Психиатрия Психиатрия и психофармакотерапия им. П.Б. Ганнушкина
№03 2021

Тразодон: грани клинической эффективности №03 2021

Номера страниц в выпуске:40-47
Резюме
Тразодон был впервые одобрен для лечения депрессии у взрослых около 40 лет назад. В клинических исследованиях тразодон продемонстрировал эффективность, сравнимую с другими классами антидепрессантов (ТЦА, СИОЗС(Н) и др.). Тразодон позволяет избежать наблюдаемого при приеме СИОЗС(Н) негативного воздействия на сексуальные функции и сон, что особенно важно для поддержания длительной приверженности лечению и высокого качества жизни пациентов. В этом обзоре описывается механизм действия тразодона и резюмируются его положительные эффекты при лечении различных психических и медицинских состояний, таких как депрессия, бессонница, обструктивное апноэ сна, тревожные расстройства, бензодиазепиновая зависимость, сексуальная дисфункция, когнитивное снижение у пожилых и акатизия. Несмотря на эффективность тразодона при лечении множества состояний, для которых он часто используется в клинической практике, многие из таких показаний не являются официально одобренными, поскольку необходимо проведение дорогостоящих полномасштабных регистрационных клинических исследований, что для препаратов с истекшей патентной защитой является крайне маловероятным.
Ключевые слова: тразодон, депрессия, механизм действия, off-label.
Для цитирования: Н.Н. Петрова, Ф.Ш. Шагиахметов, Р.Р. Борукаев. Тразодон: грани клинической эффективности. Психиатрия и психофармакотерапия. 2021; 3: 40–46.
Список исп. литературыСкрыть список
1. Калинченко С.Ю., Авадиева Н.Э. Современная фармакотерапия
женских сексуальных дисфункций. Лечащий врач, №08, 2009 С: 78-
80
2. Ahmadi SA, Sabahi M, Haddadi R. The effect of acute and repeated administration
of buspirone, 8-OHDPAT and fluoxetine on haloperidol-induced
extrapyramidal symptoms. Neuropsychopharmacol Hung. 2019
Jun;21(2):59-68. PMID: 31378723.
3. Albert U, Lamba P, Stahl SM. Early response to trazodone once-a-day in
major depressive disorder: review of the clinical data and putative mechanism
for faster onset of action. CNS Spectr. 2021 Mar 18:1-11. doi:
10.1017/S1092852921000304. Epub ahead of print. PMID: 33731232.
4. Ansseau M, De Roeck J. Trazodone in benzodiazepine dependence. J Clin
Psychiatry. 1993 May;54(5):189-91. PMID: 8509349
5. Ashford JWJW. Treatment of Alzheimer’s Disease: Trazodone, Sleep,
Serotonin, Norepinephrine, and Future Directions. Journal of Alzheimer's
disease: JAD. 2019. 67(3):923-930. DOI:10.3233/JAD-181106
6. Atmaca M. Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction:
Current Management Perspectives. Neuropsychiatr Dis Treat.
2020 Apr 20;16:1043-1050. doi: 10.2147/NDT.S185757. PMID: 32368066;
PMCID: PMC7182464.
7. 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.
doi:10.3389/fnana.2017.00101
8. Bala A, Nguyen HMT, Hellstrom WJG. Post-SSRI Sexual Dysfunction: A
Literature Review. Sex Med Rev. 2018 Jan;6(1):29-34. doi:
10.1016/j.sxmr.2017.07.002. Epub 2017 Aug 1. PMID: 28778697.
9. Beasley CM, Dornseif BE, Pultz JA, Bosomworth JC, Sayler ME. Fluoxetine
versus trazodone: efficacy and activating-sedating effects. J Clin Psychiatry.
1991;52(7):294–299.
