6736(11)60750-2"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"Walsh JK, Krystal AD, Amato DA et al. Nightly Treatment of Primary Insomnia With Eszopiclone for Six Months: effect on sleep, quality of life, and work limitations. Sleep. 2007;30(8):959\u2013968.","DOI":"10.1093\/sleep\/30.8.959"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Study M, Krystal AD, Erman M et al. Long-Term Efficacy and Safety of Zolpidem Extended-Release 12.5 mg, Administered 3 to 7 Nights Per Week for 24 Weeks, in Patients With Chronic Primary Insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Sleep. 2008;31(1):79\u201390.","DOI":"10.1093\/sleep\/31.1.79"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Ancoli-israel S, Richardson GS, Mangano RM, Jenkins L, Hall P, Jones WS. Long-term use of sedative hypnotics in older patients with insomnia. 2005;6:107\u2013113.","DOI":"10.1016\/j.sleep.2004.10.015"},{"key":"ref56","doi-asserted-by":"crossref","unstructured":"Morin CM, Edinger JD, Beaulieu-bonneau S et al. Effectiveness of Sequential Psychological and Medication Therapies for Insomnia Disorder A Randomized Clinical Trial. 2020:1\u20139.","DOI":"10.1001\/jamapsychiatry.2020.1767"},{"key":"ref57","unstructured":"Buysse DJ. CLINICIAN \u2019 S CORNER Insomnia MS J: HER VIEW. 2020"},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"Roth T, Seiden D, Sainati S, Wang-weigand S, Zhang J, Zee P. Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia*. 2006;7:312\u2013318.","DOI":"10.1016\/j.sleep.2006.01.003"},{"key":"ref59","doi-asserted-by":"crossref","unstructured":"Roehrs T, Roth T. Insomnia Pharmacotherapy. 2012 September;:728\u2013738.","DOI":"10.1007\/s13311-012-0148-3"},{"key":"ref60","unstructured":"Krystal AD, Lankford A, Durrence HH et al. Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia n.d"},{"key":"ref61","doi-asserted-by":"crossref","unstructured":"Schweitzer PK, Muehlbach MJ, Welsh JK. Sleepiness and performance during three-day administration of cetirizine or diphenhydramine. J Allergy Clin Immunol. 1994;94(4):716\u2013724.","DOI":"10.1016\/0091-6749(94)90179-1"},{"key":"ref62","doi-asserted-by":"crossref","unstructured":"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. J Clin Sleep Med. 2017;13(2):307\u2013349.","DOI":"10.5664\/jcsm.6470"},{"key":"ref63","doi-asserted-by":"crossref","unstructured":"Parish J, Lee-Iannotti J. Suvorexant: a promising, novel treatment for insomnia. Neuropsychiatr Dis Treat. 2016;12:491.","DOI":"10.2147\/NDT.S31495"},{"key":"ref64","doi-asserted-by":"crossref","unstructured":"Cox CD, Breslin MJ, Whitman DB et al. Discovery of the dual orexin receptor antagonist [(7 R)-4-(5-chloro-1,3- benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2 H -1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomnia. J Med Chem. 2010;53(14):5320\u20135332.","DOI":"10.1021\/jm100541c"},{"key":"ref65","unstructured":"Bennett T, Bray D, Neville MW. Suvorexant, a dual orexin receptor antagonist for the management of insomnia. 2014:264\u2013266. P T."},{"key":"ref66","doi-asserted-by":"crossref","unstructured":"Riemann D, Baglioni C, Bassetti C et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675\u2013700.","DOI":"10.1111\/jsr.12594"},{"key":"ref67","doi-asserted-by":"crossref","unstructured":"Jacobson LH, Callander GE, Hoyer D. Suvorexant for the treatment of insomnia. Expert Rev Clin Pharmacol. 