정신신체의학 (Korean Journal of Psychosomatic Medicine)

한국정신신체의학회 (Korean Psychosomatic Society)
권호 표지
DOI QR코드

DOI QR Code

혈소판기능분석기를 이용한 선택적 세로토닌 재흡수 억제제와 세로토닌 노르에피네프린 재흡수 억제제의 출혈 경향성 비교

Comparison of Bleeding Tendency Between Selective Serotonin Reuptake Inhibitors and Serotonin Norepinephrine Reuptake Inhibitors Using Platelet Function Analyzer

  • 구승모 (인제대학교 의과대학 일산백병원 정신건강의학교실) ;
  • 김현 (인제대학교 의과대학 일산백병원 정신건강의학교실) ;
  • 이강준 (인제대학교 의과대학 일산백병원 정신건강의학교실)
  • Koo, Seung Mo (Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine) ;
  • Kim, Hyun (Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine) ;
  • Lee, Kang Joon (Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine)
  • 투고 : 2021.09.02
  • 심사 : 2021.10.14
  • 발행 : 2021.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

연구목적 본 연구는 주요우울장애 환자들을 대상으로, 혈소판기능분석기(Platelet Function Analyzer, PFA-100)를 사용하여 선택적 세로토닌 재흡수 억제제(Selective Serotonin Reuptake Inhibitors, SSRI)와 세로토닌 노르에피네프린 재흡수 억제제(Serotonin Norepinephrine Reuptake Inhibitors, SNRI)의 출혈 경향성을 분석하고, 두 군 사이의 차이를 비교 분석하고자 하였다. 방 법 본 연구는 단일 기관에서 시행된 전향적 개방연구로 DSM-5 진단기준에 의해 주요우울장애로 진단받은 총 41명을 대상으로 하였다. 대상군을 무작위 배정에 따라 각각 SSRI (Escitalopram) 투여군과, SNRI (Duloxetine) 투여군으로 분류하였다. 각 항우울제를 투여 받기 전과 6주가 지난 시점에 혈소판기능분석기(Platelet Function Analyzer, PFA-100)를 이용하여 폐색시간(Closure Time, CT)을 측정하였다. 특정 항우울제가 폐색시간에 영향을 미치는지 알아보기 위해 각 군 내에서 대응표본 t-검정(Paired t-test)을 시행하였고, 두 군 사이에 혈소판 기능의 상대적인 변화를 확인하기 위해 공분산 분석(Analysis Of Covariance, ANCOVA)을 시행하여 두 군의 폐색시간의 변화를 비교 분석하였다. 결 과 SSRI군과 SNRI군에서 약물 투여 전과 6주후 폐색시간(CEPI-CT, CADP-CT)에 대한 유의한 변화는 없었고, 두 군 간의 폐색시간 변화량에도 차이가 없었다. 결 론 혈소판기능분석기(Platelet Function Analyzer, PFA-100)를 통해 SSRI인 Escitalopram과 SNRI인 Duloxetine간의 출혈경향성에 차이가 없음을 보였다. 향후 다양한 항우울제를 대상으로 출혈경향성에 대한 추가적인 대규모 연구가 필요할 것으로 보인다.

Objectives : The purpose of this study is to compare bleeding tendency of selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) using platelet function analyzer (PFA-100) in patients with major depressive disorder. Methods : This study is a prospective open-label study conducted by a single institution. A total of 41 subjects diagnosed with major depressive disorder under the DSM-5 diagnostic criteria participated in this study. The subjects were classified into SSRI (escitalopram) groups and SNRI (duloxetine) groups, respectively, according to random assignments. The closure time (CT) was measured using a platelet function analyzer (PFA-100) before each antidepressant was administered and after 6 weeks. Paired-sample t-test was conducted within each group to determine whether a specific antidepressant had an effect on closure time. In order to confirm the relative change in platelet function between the two groups, an independent sample t-test was conducted to compare and analyze the change in closure time between the two groups. Results : There was no significant changes in closure time (CEPI-CT, CADP-CT) before and 6 weeks after drug administration in the SSRI and SNRI groups, and there was no difference in the amount of changes in closure time between the two groups. Conclusions : Our results showed no difference in bleeding tendency between SSRI and SNRI. This study suggests that further large-scale studies on bleeding tendency for various antidepressants are needed in the future.