10. Bull, S. A., Hunkeler, E. M., Lee, J. Y., Rowland, C. R., Williamson, T. E.,
Schwab, J. R., & Hurt, S. W. (2002). Discontinuing or Switching Selective
Serotonin-Reuptake Inhibitors. Annals of Pharmacotherapy, 36(4), 578–
584. doi:10.1345/aph.1a254
11. Buoli M, Rovera C, Pozzoli SM et al. Is trazodone more effective than
clomipramine in major depressed outpatients? A single-blind study with
intravenous and oral administration. CNS Spectr 2017; 30: 1–7.
12. Cheng WM, Lin TP, Lin AT, Chen KK, Chen TJ. A nationwide population
study of trazodone use in urology patients. J Chin Med Assoc. 2013
Aug;76(8):432-7. doi: 10.1016/j.jcma.2013.05.002. Epub 2013 Jun 17.
PMID: 23786837.
13. Clayton A, Pradko J, Croft H, et al. Prevalence of sexual dysfunction
among newer antidepressants. J Clin Psychiatry. 2002;63:357Y366
14. Cojocariu SA, Maștaleru A, Sascău RA, Stătescu C, Mitu F, Leon-Constantin
MM. Neuropsychiatric Consequences of Lipophilic Beta-Blockers.
Medicina (Kaunas). 2021 Feb 9;57(2):155. doi: 10.3390/medicina
57020155. PMID: 33572109; PMCID: PMC7914867.
15. Devulapalli KK, Nasrallah HA. An analysis of the high psychotropic offlabel
use in psychiatric disorders the majority of psychiatric diagnoses
have no approved drug. Asian J Psychiatr. 2009;2:29–36.
16. Dremencov E, Mansari M, Blier P. Effects of sustained serotonin reuptake
inhibition on the firing of dopamine neurons in the rat ventral tegmental
area. J Psychiatry Neurosci 2009;34(3)
17. EMA. New product information wording—extracts from PRAC recommendations
on signals. 2019. https://www.ema.europa.eu/en/documents/
other/new-product-informationwording-extracts-prac-recommen
dations-signals-adopted-13-16-may-2019-prac_en.pdf
18. Etchecopar-Etchart D, Korchia T, Loundou A, Llorca PM, Auquier P,
Lançon C, Boyer L, Fond G. Comorbid Major Depressive Disorder in Schizophrenia:
A Systematic Review and Meta-Analysis. Schizophr Bull. 2021 Mar
16;47(2):298-308. doi: 10.1093/schbul/sbaa153. PMID: 33252130.
19. 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. doi:10.1007/s40263-012-0010-5
20. Fagiolini A, Albert U, Ferrando L, et al. A randomized, double-blind study
comparing the efficacy and safety of trazodone once-a-day and venlafaxine
extended-release for the treatment of patients with major depressive disorder.
Int Clin Psychopharmacol. 2020;35(3):137-146. doi:10.1097/
YIC.0000000000000304
21. Fink HA, MacDonald R, Rutks IR, Wilt TJ. Trazodone for erectile dysfunction:
a systematic review and meta-analysis. BJU Int. 2003
Sep;92(4):441-6. doi: 10.1046/j.1464-410x.2003.04358.x. PMID: 12930437
22. Florkowski A, Gruszczyński W, Gałecki P, Zboralski K, Kołodziejska I,
Mikołajczyk I. Trazodon i wenlafaksyna w leczeniu zaburzeń depresyjnych
[Trazodone and venlafaxine in treatment of depressive disorders]. Pol
Merkur Lekarski. 2005 May;18(107):556-9. Polish. PMID: 16161955.
23. Goff DC, Midha KK, Brotman AW, McCormick S, Waites M, Amico ET.
An open trial of buspirone added to neuroleptics in schizophrenic patients.
J Clin Psychopharmacol. 1991 Jun;11(3):193-7. PMID: 2066458.
24. Gould S., Friedman L.F. (6 October 2016). "Antidepressant use is rising
sharply around the world". Business Insider. Archived from the original
on 11 May 2019. Retrieved 11 May 2019.
