Table of Contents  
Year : 2016  |  Volume : 9  |  Issue : 3  |  Page : 294-299  

Depression in systemic sclerosis: Review of the neuro-immunologic link and pharmacological management

1 Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Rheumatology, Sanjay Gandhi Post Graduate Institute, Lucknow, Uttar Pradesh, India

Date of Web Publication17-May-2016

Correspondence Address:
Sujita Kumar Kar
Department of Psychiatry, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-2870.167993

Rights and Permissions

Depression is a common neuropsychiatric condition associated with systemic sclerosis. The association of depression and systemic sclerosis is the result of multiple mechanisms such as autoimmune, significant morbidity due to multi-system involvement, distorted self-image due to disfigurement, chronic disability, and iatrogenic. The prevalence of depression in systemic sclerosis is as high as 65% as found in several clinical studies. Early diagnosis and appropriate intervention of depression in systemic sclerosis through integrated multidisciplinary team approach is more likely to improve the global outcome of illness. Hence, multidisciplinary management approach is highly recommended for the management of depression in systemic sclerosis.

Keywords: Depression, multidisciplinary management approach, systemic sclerosis

How to cite this article:
Somani A, Kar SK, Parida JR. Depression in systemic sclerosis: Review of the neuro-immunologic link and pharmacological management. Med J DY Patil Univ 2016;9:294-9

How to cite this URL:
Somani A, Kar SK, Parida JR. Depression in systemic sclerosis: Review of the neuro-immunologic link and pharmacological management. Med J DY Patil Univ [serial online] 2016 [cited 2022 Dec 2];9:294-9. Available from:

  Introduction Top

Depression is a common psychiatric disorder with an estimated lifetime prevalence of 4.1-4.7% in general population. [1] Throughout the world, depression ranks 4 th for disability-adjusted life-years. [2] Depression affects individuals irrespective of age, gender, and race. Female gender, positive family history of depression, and career uncertainty were some major risk factors of depression in young student population, as found in a study. [3]

Depression takes its own toll of patients who suffer from chronic medical illnesses. While severe and chronic medical illnesses are themselves a risk factor for development of the depressive disorder, depression also plays an important role in course and prognosis of medical conditions. [4] Effective treatment is available for depression in the form of drugs as well as psychotherapy, but depressed medical patients often suffer needlessly. Depression is often missed or remains untreated in this group of patients.

Systemic sclerosis is an autoimmune disorder characterized by aberrant proliferation of fibroblast cells and overexpression of collagen which leads to abnormal fibrosis and affects various parts of human body including skin, blood vessels, gastrointestinal tract, kidneys, lungs, etc. Fibrosis in systemic sclerosis progresses relentlessly, causing outer skin disfigurement as well as inner organ fibrosis. It is a highly disfiguring and disabling condition that results in extensive damage. [5] Neuropsychiatric manifestations of scleroderma have been evaluated by various investigators in different parts of world, and in the majority of studies, depression remains at forefront. [6],[7],[8],[9] The incidence and prevalence of depression in patients with systemic sclerosis are significantly higher than general population. Depression has been found to be an independent determinant of quality of life in patients with systemic sclerosis. [10],[11] Depression affects these patients in more than one ways. It affects patients possibly through autonomic and immunological pathways as well as via cognitive, behavioral, and social processes. It leads to irregularity in adherence to prescribed treatment, increased risk of smoking, and socially isolated behavior. [4],[5],[12],[13],[14]

The importance of understanding and management of psychosocial aspects of systemic sclerosis are increasingly recognized by experts in this field. A consensus agenda about research on this topic has been published in 2010. [14] Various interventions have been proposed, but clear evidences are lacking in absence of any prospective study on depression in patients with systemic sclerosis. [15] It is expected that proper treatment of depression in these patients will help significantly in decreasing their pain and improving their quality of life.

We have searched using the keywords: Systemic sclerosis, scleroderma, depression, immune-biology of depression, and pharmacological management of depression in autoimmune disorders in scientific database systems such as - PubMed/MEDLINE, Google Scholar. All articles focusing on the epidemiology, etiopathogenesis, impact as well as management of depression in systemic sclerosis with emphasis on the immunological linkage of depression and systemic sclerosis were reviewed. This review was planned, considering the close association of depression with systemic sclerosis and one significantly affecting the outcome of other.

