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V.E. Medvedev

Patrice Lumumba Peoples Friendship University of Russia

N.V. Titova

Federal Center of Brain and Neurotechnologies;
Pirogov Russian National Research Medical University

I.V. Milyukhina

N. Bechtereva Institute of the Human Brain

F.Sh. Shagiakhmetov

National Scientific Center for Narcology — Branch «Serbsky National Medical Research Center of Psychiatry and Narcology»

R.R. Borukaev

LLC «Angelini Pharma Rus»

I.V. Kolyvanova

LLC «Angelini Pharma Rus»

Slow-wave sleep and the possibilities of modern insomnia therapy

Authors:

V.E. Medvedev, N.V. Titova, I.V. Milyukhina, F.Sh. Shagiakhmetov, R.R. Borukaev, I.V. Kolyvanova

More about the authors

Read: 3944 times


To cite this article:

Medvedev VE, Titova NV, Milyukhina IV, Shagiakhmetov FSh, Borukaev RR, Kolyvanova IV. Slow-wave sleep and the possibilities of modern insomnia therapy. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(8):49‑55. (In Russ.)
https://doi.org/10.17116/jnevro202312308149

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References:

  1. Everitt H, Baldwin DS, Stuart B, et al. Antidepressants for insomnia in adults. Cochrane Database Syst Rev. 2018;5(5):CD010753. https://doi.org/10.1002/14651858.CD010753.pub2
  2. Kaur H, Spurling BC, Bollu PC. Chronic Insomnia. [Updated 2023 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.  https://www.ncbi.nlm.nih.gov/books/NBK526136/
  3. Buysse DJ. Insomnia. JAMA. 2013;309(7):706-716.  https://doi.org/10.1001/jama.2013.193
  4. Vande-Griend JP, Anderson SL. Histamine-1 receptor antagonism for treatment of insomnia. J Am Pharm Assoc (2003). 2012;52(6):e210-9.  https://doi.org/10.1331/JAPhA.2012.12051
  5. Pelayo R, Bertisch SM, Morin CM, et al. Should Trazodone Be First-Line Therapy for Insomnia? A Clinical Suitability Appraisal. Journal of Clinical Medicine. 2023;12(8):2933. https://doi.org/10.3390/jcm12082933
  6. Fagiolini A, Comandini A, Catena Dell’Osso M, Kasper S. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012;26(12):1033-1049. https://doi.org/10.1007/s40263-012-0010-5
  7. Schwartz TL, Goradia V. Managing insomnia: an overview of insomnia and pharmacologic treatment strategies in use and on the horizon. Drugs Context. 2013;2013:212257. https://doi.org/10.7573/dic.212257
  8. Jaffer KY, Chang T, Vanle B, et al. Trazodone for Insomnia: A Systematic Review. Innov Clin Neurosci. 2017;14(7-8):24-34. 
  9. Carskadon M, Dement W. Normal human sleep: An overview. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia: Elsevier Saunders; 2005.
  10. Walsh JK. Enhancement of slow wave sleep: implications for insomnia. J Clin Sleep Med. 2009;5(2 suppl):27-32. 
  11. Tononi G, Cirelli C. Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull. 2003;62:143-150. 
  12. Walker M. The role of slow wave sleep in memory processing. J Clin Sleep Med. 2009;5(suppl):20-26. 
  13. Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373-377.  https://doi.org/10.1126/science.1241224
  14. Hablitz LM, Vinitsky HS, Sun Q, et al. Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. Sci Adv. 2019;5(2):eaav5447. Published 2019 Feb 27.  https://doi.org/10.1126/sciadv.aav5447
  15. Reddy OC, van der Werf YD. The Sleeping Brain: Harnessing the Power of the Glymphatic System through Lifestyle Choices. Brain Sci. 2020;10(11):868. Published 2020 Nov 17.  https://doi.org/10.3390/brainsci10110868
  16. Bacyinski A, Xu M, Wang W, Hu J. The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy. Front Neuroanat. 2017;11:101. Published 2017 Nov 7.  https://doi.org/10.3389/fnana.2017.00101
  17. Colten HR, Altevogt BM, eds. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington (DC): National Academies Press (US); 2006. 2, Sleep Physiology. Institute of Medicine (US) Committee on Sleep Medicine and Research. https://www.ncbi.nlm.nih.gov/books/NBK19956/