25. 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.
doi:10.1126/sciadv.aav5447
26. Heinzer RC, White DP, Jordan AS, et al. Trazodone increases arousal
threshold in obstructive sleep apnoea. Eur Respir J. 2008;31(6):1308-1312.
doi:10.1183/09031936.00067607
27. Helfer B., Samara M.T., Huhn M., Klupp E., Leucht C., Zhu Y., Engel R.R.,
Leucht S. Efficacy and Safety of Antidepressants Added to Antipsychotics
for Schizophrenia: A Systematic Review and Meta-Analysis. Am J Psychiatry
2016 Sep 1;173(9):876-86;
28. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste
H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular
pathway facilitates CSF flow through the brain parenchyma and
the clearance of interstitial solutes, including amyloid β. Sci Transl Med.
2012 Aug 15;4(147):147ra111. doi: 10.1126/scitranslmed.3003748. PMID:
22896675; PMCID: PMC3551275.
29. Kasper S, Olivieri L, Di Loreto G, Dionisio P. A comparative, randomised,
double-blind study of trazodone prolonged-release and paroxetine in the
treatment of patients with major depressive disorder. Curr Med Res Opin.
2005 Aug;21(8):1139-46
30. Kennedy, S. H., & Rizvi, S. (2009). Sexual Dysfunction, Depression, and
the Impact of Antidepressants. Journal of Clinical Psychopharmacology,
29(2), 157–164. doi:10.1097/jcp.0b013e31819c76e9
31. Koek W, Vacher B, Cosi C, Assié MB, Patoiseau JF, Pauwels PJ, Colpaert
FC. 5-HT1A receptor activation and antidepressant-like effects: F 13714
has high efficacy and marked antidepressant potential. Eur J Pharmacol.
2001 May 25;420(2-3):103-12. doi: 10.1016/s0014-2999(01)01011-1.
PMID: 11408031.
32. 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
33. Malhotra A, Jordan A. The importance of arousal in obstructive sleep
apnea-updates from the American Thoracic Society 2016. J Thorac Dis.
2016;8(Suppl 7):S542-S544. doi:10.21037/jtd.2016.06.81
34. Mangano G, Mancini F, Durando L, Ragni L. Early onset of action for trazodone
antidepressant activity: insight into potential molecular mechanism.
Eur Neuropsychopharmacol. 2020;40(Suppl 1):S457-S458.
35. Moss LE, Neppe VM, Drevets WC. Buspirone in the treatment of tardive
dyskinesia. J Clin Psychopharmacol. 1993 Jun;13(3):204-9. PMID:
8102622.
36. Munizza et al. A comparative, randomized, double-blind study of trazodone
prolonged-release and sertraline in the treatment of major depressive
disorder. Curr Med Res Opin. 2006 Sep;22(9):1703-13
37. O'Brien PL., Cummings N., Mark TL. Off-Label Prescribing of Psychotropic
Medication, 2005-2013: An Examination of Potential Influences.
Psychiatr Serv. 2017 Jun 1;68(6):549-558. doi: 10.1176/appi.ps.
201500482. Epub 2017 Jan 17.
38. Odagaki, Y., Toyoshima, R., & Yamauchi, T. (2005). Trazodone and its
active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A
receptors assessed by [35S]GTPγS binding. Journal of Psychopharmacology,
19(3), 235–241
39. Padala PR, Padala KP, Majagi AS, Garner KK, Dennis RA, Sullivan DH.
Selective serotonin reuptake inhibitors-associated apathy syndrome: A
cross sectional study. Medicine (Baltimore). 2020;99(33):e21497.
doi:10.1097/MD.0000000000021497
40. Papakostas GI, Fava M. A meta-analysis of clinical trials comparing the
serotonin (5HT)-2 receptor antagonists trazodone and nefazodone with
selective serotonin reuptake inhibitors for the treatment of major depressive
disorder. Eur Psychiatry 2007; 22 (7): 444–7.