  Prevalence of Depression in Patients with Systemic Sclerosis Top

It is a well-known fact that depression is more common in chronic medical conditions as compared to general population. [4] The prevalence of depression has been reported to be 17-27% in patients with cardiovascular disorders, [16] 14-19% in cerebrovascular disorders, [17] 30-50% in Alzheimer's disease, [18] 22-29% in patients of cancer, [19] etc. in comparison to its low prevalence (4.1-4.7%) in general population. [1] A systematic review of studies, that assessed the prevalence of depression in patients with systemic sclerosis was conducted by Thombs et al. in 2007. [5] After evaluating 83 studies on this subject from various standard databases (MEDLINE, PsycINFO, and CINAHL), they found that only 8 studies had followed sound methodology, that is diagnosis of systemic sclerosis using standard criteria and assessment of depression using structured interview or validated questionnaire. Overall, it was found that 36-65% of patients had clinically significant symptoms of depression. [5] The studies could not come up with clear predictors of depression in patients with systemic sclerosis. Among 345 Canadian patients with systemic sclerosis assessed by Jewett et al. in 2013, 1-month, 12-month and lifetime prevalence of major depressive disorder was found to be 3.8%, 10.7%, and 22.9%, respectively. [20] This study was a sub-study of the 15-center Canadian Scleroderma Research Group Registry and used World Mental Health Composite International Diagnostic Interview Version 3.0 (developed by World Health Organization for the World Mental Health Survey) to assess depression. [21] The prevalence of depression in patients of scleroderma was twice that in general Canadian population. [22] Baubet et al. in their study on a French population sample with systemic sclerosis found that current major depressive episode and dysthymia to be 19% and 14%, respectively and current major depressive episode being more common in hospitalized patients. [15],[23] In this study, they found that the lifetime prevalence of major depressive disorder is as high as 56%.

  Causes of Depression in Systemic Sclerosis Top

There are many factors that increase the vulnerability of systemic sclerosis patients to depression. The genesis of depression in these patients is thought to be psycho-neuro-immunological. These patients suffer from high levels of chronic pain, fatigue, body-image dissatisfaction, and significant functional disability. [5] This generates a state of negative emotions which enhance production of pro-inflammatory cytokines, including interleukin-6 (IL-6). [24],[25] IL-6 has been found to be elevated in patients of depression, and its levels are known to decrease after successful treatment with antidepressant medications. [24],[25] The pro-inflammatory cytokines accelerate the process of degradation of neurotransmitter serotonin and its precursor amino acid tryptophan, which may lead to depression. [26] Chronic pain can independently contribute to pathogenesis of depression through elevation of IL-1, IL-6, and tumor necrosis factor-alpha. [27] The influence of pain in genesis of depression in rheumatologic disorders including systemic sclerosis has been reviewed by Goldenberg. [27] Using fibromyalgia as prototype, it has been proposed that several potential mechanisms that is genetic, immunological, neural, and stress-related pathways lead to depression. Chronic fatigue has been reported in around 75% of patients with systemic sclerosis even after controlling for educational level, disease subtype, pain, and sleep quality. [14] Sleep deprivation could be both cause and effect of depression. [28] It has been thought by some that high rates of depressive symptoms among these patients could be due to heavy burden of somatic symptoms. [29] Thombs et al. (2008) evaluated this aspect by assessing differential item functioning [30] and concluded that somatic symptoms possibly led to only 3.6% increase in reported incidence of depression in patients with systemic sclerosis. [30]

Scleroderma often affects visible body parts and causes significant cosmetic deformities, comparable to patients with severe burn injuries. Such deformities have been known to contribute to depression in patients of burn injuries. [31] These patients find difficulty in maintaining routine social contacts and have fear of negative evaluation by others. The distress arising out of dissatisfaction with body image led to poor self-esteem and decreased quality of life. Studies have found that higher levels of body image dissatisfaction, self-rated attractiveness, and fear of negative evaluation were associated with symptoms of anxiety and depression and poorer psychosocial functioning. [14] Impact of body image dissatisfaction has been well studied and has been found to be an important contributor to depression many years after burn injuries. [31] Besides skin tightening, systemic sclerosis causes multiple joint contractures, myositis, and digital ulcerations and in severe cases, gangrene of toes and feet. [32],[33] It can cause pulmonary fibrosis and pulmonary arterial hypertension which contributes to breathlessness and functional incapacitation and are the major causes of mortality. [32],[33] In gastrointestinal system, it causes decreased mouth opening causing decreased food intake, severe gastrointestinal reflux symptoms, dysphagia, chronic diarrhea (bacterial overgrowth syndrome), and anorectal incontinence. [34] Bodukam et al., in their study found that gastrointestinal symptoms intensely associated with depression are gastroesophageal reflux and constipation. [35]