2014:711\u2013730.","DOI":"10.1586\/17512433.2014.966813"},{"key":"ref68","doi-asserted-by":"crossref","unstructured":"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):e12782.","DOI":"10.1111\/jsr.12782"},{"key":"ref69","doi-asserted-by":"crossref","unstructured":"Brisbare-Roch C, Dingemanse J, Koberstein R et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med. 2007;13(2):150\u2013155.","DOI":"10.1038\/nm1544"},{"key":"ref70","doi-asserted-by":"crossref","unstructured":"Baumann CR, Bassetti CL. Hypocretins (orexins) and sleep-wake disorders. Lancet Neurol. 2005:673\u2013682.","DOI":"10.1016\/S1474-4422(05)70196-4"},{"key":"ref71","doi-asserted-by":"crossref","unstructured":"Ohno K, Sakurai T. Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrinol. 2008:70\u201387.","DOI":"10.1016\/j.yfrne.2007.08.001"},{"key":"ref72","doi-asserted-by":"crossref","unstructured":"Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007:171\u2013181.","DOI":"10.1038\/nrn2092"},{"key":"ref73","doi-asserted-by":"crossref","unstructured":"Winrow CJ, Gotter AL, Cox CD et al. Promotion of sleep by Suvorexant\u2014A novel dual orexin receptor antagonist. J Neurogenet. 2011;25(1\u20132):52\u201361.","DOI":"10.3109\/01677063.2011.566953"},{"key":"ref74","doi-asserted-by":"crossref","unstructured":"Keks NA, Hope J, Keogh S. Suvorexant: scientifically interesting, utility uncertain. Australas Psychiatry. 2017;25(6):622\u2013624.","DOI":"10.1177\/1039856217734677"},{"key":"ref75","doi-asserted-by":"crossref","unstructured":"Yee KL, McCrea J, Panebianco D et al. Safety, Tolerability, and Pharmacokinetics of Suvorexant: a randomized rising-dose trial in healthy men. Clin Drug Investig. 2018;38(7):631\u2013638.","DOI":"10.1007\/s40261-018-0650-4"},{"key":"ref76","unstructured":"Station W. Suvorexant Advisory Committee Meeting Briefing Document Suvorexant Tablets Insomnia Indication. 2013:1\u2013148. NDA 204569. Peripheral & Central Nervous System Drugs Advisory Committee Meeting Merck Sharp & Dohme Corporation ADVISORY COMMITTEE BRIEFING DOCUMENT AVAILABLE."},{"key":"ref77","doi-asserted-by":"crossref","unstructured":"Herring WJ, Connor KM, Snyder E et al. Suvorexant in patients with insomnia: pooled analyses of three-month data from phase-3 randomized controlled clinical trials. J Clin Sleep Med. 2016;12(9):1215\u20131225.","DOI":"10.5664\/jcsm.6116"},{"key":"ref78","doi-asserted-by":"crossref","unstructured":"Herring WJ, Connor KM, Ivgy-May N et al. Suvorexant in Patients with Insomnia: results from two 3-month randomized controlled clinical trials. Biol Psychiatry. 2016;79(2):136\u2013148.","DOI":"10.1016\/j.biopsych.2014.10.003"},{"key":"ref79","doi-asserted-by":"crossref","unstructured":"Michelson D, Snyder E, Paradis E et al. 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;13(5):461\u2013471.","DOI":"10.1016\/S1474-4422(14)70053-5"},{"key":"ref80","doi-asserted-by":"crossref","unstructured":"Sutton E. Profile of suvorexant in the management of insomnia. Drug Des Devel Ther. 2015;9:6035.","DOI":"10.2147\/DDDT.S73224"},{"key":"ref81","doi-asserted-by":"crossref","unstructured":"Herring WJ, Snyder E, Budd K et al. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012;79(23):2265\u20132274.","DOI":"10.1212\/WNL.0b013e31827688ee"},{"key":"ref82","doi-asserted-by":"crossref","unstructured":"Kawabe K, Horiuchi F, Ochi M, Nishimoto K, Ueno S, Oka Y. Suvorexant for the Treatment of Insomnia in Adolescents. J Child Adolesc Psychopharmacol. 