41. Popovic D, Vieta E, Fornaro M, Perugi G. Cognitive tolerability following
successful long term treatment of major depression and anxiety disorders
with SSRi antidepressants. J Affect Disord. 2015 Mar 1;173:211-5. doi:
10.1016/j.jad.2014.11.008. Epub 2014 Nov 15. PMID: 25462418.
42. Poyurovsky M, Weizman A. Treatment of Antipsychotic-Induced
Akathisia: Role of Serotonin 5-HT2a Receptor Antagonists. Drugs. 2020
Jun;80(9):871-882. doi: 10.1007/s40265-020-01312-0. PMID: 32385739.
43. Pyke RE. Trazodone in Sexual Medicine: Underused and Overdosed? Sex
Med Rev. 2020 Apr;8(2):206-216. doi: 10.1016/j.sxmr.2018.08.003. Epub
2018 Oct 17. PMID: 30342856
44. 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. doi:10.3390/brainsci10110868
45. Reisman, Y. (2020). Post-SSRI sexual dysfunction. BMJ 2020;368:m754.
doi:10.1136/bmj.m754
46. Rickels K, Downing R, Schweizer E, Hassman H. Antidepressants for the
treatment of generalized anxiety disorder: a placebo-controlled comparison
of imipramine, trazodone, and diazepam. Arch Gen Psychiatry.
1993;50(11):884–895. doi: 10.1001/archpsyc.1993.01820230054005
47. Rickels K, et al. Trazodone and valproate in patients discontinuing longterm
benzodiazepine therapy: effects on withdrawal symptoms and taper
outcome. Psychopharmacology (Berl). 1999 Jan;141(1):1-5
48. Ribosa-Nogué R, Pagonabarraga J, Kulisevsky J. Efficacy of trazodone in
antipsychotic-induced akathisia resistant to conventional treatment.
Parkinsonism Relat Disord. 2012 Aug;18(7):902-3. doi: 10.1016/
j.parkreldis.2012.04.001. Epub 2012 Apr 29. PMID: 22548708.
49. Rosenberg KP, Bleiberg KL, Koscis J, Gross C. A survey of sexual side effects
among severely mentally ill patients taking psychotropic medications:
impact on compliance. J Sex Marital Ther. 2003 Jul-Aug;29(4):289-96. doi:
10.1080/00926230390195524. PMID: 14504017.
50. Rothmore, J. (2020). Antidepressant‐induced sexual dysfunction. Medical
Journal of Australia. Volume212, Issue7, April 2020, Pages 329-334
doi:10.5694/mja2.50522
51. Sands SA, Terrill PI, Edwards BA, et al. Quantifying the Arousal Threshold
Using Polysomnography in Obstructive Sleep Apnea. Sleep.
2018;41(1):zsx183. doi:10.1093/sleep/zsx183
52. Sansone RA, Sansone LA, SSRI-induced indifference, Psychiatry (Edgemont)
2010;7(10):14–18
53. Scaglione F et al. La gestione dell’insonnia nel paziente anziano: dalla farmacologia
alla depressione sottosoglia. Riv Psichiatr 2018; 53:5-17.
54. Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to
antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009
Jun;29(3):259-66. doi: 10.1097/JCP.0b013e3181a5233f. PMID: 19440080.
55. Settimo L, Taylor D. Evaluating the dose-dependent mechanism of action
of trazodone by estimation of occupancies for different brain neurotransmitter
targets. J Psychopharmacol. 2018;32(1):96–104. doi:10.1177/
0269881117742101
56. Shams-Alizadeh N, Maroufi A, Asadi Z, Rahmani K, Hassanzadeh K. Trazodone
as an Alternative Treatment for Neuroleptic-Associated Akathisia:
A Placebo-Controlled, Double-Blind, Clinical Trial. J Clin Psychopharmacol.
2020 Nov/Dec;40(6):611-614. doi: 10.1097/JCP.0000000000001286. PMID:
33044356.