키워드

참고문헌

  1. World Health Organization. Depression and other common mental disorders: global health estimates. World Health Organization;2017. Available from: https://apps.who.int/iris/bitstream/handle/10665/254610/WHO-MSD-MER-2017.2-eng.pdf.
  2. Organization for Economic Co-operation and Development. Health at a Glance 2017: OECD Indicators. Paris: OECD Publishing;2017. Available from: https://doi.org/10.1787/health_glance-2017-en.
  3. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:593-602. https://doi.org/10.1001/archpsyc.62.6.593
  4. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1789-1858. https://doi.org/10.1016/s0140-6736(18)32279-7
  5. Rui P, Hing E, Okeyode T. National Ambulatory Medical Care Survey: 2014 state and national summary tables. Available from: https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2014_namcs_web_tables.pdf.
  6. Kim SJ. Prescription pattern of antidepressants among the Korean patients with depression (thesis). Seoul: Seoul National University;2018.
  7. Lee KK. Adverse effects and pharmacological management of newer antidepressants: focusing on common but under-recognized adverse effect. Korean J Psychopharmacol 2014;25:11-20
  8. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, ed 3. Arlington: American Psychiatric Association; 2010. Available from: http://www.psych.org/guidelines/mdd2010.
  9. Park SC, Sung SH, Han KM, Won ES, Lee HY, Paik JW, Jeon HJ, Lee MS, Shim SH, Ko YH, Lee KJ, Han CS, Ham BJ, Choi JH, Lee HY, Hwang TY, Oh KS, Park YC, Lee MS, Hahn SW. Evidence-based Korean pharmacological treatment guideline for depression, revised edition (I): initial choice of antidepressant treatment. J Korean Neuropsychiatr Assoc 2013;52:253-262. https://doi.org/10.4306/jknpa.2013.52.4.253
  10. Reid S, Barbui C. Long term treatment of depression with selective serotonin reuptake inhibitors and newer antidepressants. BMJ 2010;340:c1468. https://doi.org/10.1136/bmj.c1468
  11. Khawam EA, Laurencic G, Malone DA Jr. Side effects of antidepressants: an overview. Cleve Clin J Med 2006;73:351- 353, 356-361. https://doi.org/10.3949/ccjm.73.4.351
  12. Laporte S, Chapelle C, Caillet P, Beyens MN, Bellet F, Delavenne X, Mismetti P, Bertoletti L. Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies. Pharmacol Res 2017; 118:19-32. https://doi.org/10.1016/j.phrs.2016.08.017
  13. Powell KK, Wang W, Kelleher KJ, O'Brien SH. Use of SSRIs not associated with increased bleeding events in children: an analysis of the michigan medicaid database from 2000-2003. Blood 2008;112:2389. https://doi.org/10.1182/blood.v112.11.2389.2389
  14. Quinn GR, Hellkamp AS, Hankey GJ, Becker RC, Berkowitz SD, Breithardt G, Fava M, Fox KAA, Halperin JL, Mahaffey KW, Nessel CC, Patel MR, Piccini JP, Singer DE. Selective serotonin reuptake inhibitors and bleeding risk in anticoagulated patients with atrial fibrillation: an analysis from the ROCKET AF trial. J Am Heart Assoc 2018;7:e008755. https://doi.org/10.1161/jaha.118.008755
  15. Laursen SB, Leontiadis GI, Stanley AJ, Hallas J, Schaffalitzky de Muckadell OB. The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding. Aliment Pharmacol Ther 2017;46:355-363. https://doi.org/10.1111/apt.14153
  16. Pletscher A. Metabolism, transfer and storage of 5-hydroxytryptamine in blood platelets. Br J Pharmacol Chemother 1968; 32:1-16. https://doi.org/10.1111/j.1476-5381.1968.tb00423.x
  17. De Clerck F. The role of serotonin in thrombogenesis. Clin Physiol Biochem 1990;8 Suppl 3:40-49.
  18. Halperin D, Reber G. Influence of antidepressants on hemostasis. Dialogues Clin Neurosci 2007;9:47-59. https://doi.org/10.31887/DCNS.2007.9.1/dhalperin
  19. De Abajo FJ. Effects of selective serotonin reuptake inhibitors on platelet function: mechanisms, clinical outcomes and implications for use in elderly patients. Drugs Aging 2011;28:345-367. https://doi.org/10.2165/11589340-000000000-00000
