Рекуррентная депрессия и выраженность суставной деструкции у больных ревматоидным артритом
Рекуррентная депрессия и выраженность суставной деструкции у больных ревматоидным артритом
Абрамкин А.А., Лисицына Т.А., Вельтищев Д.Ю. и др. Рекуррентная депрессия и выраженность суставной деструкции у больных ревматоидным артритом. Терапевтический архив. 2020; 92 (5): 22–32. DOI: 10.26442/00403660.2020.05.000624
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Аннотация
Цель. Оценить влияние расстройств тревожно-депрессивного спектра (РТДС) на прогрессирование деструкции суставов у больных ревматоидным артритом (РА).
Материалы и методы. В исследование включены 128 пациентов с достоверным диагнозом РА, 87% – женщины, средний возраст 47,4±11,3 года, медиана длительности РА – 96 [48; 228] мес. При включении в исследование у большинства пациентов активность по DAS28 высокая (n=48, 37,5%) или умеренная (n=56, 43,7%). С целью оценки выраженности боли и ее воздействия на отдельные аспекты жизни использовали шкалу Brief Pain Inventory (BPI). РТДС диагностированы психиатром с применением метода полуструктурированного интервью в соответствии с критериями Международной классификации болезней 10-го пересмотра у 123 (96,1%) пациентов. Выраженность депрессивных расстройств определяли по шкале Монтгомери–Асберг, тревоги – по шкале тревоги Гамильтона. Всем пациентам с РТДС предложена психофармакотерапия (ПФТ), 52 согласились на лечение, 71 отказался.
В зависимости от проводимой терапии выделены следующие терапевтические группы: 1-я – базисные противовоспалительные препараты – БПВП (n=39), 2-я – БПВП+ПФТ (n=43), 3-я – БПВП + генно-инженерные биологические препараты – ГИБП (n=32), 4-я – БПВП+ГИБП+ПФТ (n=9). Исходы РА и динамику РТДС через 5 лет наблюдения оценивали у 83 (67,5%) больных. Для оценки влияния показателей, характеризующих РА и динамику стрессовых факторов и психических расстройств на деструктивные изменения в костях и суставах, пациенты разделены по степени деструкции суставов на 2 подгруппы – с максимальной деструкцией (рентгенологическая стадия III и IV и/или остеонекроз) и минимальной деструкцией (I и II рентгенологическая стадия, остеонекрозов нет). Предикторы максимальной суставной деструкции определялись с помощью линейного регрессионного моделирования.
Результаты. По данным регрессионного анализа с максимальной суставной деструкцией через 5 лет ассоциируются: исходно более выраженная максимальная боль по шкале BPI, большая длительность РА и РТДС, исходно клинически значимая усталость, исходное наличие внесуставных проявлений РА, а также рекуррентное депрессивное расстройство через 5 лет наблюдения и терапия только БПВП, без ГИБП и ПФТ.
Заключение. Рекуррентное депрессивное расстройство в отсутствие терапии антидепрессантами является важным предиктором прогрессирования суставной деструкции у больных РА.
Ключевые слова: ревматоидный артрит, рекуррентное депрессивное расстройство, предикторы, рентгенологическая прогрессия, суставная деструкция, антидепрессанты.
Materials and methods. 128 RA-patients were included, 87% were women with a mean age of 47.4±11.3 years and a median of RA duration – 96 [48; 228] months. At the inclusion most patients had moderate (n=56, 43.7%) and severe (n=48, 37.5%) disease activity according to DAS28. Joint destruction was classified as maximal in patients with radiographic stage III, IV and/or osteonecrosis) and minimal in patients with stage I, II and no osteonecrosis. Pain intensity was measured with the BPI (Brief Pain Inventory) scale, severity of fatigue – with fatigue severity scale (FSS), clinically important fatigue was diagnosed in patients with FSS≥4. Anxiety and depressive disorders (ADD) were diagnosed by a licensed psychiatrist in 123 (96.1%) of RA-patients in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A). RA-patients with ADD were divided into the following treatment groups: 1 – сDMARDs (n=39), 2 – сDMARDs+PPT (sertraline or mianserine), n=43,
3 – сDMARDs+bDMARDs (n=32), 4 – сDMARDs+bDMARDs+PPT (sertraline or mianserine), n=9. Biologics treatment duration varied from 1 to 6 years, antidepressants – from 6 to 96 weeks. 83 (67.5%) RA patients were assessed at five-years follow-up. Linear regression analysis was conducted to determine factors associated with maximal join destruction.