2017;27(9):792\u2013795.","DOI":"10.1089\/cap.2016.0206"},{"key":"ref83","doi-asserted-by":"crossref","unstructured":"Herring WJ, Ceesay P, Snyder E et al. Polysomnographic assessment of suvorexant in patients with probable Alzheimer\u2019s disease dementia and insomnia: a randomized trial. Alzheimer\u2019s Dement. 2020;16(3):541\u2013551.","DOI":"10.1002\/alz.12035"},{"key":"ref84","doi-asserted-by":"crossref","unstructured":"Zeitzer JM, Joyce DS, McBean A, Quevedo YL, Hernandez B, Holty J-E. Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers. JAMA Netw Open. 2020;3(6):e206614.","DOI":"10.1001\/jamanetworkopen.2020.6614"},{"key":"ref85","doi-asserted-by":"crossref","unstructured":"Michelson D, Snyder E, Paradis E et al. 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;13(5):461\u2013471.","DOI":"10.1016\/S1474-4422(14)70053-5"},{"key":"ref86","doi-asserted-by":"crossref","unstructured":"Hatano M, Kamei H, Inagaki R et al. Assessment of switching to suvorexant versus the use of add-on suvorexant in combination with benzodiazepine receptor agonists in insomnia patients: a retrospective study. Clin Psychopharmacol Neurosci. 2018;16(2):184\u2013189.","DOI":"10.9758\/cpn.2018.16.2.184"},{"key":"ref87","doi-asserted-by":"crossref","unstructured":"Roehrs T, Withrow D, Koshorek G, Verkler J, Bazan L, Roth T. Sleep and pain in humans with fibromyalgia and comorbid insomnia: double-blind, crossover study of suvorexant 20 mg versus placebo. J Clin Sleep Med. 2020;16(3):415\u2013421.","DOI":"10.5664\/jcsm.8220"},{"key":"ref88","doi-asserted-by":"crossref","unstructured":"Yoshikawa F, Shigiyama F, Ando Y et al. Chronotherapeutic efficacy of suvorexant on sleep quality and metabolic parameters in patients with type 2 diabetes and insomnia. Diabetes Res Clin Pract. 2020:169.","DOI":"10.1016\/j.diabres.2020.108412"},{"key":"ref89","doi-asserted-by":"crossref","unstructured":"Azimaraghi O, Hammer M, Santer P et al. Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. BMJ Open. 2020;10(7):e038474.","DOI":"10.1136\/bmjopen-2020-038474"},{"key":"ref90","doi-asserted-by":"crossref","unstructured":"Campbell EJ, Norman A, Bonomo Y, Lawrence AJ. Suvorexant to treat alcohol use disorder and comorbid insomnia: plan for a phase II trial. Brain Res. 2020:146597.","DOI":"10.1016\/j.brainres.2019.146597"},{"key":"ref91","doi-asserted-by":"crossref","unstructured":"Rhyne DN, Anderson SL. Suvorexant in insomnia: efficacy, safety and place in therapy. Ther Adv Drug Saf. 2015;6(5):189\u2013195.","DOI":"10.1177\/2042098615595359"},{"key":"ref92","doi-asserted-by":"crossref","unstructured":"Anderson S, Norman J. Novel class of medications, orexin receptor antagonists, in the treatment of insomnia critical appraisal of suvorexant. Nat Sci Sleep. 2016;8:239\u2013247.","DOI":"10.2147\/NSS.S76910"},{"key":"ref93","doi-asserted-by":"crossref","unstructured":"Herring WJ, Connor KM, Snyder E et al. Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data. Psychopharmacology (Berl). 2017;234(11):1703\u20131711.","DOI":"10.1007\/s00213-017-4573-1"},{"key":"ref94","doi-asserted-by":"crossref","unstructured":"Snyder E, Ma J, Svetnik V et al. Effects of suvorexant on sleep architecture and power spectral profile in patients with insomnia: analysis of pooled phase 3 data. Sleep Med. 2016;19:93\u2013100.","DOI":"10.1016\/j.sleep.2015.10.007"},{"key":"ref95","doi-asserted-by":"crossref","unstructured":"Herring WJ, Connor KM, Snyder E et al. Suvorexant in Elderly Patients with Insomnia: pooled analyses of data from phase iii randomized controlled clinical trials. Am J Geriatr Psychiatry. 