  20. Opatrny L, Delaney JA, Suissa S. Gastro-intestinal haemorrhage risks of selective serotonin receptor antagonist therapy: a new look. Br J Clin Pharmacol 2008;66:76-81. https://doi.org/10.1111/j.1365-2125.2008.03154.x
  21. Dall M, Schaffalitzky de Muckadell OB, Lassen AT, Hansen JM, Hallas J. An association between selective serotonin reuptake inhibitor use and serious upper gastrointestinal bleeding. Clin Gastroenterol Hepatol 2009;7:1314-1321. https://doi.org/10.1016/j.cgh.2009.08.019
  22. De Abajo FJ, Garcia-Rodriguez LA. Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents. Arch Gen Psychiatry 2008;65:795-803. https://doi.org/10.1001/archpsyc.65.7.795
  23. Cheng YL, Hu HY, Lin XH, Luo JC, Peng YL, Hou MC, Lin HC, Lee FY. Use of SSRI, But Not SNRI, increased upper and lower gastrointestinal bleeding: a nationwide population-based cohort study in Taiwan. Medicine (Baltimore) 2015; 94:e2022. https://doi.org/10.1097/md.0000000000002022
  24. Francis J, Francis D, Larson L, Helms E, Garcia M. Can the Platelet Function Analyzer (PFA)-100 test substitute for the template bleeding time in routine clinical practice? Platelets 1999;10:132-136. https://doi.org/10.1080/09537109976194
  25. Serebruany VL, Glassman AH, Malinin AI, Atar D, Sane DC, Oshrine BR, Ferguson JJ, O'Connor CM. Selective serotonin reuptake inhibitors yield additional antiplatelet protection in patients with congestive heart failure treated with antecedent aspirin. Eur J Heart Fail 2003;5:517-521. https://doi.org/10.1016/S1388-9842(03)00005-9
  26. Buyukasik Y, Karakus S, Goker H, Haznedaroglu IC, Ozatli D, Sayinalp N, Ozcebe OI, Dundar SV, Kirazli S. Rational use of the PFA-100 device for screening of platelet function disorders and von Willebrand disease. Blood Coagul Fibrinolysis 2002;13:349-353. https://doi.org/10.1097/00001721-200206000-00011
  27. Harrison P, Robinson M, Liesner R, Khair K, Cohen H, Mackie I, Machin S. The PFA-100: a potential rapid screening tool for the assessment of platelet dysfunction. Clin Lab Haematol 2002;24:225-232. https://doi.org/10.1046/j.1365-2257.2002.00451.x
  28. Hergovich N, Aigner M, Eichler HG, Entlicher J, Drucker C, Jilma B. Paroxetine decreases platelet serotonin storage and platelet function in human beings. Clin Pharmacol Ther 2000; 68:435-442. https://doi.org/10.1067/mcp.2000.110456
  29. Kotzailias N, Andonovski T, Dukic A, Serebruany VL, Jilma B. Antiplatelet activity during coadministration of the selective serotonin reuptake inhibitor paroxetine and aspirin in male smokers: a randomized, placebo-controlled, double-blind trial. J Clin Pharmacol 2006;46:468-475. https://doi.org/10.1177/0091270006286432
  30. McCloskey DJ, Postolache TT, Vittone BJ, Nghiem KL, Monsale JL, Wesley RA, Rick ME. Selective serotonin reuptake inhibitors: measurement of effect on platelet function. Transl Res 2008;151:168-172. https://doi.org/10.1016/j.trsl.2007.10.004
  31. Favaloro EJ. Clinical application of the PFA-100. Curr Opin Hematol 2002;9:407-415. https://doi.org/10.1097/00062752-200209000-00004
  32. Cho YU, Chi HS, Jang S, Park CJ. Reconfirmation of preanalytical variables and establishment of reference intervals of platelet function analyzer-100 closure times in Korean adults. Korean J Lab Med 2007;27:318-323.
  33. Movig KL, Janssen MW, de Waal Malefijt J, Kabel PJ, Leufkens HG, Egberts AC. Relationship of serotonergic antidepressants and need for blood transfusion in orthopedic surgical patients. Arch Intern Med 2003;163:2354-2358. https://doi.org/10.1001/archinte.163.19.2354
  34. Sajan F, Conte JV, Tamargo RJ, Riley LH, Rock P, Faraday N. Association of selective serotonin reuptake inhibitors with transfusion in surgical patients. Anesth Analg 2016;123:21-28. https://doi.org/10.1213/ANE.0000000000001319