Results. According to linear regression analysis, maximal joint destruction at 5 years follow-up was associated with higher baseline BPImax, longer RA and ADD duration, clinically important fatigue at baseline, baseline extraarticular RA manifestations, recurrent depressive disorder at 5-years follow-up and treatment with cDMARDs only.
Conclusion. Recurrent depressive disorder without antidepressant treatment is an important predictor of progression of joint destruction in patients with rheumatoid arthritis.
Keywords: rheumatoid arthritis, recurrent depression, predictors, radiographic progression, joint destruction, antidepressants.
Материалы и методы. В исследование включены 128 пациентов с достоверным диагнозом РА, 87% – женщины, средний возраст 47,4±11,3 года, медиана длительности РА – 96 [48; 228] мес. При включении в исследование у большинства пациентов активность по DAS28 высокая (n=48, 37,5%) или умеренная (n=56, 43,7%). С целью оценки выраженности боли и ее воздействия на отдельные аспекты жизни использовали шкалу Brief Pain Inventory (BPI). РТДС диагностированы психиатром с применением метода полуструктурированного интервью в соответствии с критериями Международной классификации болезней 10-го пересмотра у 123 (96,1%) пациентов. Выраженность депрессивных расстройств определяли по шкале Монтгомери–Асберг, тревоги – по шкале тревоги Гамильтона. Всем пациентам с РТДС предложена психофармакотерапия (ПФТ), 52 согласились на лечение, 71 отказался.
В зависимости от проводимой терапии выделены следующие терапевтические группы: 1-я – базисные противовоспалительные препараты – БПВП (n=39), 2-я – БПВП+ПФТ (n=43), 3-я – БПВП + генно-инженерные биологические препараты – ГИБП (n=32), 4-я – БПВП+ГИБП+ПФТ (n=9). Исходы РА и динамику РТДС через 5 лет наблюдения оценивали у 83 (67,5%) больных. Для оценки влияния показателей, характеризующих РА и динамику стрессовых факторов и психических расстройств на деструктивные изменения в костях и суставах, пациенты разделены по степени деструкции суставов на 2 подгруппы – с максимальной деструкцией (рентгенологическая стадия III и IV и/или остеонекроз) и минимальной деструкцией (I и II рентгенологическая стадия, остеонекрозов нет). Предикторы максимальной суставной деструкции определялись с помощью линейного регрессионного моделирования.
Результаты. По данным регрессионного анализа с максимальной суставной деструкцией через 5 лет ассоциируются: исходно более выраженная максимальная боль по шкале BPI, большая длительность РА и РТДС, исходно клинически значимая усталость, исходное наличие внесуставных проявлений РА, а также рекуррентное депрессивное расстройство через 5 лет наблюдения и терапия только БПВП, без ГИБП и ПФТ.
Заключение. Рекуррентное депрессивное расстройство в отсутствие терапии антидепрессантами является важным предиктором прогрессирования суставной деструкции у больных РА.
Ключевые слова: ревматоидный артрит, рекуррентное депрессивное расстройство, предикторы, рентгенологическая прогрессия, суставная деструкция, антидепрессанты.
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Materials and methods. 128 RA-patients were included, 87% were women with a mean age of 47.4±11.3 years and a median of RA duration – 96 [48; 228] months. At the inclusion most patients had moderate (n=56, 43.7%) and severe (n=48, 37.5%) disease activity according to DAS28. Joint destruction was classified as maximal in patients with radiographic stage III, IV and/or osteonecrosis) and minimal in patients with stage I, II and no osteonecrosis. Pain intensity was measured with the BPI (Brief Pain Inventory) scale, severity of fatigue – with fatigue severity scale (FSS), clinically important fatigue was diagnosed in patients with FSS≥4. Anxiety and depressive disorders (ADD) were diagnosed by a licensed psychiatrist in 123 (96.1%) of RA-patients in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A). RA-patients with ADD were divided into the following treatment groups: 1 – сDMARDs (n=39), 2 – сDMARDs+PPT (sertraline or mianserine), n=43,
3 – сDMARDs+bDMARDs (n=32), 4 – сDMARDs+bDMARDs+PPT (sertraline or mianserine), n=9. Biologics treatment duration varied from 1 to 6 years, antidepressants – from 6 to 96 weeks. 83 (67.5%) RA patients were assessed at five-years follow-up. Linear regression analysis was conducted to determine factors associated with maximal join destruction.