  18. de Mendonça FMR, de Mendonça GPRR, Souza LC, et al. Benzodiazepines and Sleep Architecture: A Systematic Review. CNS Neurol Disord Drug Targets. 2023;22(2):172-179.  https://doi.org/10.2174/1871527320666210618103344
  19. Atkin T, Comai S, Gobbi G. Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery. Pharmacol Rev. 2018;70(2):197-245.  https://doi.org/10.1124/pr.117.014381
  20. Shagiakhmetov FSh. Atypical antipsychotics: more similarities or differences? Theoretical background (part 1). STPN. 2014;1:14-22. (In Russ.). https://cyberleninka.ru/article/n/atipichnye-antipsihotiki-bolshe-shodstv-ili-razlichiy-teoreticheskie-predposylki-chast-1
  21. Shagiakhmetov FSh. Atypical antipsychotics: more similarities or differences? Theoretical Background (part 2). STPN. 2014;2:4-9. (In Russ.). https://cyberleninka.ru/article/n/atipichnye-antipsihotiki-bolshe-shodstv-ili-razlichiy-teoreticheskie-predposylki-chast-2
  22. Hecht Orzack M, Cole JO, Friedman L, Bird M, McEachern J. Weight changes in antidepressants: a comparison of amitriptyline and trazodone. Neuropsychobiology. 1986;15(suppl 1):28-30.  https://doi.org/10.1159/000118237
  23. Bjorvatn B, Ursin R. Changes in sleep and wakefulness following 5-HT1A ligands given systemically and locally in different brain regions. Rev Neurosci. 1998;9(4):265-273.  https://doi.org/10.1515/revneuro.1998.9.4.265
  24. Petrova NN, Shagiakhmetov FSh, Borukaev RR. Trazodone: facets of clinical efficacy. Psychiatry and Psychopharmacotherapy. 2021;23(3):40-46. (In Russ.).
  25. Kleinlogel H. Effects of the selective alpha 1-adrenoceptor blocker prazosin on EEG sleep and waking stages in the rat. Neuropsychobiology. 1989;21(2):100-103.  https://doi.org/10.1159/000118560
  26. Fulda S, Kloiber S, Dose T, et al. Mirtazapine provokes periodic leg movements during sleep in young healthy men. Sleep. 2013;36(5):661-669.  https://doi.org/10.5665/sleep.2622
  27. Haldar P, Haldar P. Mirtazapine Aggravates Restless Leg Syndrome:A Case Report. Indian J Psychiatry. 2022;64(suppl 3):586-587.  https://doi.org/10.4103/0019-5545.341707
  28. Makiguchi A, Nishida M. Mirtazapine-Induced Restless Legs Syndrome Treated With Pramipexole. American Psychiatric Association Publishing. Published Online: 26 Feb 2015. https://doi.org/10.1176/appi.neuropsych.13120357
  29. Monti JM, Monti D. The involvement of dopamine in the modulation of sleep and waking. Sleep Med Rev. 2007;11:113-133.  https://doi.org/10.1016/j.smrv.2006.08.003
  30. Qu WM, Xu XH, Yan MM, et al. Essential role of dopamine D2 receptor in the maintenance of wakefulness, but not in homeostatic regulation of sleep, in mice. J Neurosci. 2019;30:4382-4389. https://doi.org/10.1523/JNEUROSCI.4936-09.2010
  31. Gedge L, Lazowski L, Murray D, et al. Effects of quetiapine on sleep architecture in patients with unipolar or bipolar depression. Neuropsychiatr Dis Treat. 2010;6:501-508.  https://doi.org/10.2147/ndt.s12433
  32. Sharpley AL, Vassallo CM, Cowen PJ. Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT(2C) receptors in vivo. Biol Psychiatry. 2000;47(5):468-470.  https://doi.org/10.1016/s0006-3223(99)00273-5
  33. Cohrs S, Meier A, Neumann AC. et al. Improved sleep continuity and increased slow wave sleep and REM latency during ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy male subjects. J Clin Psychiatry. 2005;66(8):989-996.  https://doi.org/10.4088/jcp.v66n0805
  34. Kuehn BM. FDA Warns Antipsychotic Drugs May Be Risky for Elderly. JAMA. 2005;293(20):2462. https://doi.org/10.1001/jama.293.20.2462
  35. Yan J. FDA Extends Black-Box Warning to All Antipsychotics. American Psychiatric Association Publishing/CLINICAL & RESEARCH NEWS Published Online: 18 Jul 2008. https://doi.org/10.1176/pn.43.14.0001
