Efficacy of Olokizumab against Comorbid Depressive Disorder in Patients with Rheumatoid Arthritis: Preliminary Results of the Study.

Interleukin (IL) 6 plays an important role in the pathogenesis of depression comorbid with rheumatoid arthritis (RA), and IL-6 inhibitors used to treat patients with RA may have an antidepressant effect. The objective of the study was to evaluate the effectiveness of Russian iIL-6 olokizumab (OKZ) in reducing symptoms of depression in patients with moderate/high RA activity. To date, 49 RA patients have been included, of which 43 (87.7%) are women, with an average age of 47.8 ± 12.8 years; with a predominant high activity of RA according to DAS28 (CRP) indices (89.8%), SDAI (79.6%) and CDAI (75.5%) and inefficacy of stable 12-week therapy with сDMARDs. In all patients, a psychiatrist, in accordance with ICD-10, diagnosed depression (chronic or recurrent) of varying severity during a semi-structured interview. At week 0, all patients were randomized by the method of sequential numbers in a ratio of 1 : 1 : 1 to one of the three study groups: group 1-cDMARDs + OKZ 64 mg subcutaneously once every 4 weeks (n = 18); group 2-cDMARDs + OKZ 64 mg subcutaneously once every 4 weeks + psychopharmacotherapy (PPT) (n = 26); group 3-cDMARDs + PPT (n = 5). The duration of the study is 24 weeks. The dynamics of depression severity was assessed on the PHQ-9, MADRS scales; anxiety, on HAM-A; experimental psychological projective techniques were also used. After 12 and 24 weeks of therapy, there was a significant decrease in the severity of depression and anxiety in all groups of patients. However, the difference between the final and initial values of all scales was statistically significantly greater (p <0.05) in the groups of patients receiving PPT: cDMARDs + OKZ + PPT (ΔPHQ-9 24-0 = -6.75 ± 3.91; ΔMADRS 24-0 = -22.5 ± 4.83; ΔHAM-A 24-0 = -14.6 ± 5.37) and cDMARDs + PPT (ΔPHQ-9 24-0 = -15.5 ± 3.53; ΔMADRS 24-0 = -25.0 ± 1.41; ΔHAM-A 24-0 = -18.5 ± 3.53), compared with the cDMARDs + OKZ group (ΔPHQ-9 24-0 = -4.00 ± 3.89; ΔMADRS 24-0 = -5.75 ± 8.29; ΔHAM-A 24-0 = -8.50 ± 8.21). According to a semi-structured interview with a psychiatrist and design experimental psychological techniques, the proportion of patients without depression after 24 weeks of therapy was significantly higher in the groups of patients receiving PPT: 90% in the group of cDMARDs + OKZ + PPT and 100%-cDMARDs + PPT, as opposed to 25% in the group of cDMARDs + OKZ. OKZ therapy contributed to the normalization of night sleep but did not lead to a decrease in the frequency and severity of cognitive disorders (CDs). OKZ has an antidepressant effect, leads to a decrease in the frequency of sleep disorders. However, a complete regression of depression symptoms when OKZ is prescribed without PPT is possible only in 25% of RA patients, mainly in the patients with mild depression. A combination of OKZ and PPT is optimal for the complete regression of depression and anxiety and a decrease in the frequency and severity of CDs.

[Anxiety-depressive disorders and stress factors in patients with systemic lupus erythematosus and antiphospholipid syndrome]. / Osobennosti rasstroistv trevozhno-depressivnogo spektra i stressovykh faktorov u bol'nykh sistemnoi krasnoi volchankoi i antifosfolipidnym sindromom.