Results. According to linear regression analysis, maximal joint destruction at 5 years follow-up was associated with higher baseline BPImax, longer RA and ADD duration, clinically important fatigue at baseline, baseline extraarticular RA manifestations, recurrent depressive disorder at 5-years follow-up and treatment with cDMARDs only.
Conclusion. Recurrent depressive disorder without antidepressant treatment is an important predictor of progression of joint destruction in patients with rheumatoid arthritis.
Keywords: rheumatoid arthritis, recurrent depression, predictors, radiographic progression, joint destruction, antidepressants.
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11. Lisitsyna TA, Veltishchev DY, Nasonov EL. Stressors and depressive disorders in rheumatic diseases. Rheumatology Science and Practice. 2013;51(2):98-103 (In Russ.) doi: 10.14412/1995-4484-2013-634
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21. Michelsen B, Kristianslund EK, Sexton J, et al. Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR-DMARD study. Ann Rheum Dis. 2017;76(11):1906-10. doi: 10.1136/annrheumdis-2017-211284
22. Abramkin AA. Impact of comorbid mental disorders on the efficiency of therapy in patients with rheumatoid arthritis. Rheumatology Science and Practice. 2016;54(3):339-45 (In Russ.) doi: 10.14412/1995-4484-2016-339-345
23. Matcham F, Ali S, Irving K, et al. Are depression and anxiety associated with disease activity in rheumatoid arthritis? A prospective study. BMC Musculoskelet Dis. 2016;17(1):155. doi: 10.1186/s12891-016-1011-1
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29. Ozgonenel L, Cetin E, Tutun S, et al. The relation of serum vascular endothelial growth factor level with disease duration and activity in patients with rheumatoid arthritis. Clin Rheumatol. 2010;29(5):473-7. doi: 10.1007/s10067-009-1343-4
30. Szekanecz Z, Koch AE. VEGF as an activity marker in rheumatoid arthritis. Int J Clin Rheumatol. 2010;5(3):287-9. doi: 10.2217/IJR.10.24
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33. Cocchi M, Tonello L, Gabrielli F, Pregnolato M. Depression, osteoporosis, serotonin and cell membrane viscosity between biology and philosophical anthropology. Ann Gen Psychiatry. 2011;10:9. doi: 10.1186/1744-859X-10-9
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36. Gururajan A, Clarke G, Dinan TG, Cryan JF. Molecular biomarkers of depression. Neurosci Biobehav Rev. 2016;64:101-33. doi: 10.1016/
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56. Tegethoff M, Stalujanis E, Belardi A, Meinlschmidt G. Chronology of onset of mental disorders and physical diseases in mental-physical comorbidity – A national representative survey of adolescents. PLoS One. 2016;11(10):e0165196. doi: 10.1371/journal.pone.0165196
57. Marrie RA, Walld R, Bolton JM, et al. Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease. Epidemiol Psychiatr Sci. 2017:1-10. doi: 10.1017/S2045796017000579
58. Zhang L, Wang J, Zhang Q, et al. Factors associated with hand joint destruction in Chinese patients with rheumatoid arthritis. BMC Musculoskelet Dis. 2017;18(1):211. doi: 10.1186/s12891-017-1548-7
59. Karpouzas GA, Draper T, Moran R, et al. Trends in functional disability and determinants of clinically meaningful change over time in Hispanics with Rheumatoid arthritis in the United States. Arthritis Care Res (Hoboken). 2016;69(2):294-8. doi: 10.1002/acr.22924
60. Wolfe F, Michaud K. Predicting depression in rheumatoid arthritis: The signal importance of pain extent and fatigue, and comorbidity. Arthritis Care Res. 2009;61(5):667-73. doi: 10.1002/art.24428
2. Favalli EG, Becciolini A, Biggioggero M. Structural integrity versus radiographic progression in rheumatoid arthritis. RMD Open. 2015;1(Suppl. 1):e000064. doi: 10.1136/rmdopen-2015-000064
3. Schett G, Gravallese E. Bone erosion in rheumatoid arthritis: Mechanisms, diagnosis and treatment. Nat Rev Rheumatol. 2012;8(11):656-64. doi: 10.1038/nrrheum.2012.153
4. Чичасова Н.В. Деструкция хряща при ревматоидном артрите, связь с функциональными нарушениями. Совр. ревматология. 2014;(4):60-71 [Chichasova NV. Cartilage destruction in rheumatoid arthritis, its association with functional impairments. Modern Rheumatology Journal. 2014;8(4):60-71 (In Russ.)]. doi: 10.14412/2074-2711-2014-4-60-71
5. Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-77. doi: 10.1136/annrheumdis-2016-210715
6. Dougados M, Soubrier M, Antunez A, et al. Prevalence of comorbidities in rheumatoid arthritis (ra) and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis. 2013;72:600.