  35. De Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ 1999;319:1106-1109.
  36. Laine-Cessac P, Shoaay I, Garre JB, Glaud V, Turcant A, Allain P. Study of haemostasis in depressive patients treated with fluoxetine. Pharmacoepidemiol Drug Saf 1998;7(suppl1):S54-S57. https://doi.org/10.1002/(SICI)1099-1557(199808)7:1+3.0.CO;2-Z
  37. Alderman CP, Seshadri P, Ben-Tovim DI. Effects of serotonin reuptake inhibitors on hemostasis. Ann Pharmacother 1996; 30:1232-1234. https://doi.org/10.1177/106002809603001103
  38. Lederbogen F, Weber B, Colla M, Heuser H, Deuschle M, Dempfle CE. Antidepressant treatment and global tests of coagulation and fibrinolysis. J Clin Psychiatry 2001;62:2.
  39. Menys VC, Smith CC, Lewins P, Farmer RD, Noble MI. Platelet 5-hydroxytryptamine is decreased in a preliminary group of depressed patients receiving the 5-hydroxytryptamine re-uptake inhibiting drug fluoxetine. Clin Sci (Lond) 1996;91:87-92. https://doi.org/10.1042/cs0910087
  40. Serebruany VL, Glassman AH, Malinin AI, Nemeroff CB, Musselman DL, van Zyl LT, Finkel MS, Krishnan KR, Gaffney M, Harrison W, Califf RM, O'Connor CM; Sertraline AntiDepressant Heart Attack Randomized Trial Study Group. Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy. Circulation 2003;108:939-944. https://doi.org/10.1161/01.CIR.0000085163.21752.0A
  41. Pollock BG, Laghrissi-Thode F, Wagner WR. Evaluation of platelet activation in depressed patients with ischemic heart disease after paroxetine or nortriptyline treatment. J Clin Psychopharmacol 2000;20:137-140 https://doi.org/10.1097/00004714-200004000-00004
  42. Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, Larkin EC, Liles D, Nugent DJ. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost 1998;24:195-202. https://doi.org/10.1055/s-2007-995840
  43. Hayward CP, Harrison P, Cattaneo M, Ortel TL, Rao AK. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006;4:312-319. https://doi.org/10.1111/j.1538-7836.2006.01771.x
  44. Meijer WE, Heerdink ER, Nolen WA, Herings RM, Leufkens HG, Egberts AC. Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants. Arch Intern Med 2004;164:2367-2370. https://doi.org/10.1001/archinte.164.21.2367
  45. Tatsumi M, Groshan K, Blakely RD, Richelson E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 1997;340: 249-258. https://doi.org/10.1016/S0014-2999(97)01393-9
  46. Castro VM, Gallagher PJ, Clements CC, Murphy SN, Gainer VS, Fava M, Weilburg JB, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH. Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants. BMJ Open 2012;2:e000544. https://doi.org/10.1136/bmjopen-2011-000544
  47. Verdel BM, Souverein PC, Meenks SD, Heerdink ER, Leufkens HG, Egberts TC. Use of serotonergic drugs and the risk of bleeding. Clin Pharmacol Ther 2011;89:89-96. https://doi.org/10.1038/clpt.2010.240
  48. Haubelt H, Anders C, Vogt A, Hoerdt P, Seyfert UT, Hellstern P. Variables influencing Platelet Function Analyzer-100 closure times in healthy individuals. Br J Haematol 2005;130: 759-767. https://doi.org/10.1111/j.1365-2141.2005.05680.x
  49. Abdelmalik N, Ruhe HG, Barwari K, van den Dool EJ, Meijers JC, Middeldorp S, Buller HR, Schene AH, Kamphuisen PW. Effect of the selective serotonin reuptake inhibitor paroxetine on platelet function is modified by a SLC6A4 serotonin transporter polymorphism. J Thromb Haemost 2008; 6:2168-2174. https://doi.org/10.1111/j.1538-7836.2008.03196.x
  50. Atar D, Malinin A, Pokov A, van Zyl L, Frasure-Smith N, Lesperance F, Serebruany VL. Antiplatelet properties of escitalopram in patients with the metabolic syndrome: a doseranging in vitro study. Neuropsychopharmacology 2007;32: 2369-2374. https://doi.org/10.1038/sj.npp.1301355