OBJECTIVE: The aim of this work was to analyze the frequency and, spectrum of mental disorders (MD), and stressful factors, as well as the characteristics of anxiety and depressive spectrum disorders (ADSD) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: The study included 155 patients (37 (23.9%) men and 118 (76.1%) women) aged 18 to 69 years ((M±SD) 37.7±12.3 years), including. 61 (39.3%) patients - with a reliable diagnosis of SLE according to the 2019 EULAR/ACR criteria, 48 (30.9%) patients with - SLE with secondary APS and 46 (29.7%) - with primary APS (PAPS), established according to the international criteria of 2006. RESULTS: The majority of the examined patients were found to hadve MD (current MD in 145 (93.5%) patients). ADSD prevailed in all groups: in 58 (95.1%) patients with SLE, in 42 (87.5%) - with SLE with APS and in, 39 (84.8%) - with APS. Patients with SLE were exposed to stressful events in childhood (predominantly parental deprivation) more often than patients with SLE with APS and PAPS were exposed to stressful events in childhood (93.4% versus 81.2% and 69.6%, respectively; predominantly parental deprivation). ADSD in these patients developed mainly in pre-adolescence, with a tendency towards chronic variants without remission, which leads to a greater vulnerability of the patients in this group to stressful events compared with patients with APS (p=0.05). CONCLUSION: When diagnosing and treating MD in patients with SLE and APS, special attention should be paid to the analysis of the history of stressful eventsstress history of patients, which affects the formation of common predisposing and provoking factors, both MD and RD, aggravating their course and prognosis.

[Cognitive disorders in Behçet's disease]. / Kognitivnye narusheniia pri bolezni Bekhcheta.

AIM: To study the prevalence of cognitive disorders (CD) and clinical/pathogenetic correlations of CD in patients with Behçet's Disease (BD). MATERIAL AND METHODS: One hundred and six BD patients were enrolled in the study. The majority of patients were natives of the North Caucasus (51.9%). Mean age was 33.3±0.98 years, mean illness duration 148.5±10.4 months. All the patients met the criteria of the International Study Group for BD (1990) classification. The disease activity was assessed by scoring system BDCAF. A diagnosis of a mental disorder (MD) was established by the psychiatrist in accordance with the ICD-10 using a semi-structured interview. The Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A), a pathopsychological method 'Pictograms', clinical/psychological methods for assessment of cognitive functions (memory, attention concentration, logic thinking) were administered. Brain MRI was done in 44 (41.5%) BD patients. The study was conducted in the frames of the interdisciplinary program 'Stress factors and mental disorders in immune-mediated inflammatory rheumatic diseases'. RESULTS: CD of mild to moderate severity were diagnosed in 82 (77.4%) and anxiety-depressive disorders in 81 (76.4%) of BD patients. The patients with CD were older compared to patients without cognitive disorders (34.3±1.07 vs 29.0±2.14, p=0.006). Patients with CD were most often (84.1% vs 50.0%, p=0.001) diagnosed with anxiety-depressive disorder (anxiety, chronic/recurrent depression). MADRS scores were higher (16.1±0.74 vs 12.2±1.06, p=0.005) though did not exceed the moderate level. The impact of chronic psychosocial stressors was detected more often in CD patients. MRI results showed that the frequency of chronic multifocal, predominantly subcortical, changes in the white matter was higher in CD patients. CONCLUSION: CD are characteristic of most patients with BD. They are associated with the age, anxiety-depressive disorders, chronic stressors and minor brain multifocal subcortical parenchymal MRI lesions.

Comparative analysis of anxiety-depressive spectrum disorders in patients with rheumatic diseases.