  36. Knol W, van Marum RJ, Jansen PA, et al. Antipsychotic drug use and risk of pneumonia in elderly people. J Am Geriatr Soc. 2008;56:661-666. 
  37. Pratt N, Roughead EE, Ramsay E, et al. Risk of hospitalization for hip fracture and pneumonia associated with antipsychotic prescribing in the elderly: a self-controlled case-series analysis in an Australian health care claims database. Drug Saf. 2011;34:567-575. 
  38. Trifiro G, Spina E, Gambassi G. Use of antipsychotics in elderly patients with dementia: do atypical conventional agents have a similar safety profile? Pharmacol Res. 2009;59:1-12. 
  39. Herzig SJ, LaSalvia MT, Naidus E, et al. Antipsychotics and the Risk of Aspiration Pneumonia in Individuals Hospitalized for Nonpsychiatric Conditions: A Cohort Study. J Am Geriatr Soc. 2017;65(12):2580-2586. https://doi.org/10.1111/jgs.15066
  40. Ostroumova OD, Goloborodova IV, Isaev RI, Pereverzev AP. Antipsychotics: features of undesirable adverse reactions in elderly and senile patients. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2019;119(2):105-117. (In Russ.). https://doi.org/10.17116/jnevro2019119021105
  41. Kheirbek RE, Fokar A, Little JT, et al. Association Between Antipsychotics and All-Cause Mortality Among Community-Dwelling Older Adults. J Gerontol A Biol Sci Med Sci. 2019;74(12):1916-1921. https://doi.org/10.1093/gerona/glz045
  42. Paus S, Brecht HM, Köster J, et al. Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson’s disease. Mov Disord. 2003;18(6):659-667.  https://doi.org/10.1002/mds.10417
  43. Monti JM, Jantos H. The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking. Prog Brain Res. 2008;172:625-46.  https://doi.org/10.1016/S0079-6123(08)00929-1
  44. Lagos P, Scorza C, Monti JM, et al. Effects of the D3 preferring dopamine agonist pramipexole on sleep and waking, locomotor activity and striatal dopamine release in rats. Eur Neuropsychopharmacol. 1998;8(2):113-120.  https://doi.org/10.1016/s0924-977x(97)00054-0
  45. Nodel’ MR. Effects of the dopamine agonist mirapex (pramipexole) therapy on sleep disorders in Parkinson’s disease. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2010;110(3):42-47. (In Russ.).
  46. Inoue Y, Hirata K, Kuroda K, et al. Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized, double-blind, placebo-controlled study. Sleep Med. 2010;11(1):11-16.  https://doi.org/10.1016/j.sleep.2009.03.009
  47. Jama L, Hirvonen K, Partinen M, et al. A dose-ranging study of pramipexole for the symptomatic treatment of restless legs syndrome: polysomnographic evaluation of periodic leg movements and sleep disturbance. Sleep Med. 2009;10(6):630-636.  https://doi.org/10.1016/j.sleep.2008.05.014
  48. Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG. Current Treatment Options for REM Sleep Behaviour Disorder. J Pers Med. 2021;11(11):1204. https://doi.org/10.3390/jpm11111204
  49. Tundo A, Betro’ S, de Filippis R, et al. Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis. Life. 2023;13(4):1043. https://doi.org/10.3390/life13041043
  50. Tundo A, Betro’ S, Iommi M, de Filippis R. Efficacy and safety of 24-week pramipexole augmentation in patients with treatment resistant depression. A retrospective cohort study. Prog Neuropsychopharmacol Biol Psychiatry. 2022;112:110425. https://doi.org/10.1016/j.pnpbp.2021.110425
  51. Tundo A, de Filippis R, De Crescenzo F. Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta-analysis. Acta Psychiatrica Scandinavica. 2019;140(2):116-125.  https://doi.org/10.1111/acps.13055
  52. Bazil CW, Dave J, Cole J, Stalvey J, Drake E. Pregabalin increases slow-wave sleep and may improve attention in patients with partial epilepsy and insomnia. Epilepsy Behav. 2012;23(4):422-425.  https://doi.org/10.1016/j.yebeh.2012.02.005