7. Лисицына Т.А., Вельтищев Д.Ю. Психические расстройства у больных ревматическими заболеваниями: диагностика и лечение. Научно-практич. ревматология. 2015;53(5):512-21 [Lisitsyna TA, Veltishchev DY. Mental disorders in patients with rheumatic diseases: diagnosis and treatment. Rheumatology Science and Practice. 2015;53(5):512-21 (In Russ.)]. doi: 10.14412/1995-4484-2015-512-521
8. Soósová MS, Macejová Ž, Zamboriová M, Dimunová L. Anxiety and depression in Slovak patients with rheumatoid arthritis. J Ment Heal. 2017 Feb;26(1):21-7. doi: 10.1080/09638237.2016.1244719
9. Gåfvels C, Hägerström M, Rane K, et al. Depression and anxiety after 2 years of follow-up in patients diagnosed with diabetes or rheumatoid arthritis. Heal Psychol Open. 2016;3(2):205510291667810. doi: 10.1177/2055102916678107
10. Fiest KM, Hitchon CA, Bernstein CN, et al. Systematic Review and Meta-analysis of Interventions for Depression and Anxiety in Persons With Rheumatoid Arthritis. JCR J Clin Rheumatol. 2017;23(Issue 8): 425-34. doi: 10.1097/RHU.0000000000000489
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13. Rupp I, Boshuizen HC, Dinant HJ, et al. Disability and health-related quality of life among patients with rheumatoid arthritis: Association with radiographic joint damage, disease activity, pain, and depressive symptoms. Scand J Rheumatol. 2006;35(3):175-81. doi: 10.1080/03009740500343260
14. Euesden J, Matcham F, Hotopf M, et al. The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis. Psychosom Med. 2017;79(6):638-45. doi: 10.1097/PSY.0000000000000462
15. Kronisch C, McLernon DJ, Dale J, et al. Brief Report: Predicting Functional Disability: One-Year Results From the Scottish Early Rheumatoid Arthritis Inception Cohort. Arthritis Rheumatol. 2016;68(7):1596-602. doi: 10.1002/art.39627
16. Katz P. Fatigue in Rheumatoid Arthritis. Curr Rheumatol Rep. 2017;19(5):25. doi: 10.1007/s11926-017-0649-5
17. Curtis JR, Bykerk VP, Aassi M, Schiff M. Adherence and persistence with methotrexate in rheumatoid arthritis: A systematic review. J Rheumatol. 2016;43(11):1997-2009. doi: 10.3899/jrheum.151212
18. Rathbun AM, Harrold LR, Reed GW. Temporal effect of depressive symptoms on the longitudinal evolution of rheumatoid arthritis disease activity. Arthritis Care Res. 2015;67(6):765-75. doi: 10.1002/acr.22515
19. Matcham F, Norton S, Scott DL, et al. Symptoms of depression and anxiety predict treatment response and long-term physical health outcomes in rheumatoid arthritis: secondary analysis of a randomized controlled trial. Rheumatology (Oxford). 2015;(September 2015):269-78. doi: 10.1093/rheumatology/kev306
20. Hider SL, Tanveer W, Brownfield A, et al. Depression in RA patients treated with anti-TNF is common and under-recognized in the rheumatology clinic. Rheumatology. 2009;48(9):1152-4. doi: 10.1093/rheumatology/kep170
21. Michelsen B, Kristianslund EK, Sexton J, et al. Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR-DMARD study. Ann Rheum Dis. 2017;76(11):1906-10. doi: 10.1136/annrheumdis-2017-211284
22. Абрамкин А.А. Влияние коморбидных психических расстройств на эффективность терапии у больных ревматоидным артритом. Научно-практич. ревматология. 2016;54(3):339-45 [Abramkin AA. Impact of comorbid mental disorders on the efficiency of therapy in patients with rheumatoid arthritis. Rheumatology Science and Practice. 2016;54(3):339-45 (In Russ.)]. doi: 10.14412/1995-4484-2016-339-345
23. Matcham F, Ali S, Irving K, et al. Are depression and anxiety associated with disease activity in rheumatoid arthritis? A prospective study. BMC Musculoskelet Dis. 2016;17(1):155. doi: 10.1186/s12891-016-1011-1
24. Schmidt FM, Schröder T, Kirkby KC, et al. Pro- and anti-inflammatory cytokines, but not CRP, are inversely correlated with severity and symptoms of major depression. Psychiatry Res. 2016;239:85-91. doi: 10.1016/j.psychres.2016.02.052