2017;25(7):791\u2013802.","DOI":"10.1016\/j.jagp.2017.03.004"},{"key":"ref96","doi-asserted-by":"crossref","unstructured":"Svetnik V, Snyder ES, Tao P et al. Insight into reduction of wakefulness by suvorexant in patients with insomnia: analysis of wake bouts. Sleep. 2018;41(1)","DOI":"10.1093\/sleep\/zsx178"},{"key":"ref97","doi-asserted-by":"crossref","unstructured":"Herring WJ, Connor KM, Snyder E et al. Effects of suvorexant on the Insomnia Severity Index in patients with insomnia: analysis of pooled phase 3 data. Sleep Med. 2019;56:219\u2013223.","DOI":"10.1016\/j.sleep.2018.09.010"},{"key":"ref98","doi-asserted-by":"crossref","unstructured":"Sano H, Asai Y, Miyazaki M, Iwakura M, Maeda Y, Hara M. Safety profile and clinical course of patients with insomnia administered suvorexant by initial treatment status in a post-marketing survey. Expert Opin Drug Saf. 2019;18(11):1109\u20131118.","DOI":"10.1080\/14740338.2019.1657091"},{"key":"ref99","doi-asserted-by":"crossref","unstructured":"Kishi T, Nomura I, Matsuda Y et al. Lemborexant vs suvorexant for insomnia: a systematic review and network meta-analysis. J Psychiatr Res. 2020;128:68\u201374.","DOI":"10.1016\/j.jpsychires.2020.05.025"},{"key":"ref100","doi-asserted-by":"crossref","unstructured":"Rosenberg R, Murphy P, Zammit G et al. Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: a phase 3 randomized clinical trial. JAMA Netw Open. 2019;2(12):e1918254.","DOI":"10.1001\/jamanetworkopen.2019.18254"},{"key":"ref101","doi-asserted-by":"crossref","unstructured":"Sun H, Kennedy WP, Wilbraham D et al. Effects of Suvorexant, an Orexin Receptor Antagonist, on Sleep Parameters as Measured by Polysomnography in Healthy Men. Sleep. 2013;36(2):259\u2013267.","DOI":"10.5665\/sleep.2386"},{"key":"ref102","unstructured":"HIGHLIGHTS OF PRESCRIBING INFORMATION. n.d"},{"key":"ref103","unstructured":"Suvorexant: Drug information - UpToDate. [November 19, 2020]; Available at: https:\/\/www.uptodate.com\/contents\/suvorexant-drug-information?search=suvorexant&source=panel_search_result&selectedTitle=1~10&usage_type=panel&kp_tab=drug_general&display_rank=1#F25576291. Accessed."},{"key":"ref104","doi-asserted-by":"crossref","unstructured":"Petrous J, Furmaga K. Adverse reaction with suvorexant for insomnia: acute worsening of depression with emergence of suicidal thoughts. BMJ Case Rep. 2017;2017 bcr-2017-222037.","DOI":"10.1136\/bcr-2017-222037"},{"key":"ref105","doi-asserted-by":"crossref","unstructured":"Sun H, Palcza J, Card D et al. Effects of Suvorexant, an Orexin Receptor Antagonist, on Respiration during Sleep In Patients with Obstructive Sleep Apnea. J Clin Sleep Med. 2016;12(01):9\u201317.","DOI":"10.5664\/jcsm.5382"},{"key":"ref106","doi-asserted-by":"crossref","unstructured":"Takano M, Okada T, Kobayashi T, Suda S. Syndrome of inappropriate antidiuretic hormone secretion induced by suvorexant: a case report. J Clin Sleep Med. 2020","DOI":"10.5664\/jcsm.8970"}],"container-title":["Psychopharmacology Bulletin"],"original-title":[],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:30:23Z","timestamp":1791315023000},"score":1,"resource":{"primary":{"URL":"https:\/\/medworksmedia.com\/pb-article\/suvorexant-in-the-treatment-of-difficulty-falling-and-staying-asleep-insomnia\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":106,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,8,12]]}},"URL":"https:\/\/doi.org\/10.64719\/pb.4429","relation":{},"ISSN":["2472-2448"],"issn-type":[{"value":"2472-2448","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]}}}