  53. Lo HS, Yang CM, Lo HG, et al. Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol. 2010;33(2):84-90.  https://doi.org/10.1097/WNF.0b013e3181cda242
  54. Foldvary-Schaefer N, De Leon Sanchez I, Karafa M, et al. Gabapentin increases slow-wave sleep in normal adults. Epilepsia. 2002;43(12):1493-1497. https://doi.org/10.1046/j.1528-1157.2002.21002.x
  55. Hindmarch I, Dawson J, and Stanley N. A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep. 2005;28(2):187-193.  https://doi.org/10.1093/sleep/28.2.187
  56. Garcia-Borreguero D, Patrick J, DuBrava S, et al. Pregabalin versus pramipexole: effects on sleep disturbance in restless legs syndrome. Sleep. 2014;37(4):635-643.  https://doi.org/10.5665/sleep.3558
  57. Kim ES, Deeks ED. Gabapentin Enacarbil: A Review in Restless Legs Syndrome. Drugs. 2016;76(8):879-887.  https://doi.org/10.1007/s40265-016-0584-1
  58. Weresch J, Kirkwood J, Korownyk CS. Gabapentin for alcohol use disorder. Can Fam Physician. 2021;67(4):269.  https://doi.org/10.46747/cfp.6704269
  59. Mason BJ, Quello S, Goodell V, et al. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014;174(1):70-77.  https://doi.org/10.1001/jamainternmed.2013.11950
  60. Karam-Hage M, Brower KJ. Gabapentin treatment for insomnia associated with alcohol dependence. Am J Psychiatry. 2000;157(1):151. 
  61. Brower KJ, Myra Kim H, Strobbe S, et al. A randomized double-blind pilot trial of gabapentin versus placebo to treat alcohol dependence and comorbid insomnia. Alcohol Clin Exp Res. 2008;32(8):1429-1438. https://doi.org/10.1111/j.1530-0277.2008.00706.x
  62. Zheng Y, Lv T, Wu J, Lyu Y. Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis. Sci Rep. 2022;12(1):14453. https://doi.org/10.1038/s41598-022-18776-7
  63. Stahl SM. Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). Cambridge University Press. 2013.
  64. Varga AW, Ducca EL, Kishi A, et al. Effects of aging on slow-wave sleep dynamics and human spatial navigational memory consolidation. Neurobiol Aging. 2016;42:142-149. 
  65. Shamim SA, Warriach ZI, Tariq MA, et al. Insomnia: Risk Factor for Neurodegenerative Diseases. Cureus. 2019;11(10):e6004. https://doi.org/10.7759/cureus.6004
  66. Wang J, Chen X, Liao J, et al. The influence of non-breathing-related sleep fragmentation on cognitive function in patients with cerebral small vessel disease. Neuropsychiatr Dis Treat. 2019;15:1009-1014. https://doi.org/10.2147/NDT.S193869
  67. Wang J, Liu S, Zhao C, et al. Effects of Trazodone on Sleep Quality and Cognitive Function in Arteriosclerotic Cerebral Small Vessel Disease Comorbid With Chronic Insomnia. Front Psychiatry. 2020;11:620. 
  68. La AL, Walsh CM, Neylan TC, et al. Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers. J Alzheimers Dis. 2019;67(3):911-921. 
  69. Smales ET, Edwards BA, Deyoung PN, et al. Trazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold. Ann Am Thorac Soc. 2015;12(5):758-764.  https://doi.org/10.1513/AnnalsATS.201408-399OC
  70. Shams-Alizadeh N, Maroufi A, Asadi Z, et al. Trazodone as an Alternative Treatment for Neuroleptic-Associated Akathisia: A Placebo-Controlled, Double-Blind, Clinical Trial. J Clin Psychopharmacol. 2020;40(6):611-614.  https://doi.org/10.1097/JCP.0000000000001286
  71. Ribosa-Nogué R, Pagonabarraga J, Kulisevsky J. Efficacy of trazodone in antipsychotic-induced akathisia resistant to conventional treatment. Parkinsonism Relat Disord. 2012;18(7):902-903.  https://doi.org/10.1016/j.parkreldis.2012.04.001
  72. Stryjer R, Rosenzcwaig S, Bar F, et al. Trazodone for the treatment of neuroleptic-induced acute akathisia: a placebo-controlled, double-blind, crossover study. Clin Neuropharmacol. 2010;33(5):219-222.  https://doi.org/10.1097/WNF.0b013e3181ee7f63

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