AIM: Research objective - comparative analysis of incidence and structure of anxiety-depressive spectrum disorders (ADD) in patients with various rheumatic diseases (RD). MATERIALS AND METHODS: 613 patients with RD were enrolled in the study: 180 with a reliable diagnosis of systemic lupus erythematosus (SLE), 128 with rheumatoid arthritis (RA), 110 with systemic sclerosis (SSc), 115 with Behcet's disease (BD), 80 with primary Sjögren's syndrome (pSS). Female prevailed in all groups (95% of patients with pSS, 88,2% - SSc, 87,2% - RA, 85,5% of SLE) except BD patients (70% male). The mean age was 42.3±1.54 years and was lower in patients with BD (33.3±0.98 years) and SLE (34.6±0.93 years) compared to patients with SSc (49.9±2.47 years), RA (47.4±0.99 years) and pSS (46.2±2.3 years). The mean RD duration was 130,0±8,65 months and was more at BD - 148,5±10,4 months, pSS - 141,6±8,92 months, RA - 138,4±10,1months, and less at SLE - 134,9±8,8 months and SSc - 87,0±5,04 months. The mean SLE activity index SLEDAI was 9,13±0,63 points (high), RA (DAS28) - 5,26±0,17 points (high), BD (BDCAF) - 3,79±0,2 points (moderate) and SSc by G. Valentini - 1,1±0,20 points (moderate). Glucocorticoids took 100% of patients with pSS, 91,1% - SLE, 90% - SSc, 87% - BD and 67,2% - RA patients; conventional disease modifying anti-rheumatic drugs (cDMARDs) took 90% of patients with SSc, 84% - BD, 79,6% - RA, 68% - pSS, 40,6% - SLE. Biologic DMARDs took 32% of patients with RA, 17,4% - BD, 7,3% - SSc and 7,2% - SLE. Mental disorders were diagnosed by psychiatrist as a result of screening by the hospital anxiety and depression scale (HADS) and in semi-structured interview in accordance with the ICD-10/ DSM-IV. The severity of depression was evaluated by Montgomery-Asberg Depression Rating Scale (MADRS) and anxiety - by Hamilton Anxiety Rating Scale (HAM-A). Projective psychological methods were used for cognitive impairment detection. RESULTS: Screening of depressive disorders (HADS-D≥8) was positive in 180 (29,4%) patients with RD, including 74 (41%) patients with SLE, 38 (35%) - SSc, 29 (23%) - RA, 23 (20%) - BD and 16 (20%) - pSS; anxiety disorders (HADS-A≥8) - in 272 (44,4%) patients, including 66 (52%) patients with RA, 40 (50%) - pSS, 77 (43%) - SLE, 45 (41%) - SSc and 44 (38%) - BD. In accordance with the ICD-10/ DSM-IV depressive disorders have been identified in 389 (63%) patients, including 94 (73%) patients with RA, 71 (64,5%) - SSc, 69 (60%) - BD, 90 (50%) - SLE and 39 (49%) - pSS; anxiety disorders - in 377 (61,5%) patients, including 20 (25%) patients with pSS, 44 (24,5%) - SLE, 29 (23%) - RA, 20 (17%) - BD and 7 (6,4%) - SSc. CONCLUSION: Anxiety-depressive spectrum disorders are typical for most patients with RA, SLE, SSc, pSS and BD. ADDs diagnosis in RD patients with the use of the HADS did not reveal a significant proportion. To obtain objective data on the frequency and structure of ADDs, psychopathological and clinical psychological diagnosis is necessary.

[Risk factors and prevention of recurrent dynamics of depression]. / Faktory riska i profilaktika rekurrentnosti depressii.

The existing literature in the field demonstrates that in the majority of cases depressive disorder has a recurrent course that resulted in negative consequences: an increase in a number of chronic and marked episodes, a higher risk of suicide and stable cognitive deficit. An analysis of predictors promoting the formation of recurrent depressive disorder allows an identification of a constellation of biological, psychological, therapeutic, social factors which should be taken into account in the choice of methods of prevention of the next episode of depression. Currently, the prolonged supporting psychopharmacotherapy, including antidepressant therapy, is a main tactics in the prevention of recurrent dynamics of depressive disorder though its efficacy is understudied.

[Chronic stress and mental disorders in patients with systemic scleroderma: Results of an interdisciplinary study]. / Khronicheskie stress i psikhicheskie rasstroistva u bol'nykh sistemnoi sklerodermiei: rezul'taty mezhdistsiplinarnogo issledovaniia.