57. Simon JA, Thorp J, Millheiser L. Flibanserin for Premenopausal Hypoactive
Sexual Desire Disorder: Pooled Analysis of Clinical Trials. J Womens
Health (Larchmt). 2019 Jun;28(6):769-777. doi: 10.1089/jwh.2018.7516.
Epub 2019 Feb 1. PMID: 30707049.
58. Singh S.P. et al. Efficacy of antidepressants in treating the negative symptoms
of chronic schizophrenia: meta-analysis. Br J Psychiatry. 2010
Sep;197(3):174-9. doi: 10.1192/bjp.bp.109.067710.
59. Smales ET, Edwards BA, Deyoung PN, McSharry DG, Wellman A, Velasquez
A, Owens R, Orr JE, Malhotra A. Trazodone Effects on Obstructive
Sleep Apnea and Non-REM Arousal Threshold. Ann Am Thorac Soc.
2015 May;12(5):758-64. doi: 10.1513/AnnalsATS.201408-399OC. PMID:
25719754; PMCID: PMC4418332.
60. Soyka, M. (2017). Treatment of Benzodiazepine Dependence. New England
Journal of Medicine, 376(12), 1147–1157. doi:10.1056/nejmra
1611832
61. Stahl SM. Targeting circuits of sexual desire as a treatment strategy for hypoactive
sexual desire disorder. J Clin Psychiatry. 2010 Jul;71(7):821-2.
doi: 10.4088/JCP.10bs06117blu. PMID: 20667289
62. Stryjer R, Spivak B, Strous RD, et al. Trazodone for the treatment of sexual
dysfunction induced by serotonin reuptake inhibitors: a preliminary openlabel
study. Clinical Neuropharmacology. 2009 Mar-Apr;32(2):82-84.
DOI: 10.1097/wnf.0b013e31816d1cdc.
63. 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
64. 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
65. Weisler RH, Johnston JA, Lineberry CG, et al. Comparison of bupropion
and trazodone for the treatment of major depression. J Clin Psychopharmacol.
1994;14(3):170–179.
66. Wichniak A, Wierzbicka A, Walęcka M, Jernajczyk W. Effects of Antidepressants
on Sleep. Curr Psychiatry Rep. 2017;19(9):63. Published 2017
Aug 9. doi:10.1007/s11920-017-0816-4
67. Wong J, Motulsky A, Abrahamowicz M, et al. Off-label indications for antidepressants
in primary care: descriptive study of prescriptions from an
indication based electronic prescribing system. BMJ 2017;356:j603.
68. Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J,
Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M.
Sleep drives metabolite clearance from the adult brain. Science. 2013 Oct
18;342(6156):373-7. doi: 10.1126/science.1241224. PMID: 24136970;
PMCID: PMC3880190.
69. Yan T, Qiu Y, Yu X, Yang L. Glymphatic Dysfunction: A Bridge Between
Sleep Disturbance and Mood Disorders. Front Psychiatry. 2021;12:658340.
Published 2021 May 7. doi:10.3389/fpsyt.2021.658340
70. Zavoianu M et al. Efficacy of trazodone in patients diagnosed with generalised
anxiety disorder and benzodiazepine dependence. European Neuropsychopharmacology,
Volume 19, Supplement 3, September 2009,
Pages S617-S618
71. Zhang L, Xie WW, Li LH, et al. Efficacy and safety of prolonged-release
trazodone in major depressive disorder: a multicenter, randomized, double-
blind, flexible-dose trial. Pharmacology. 2014;94(5–6):199–206.
doi:10.1159/000368559.
72. Zhang H et al. A control study on treatment for benzodiazepine dependence
with trazodone / CJCNN 2013(5):411-415 DOI: 10.3969/j.issn.1672-
6731.2013.05.011
Количество просмотров: 1548
Предыдущая статьяЭффективность, переносимость и безопасность карипразина при расстройствах биполярного спектра
Следующая статьяПсихофармакотерапия и психотерапия патологических телесных сенсаций в челюстно-лицевой области
Прямой эфир