25. Haapakoski R, Mathieu J, Ebmeier KP, et al. Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain Behav Immun. 2015;49:206-15. doi: 10.1016/j.bbi.2015.06.001
26. Duivis HE, Vogelzangs N, Kupper N, et al. Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: Findings from the netherlands study of depression and anxiety (NESDA). Psychoneuroendocrinology. 2013;38(9):1573-85. doi: 10.1016/j.psyneuen.2013.01.002
27. Petersen LE, Baptista TSA, Molina JK, et al. Cognitive impairment in rheumatoid arthritis: role of lymphocyte subsets, cytokines and neurotrophic factors. Clin Rheumatol. January 2018. doi: 10.1007/s10067-018-3990-9
28. Caneo C, Marston L, Bellón JÁ, King M. Examining the relationship between physical illness and depression: Is there a difference between inflammatory and non inflammatory diseases? A cohort study. Gen Hosp Psychiatry. 2016;43:71-7. doi: 10.1016/j.genhosppsych.2016.09.007
29. Ozgonenel L, Cetin E, Tutun S, et al. The relation of serum vascular endothelial growth factor level with disease duration and activity in patients with rheumatoid arthritis. Clin Rheumatol. 2010;29(5):473-7. doi: 10.1007/s10067-009-1343-4
30. Szekanecz Z, Koch AE. VEGF as an activity marker in rheumatoid arthritis. Int J Clin Rheumatol. 2010;5(3):287-9. doi: 10.2217/IJR.10.24
31. Strawbridge R, Young AH, Cleare AJ. Biomarkers for depression: Recent insights, current challenges and future prospects. Neuropsychiatr Dis Treat. 2017;13:1245-62. doi: 10.2147/NDT.S114542
32. Geusens P. The role of RANK ligand/osteoprotegerin in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2012;4(4):225-33. doi: 10.1177/1759720X12438080
33. Cocchi M, Tonello L, Gabrielli F, Pregnolato M. Depression, osteoporosis, serotonin and cell membrane viscosity between biology and philosophical anthropology. Ann Gen Psychiatry. 2011;10:9. doi: 10.1186/1744-859X-10-9
34. Hulejová H, Andrés Cerezo L, Kuklová M, et al. Novel adipokine fibroblast growth factor 21 is increased in rheumatoid arthritis. Physiol Res. 2012;61(5):489-94. doi: 932324 [pii]
35. Sato H, Kazama JJ, Murasawa A, et al. Serum Fibroblast Growth Factor 23 (FGF23) in Patients with Rheumatoid Arthritis. Intern Med. 2016;55(2):121-6. doi: 10.2169/internalmedicine.55.5507
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Авторы
А.А. Абрамкин1, Т.А. Лисицына1, Д.Ю. Вельтищев2,3, О.Ф. Серавина2, О.Б. Ковалевская2, С.И. Глухова1, Е.Л. Насонов1
1 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 Московский научно-исследовательский институт психиатрии – филиал ФГБУ «Национальный медицинский исследовательский центр психиатрии и наркологии им. В.П. Сербского» Минздрава России, Москва, Россия;
3 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
1 Nasonova Research Institute of Rheumatology, Moscow, Russia;
2 Moscow Research Institute of Psychiatry – branch of the Serbskiy National Medical Research Center of Psychiatry and Narcology, Moscow, Russia;
3 Pirogov Russian National Research Medical University, Moscow, Russia
1 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 Московский научно-исследовательский институт психиатрии – филиал ФГБУ «Национальный медицинский исследовательский центр психиатрии и наркологии им. В.П. Сербского» Минздрава России, Москва, Россия;
3 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
________________________________________________
1 Nasonova Research Institute of Rheumatology, Moscow, Russia;
2 Moscow Research Institute of Psychiatry – branch of the Serbskiy National Medical Research Center of Psychiatry and Narcology, Moscow, Russia;
3 Pirogov Russian National Research Medical University, Moscow, Russia
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