AIM: To analyze of the prevalence of stressful factors and mental disorders (MDs), as well as their clinical psychopathological and clinical psychological characteristics to improve the comprehensive diagnosis and treatment of systemic scleroderma (SSD). SUBJECTS AND METHODS: Examinations were performed in 110 patients (predominantly women (n=97 (88.2%); mean age, 49.9±2.47 years) with a documented diagnosis of SSD (its mean duration, 7.25±0.42 years). 62 (56.4%) patients had limited SSD, 36 (32.7%) had diffuse SSD, and 12 (10.9%) had overlap syndrome. The disease was rapidly and slowly progressive in 33 (30%) and 77 (70%) patients, respectively. Oral glucocorticosteroids were used in 99 (90%) patients included in the study, cytotoxic drugs in 66 (60%), plaquenil in 33 (30%); 8 (7%) patients were treated with the biological agent rituximab. All the patients were examined by a psychologist and a psychiatrist. The psychopathological diagnosis of MD was made during a semistructured interview in accordance with the ICD-10 criteria. The Montgomery-Asberg depression and Hamilton anxiety rating scales were used to evaluate the severity of depression and anxiety, respectively. All patients underwent a clinical and psychological examination, including tests assessing memory, attention, and logical thinking, as well as projective techniques. RESULTS: MDs were detected in 91 (83%) patients with SSD. There was a preponderance of depressive disorders in 74 (67.3%) patients: chronic (dysthymia in 33 (30%) patients)) and recurrent (recurrent depressive disorder in 34 (31%)) depressions. Cognitive impairment (CI) of varying severities was diagnosed in 100% of the patients. Schizotypal personality disorder was stated in 44 (40%) patients. 90% of patients were found to have chronic psychic traumas mainly as parental deprivation in childhood (in children less than 11 years of age). 76.7% of the SSD cases developed recurrent episodes of depression in the presence of long-term MD or had a history of the episodes. There was no relationship of MD to gender, age, duration of SSD and its individual clinical manifestations. The nature of SSD treatment did not affect the frequency and spectrum of MD. CONCLUSION: MDs, predominantly chronic and recurrent depression, and CI are characteristic of most SSD patients. Multiple chronic stressful factors, both previous SSD and those over time, have commonly an impact on the mental health of patients with SSD.

[Psychotraumatic factors and anxiety-depressive spectrum disorders in Behcet's disease: the interdisciplinary study].

OBJECTIVE: To determine the frequency and variants of anxiety-depressive spectrum disorders (ADSD) in Behcet's disease (BD) and the effects of psychotraumatic factors, personality and clinical symptoms of the rheumatic disease. MATERIAL AND METHODS: Authors examined 60 patients with confirmed BD diagnosis made according to ISGBD criteria. The degree of BD activity was assessed using BDCAF index. The disease severity was ranged according to Ch. Zouboulis classification. All patients underwent complex rheumatologic, psychopathologic and psychological examinations. Childhood psychological trauma and stress factors before BD were analyzed. RESULTS: Most of the patients (86.7%) were diagnosed with a wide spectrum of ICD-10 ADSD: dysthymia (33.3%), recurrent depressive disorders (28.3%) mild or moderate depressive episode (11.7%), generalized anxiety disorder (6.7%), adjustment disorder with anxiety-depressive syndrome (6.7%). Mental disorders were not identified only in 13.3% of patients. The frequency of cognitive impairment (CI) was 88.3%, including 42.7% with mild CI. BD activity, ADSD severity and as well as factors not-related to disease contributed to CI development and severity. Psychological trauma during childhood and adolescence were found in 35 (58.3%) of patients. BD with early onset was recorded more often in the group with psychological trauma at the age <7 years compared to the group without psychological trauma. Treatment adherence was noted in most patients (70%) with BD and ADSD. CONCLUSION: The results confirm the need of timely diagnosis and adequate treatment of ADSD in patients with BD to improve treatment adherence and prognosis of disease.

[The magnitude of fatigue and its association with depression, pain, and inflammatory activity in rheumatoid arthritis].

AIM: To analyze the rate of clinically significant fatigue and to search for its predictors in patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: The investigation included 95 patients with a valid RA diagnosis. The majority of the patients were women (87.4%); mean age was 46.7 +/- 1.2 years; mean disease duration was 135.5 +/- 11.6 months. The authors evaluated RA activity by the Disease Activity Score (DAS28), magnitude of fatigue by the Fatigue Severity Scale (FSS), that of pain by the Brief Pain Inventory, and functional status and quality of life by the Health Assessment Questionnaire and EQ-5D. A psychiatrist diagnosed mental disorders in accordance with ICD-10 and using the psychiatric and psychological scales and procedures. RESULTS: 80% of the patients felt clinically significant fatigue (FSS scores of > or = 4). Multivariate analysis yielded a prognostic model that made it possible to state that clinically significant fatigue was primarily associated with the magnitude of depression by the Hospital Anxiety and Depression Scale, the presence of a depressive episode, the duration of anxiety and depressive spectrum, the magnitude of pain (Ritchie index), DAS28, and the presence of osteoporosis. CONCLUSION: The presence and magnitude of depression along with the magnitude of pain are an important factor that influences the formation of fatigue in RA, which gives rise to evident functional failure and a low quality of life. Combination therapy for RA may be effective when mental disorders, mainly the anxiety and depressive spectrum, are timely diagnosed.