Sexual functions are also compromised due to scleroderma, in both men and women. Contributing factors in women are changes in appearance, skin tightening, vaginal tightness, and dryness of vagina [14] while erectile dysfunction due to vasculopathy in penile tissue is a major factor in men. [14] The erectile dysfunction in these patients responds poorly to sildenafil treatment. Cardiac involvement (arrhythmia, pericardial disease, and myocardial infarction) and renal involvement (scleroderma renal crisis requiring dialysis) are other life-threatening complications of systemic sclerosis. [32] In absence of any definitive medical treatment for systemic sclerosis, all these symptoms negatively affect the quality of life and lead to depression. In a recent review by Leon et al. (2014) involving 48 studies, systemic involvements (gastrointestinal, joint, and vasculo-cutaneous pathology) are found to be frequently associated with negative emotional state, particularly depression. [36]

It was thought that depression in patients with systemic sclerosis is the result of direct involvement of central nervous system (CNS). In a study, Hietaharju et al. found that approximately 16% of patients had neuropsychiatric manifestation due to systemic sclerosis. [37] Launay et al. in a similar study found that 17-65% of patients with systemic sclerosis had features suggestive of depression but also concluded about the rarity of CNS involvement. [34] This study puts forth some insight and raises the possibility of neuropsychiatric manifestations in systemic sclerosis without identifiable CNS abnormalities. [34] It is quite possible that the neuropsychiatric manifestation - Depression in systemic sclerosis is the result of multiple factors discussed above rather than being the outcome of CNS involvement alone. It is, therefore, possible that investigating patients with systemic sclerosis with depression for CNS lesions using computed tomography scan, magnetic resonance imaging, or electroencephalogram might not bring fruitful results.

All the above-mentioned factors are strong generators of negative emotional state and lead to depression. [24] Along with these problems, personality and coping styles of an individual to ongoing stressful situations also contribute to genesis of depression. [24] Positive appraisal of a situation is associated with better outcome of given health situation. Also, the presence of good social support and absence of social isolation are also thought to be protective in stressful life events. [24]

  Impact of Depression on Systemic Sclerosis Top

The impact of depression on chronic medical conditions has been evaluated by various investigators. [4],[14] Depression leads to poor compliance to advised treatment. It has been found that compared to nondepressed patients, odds are three times greater that depressed patients shall turn noncompliant to prescribed medical regimen. [12] The presence of depression increases the incidence of smoking which has its own adverse effects on existing physical illness. [13] It also leads to impairment in cognitive and physical abilities. [4] Health-related quality of life, as expressed by patients, is considered as an important measure of overall experience of the disease. [38] It has been shown by Hyphantis et al. that patients of rheumatologic disorders including systemic sclerosis and other chronic medical conditions have poorer quality of life if they suffer from additional depression and anxiety. [10] Also, these patients are more likely to be socially isolated compared to nondepressed patients. [5] Depression also leads to greater health care utilization and comorbidities in patients with systemic sclerosis. [4],[14] In studies on patients of cardiovascular disorders, cerebrovascular disorders, diabetes mellitus, etc., patients with depression have been noted to have decreased survival compared to nondepressed subjects. [39],[40],[41] Though the impact of depression on mortality of subjects suffering from systemic sclerosis has not been studied adequately, survival and prognosis of depressed patients are expected to be poor.

Depression is an important risk factor for cardiovascular mortality. Systemic sclerosis also affects the cardiovascular system as described above. Depression, in the background of systemic sclerosis possibly, possesses greater risk of cardiovascular mortality and morbidity due to their cumulative effect. Hence, more studies in this domain are warranted. [42],[43]

  Management of Depression in Scleroderma Top

Depression is an important neuropsychiatric disorder commonly associated with scleroderma which adds to the mortality, morbidity, health-care expenditure, and compromises the quality of life. Unfortunately, depression goes undiagnosed or overdiagnosed in the background of systemic sclerosis. The reasons being:

  1. Overlapping clinical symptoms of depression and scleroderma. E.g., loss of appetite, loss of weight, disturbed sleep, and easy fatigability are commonly seen in natural course of progression of systemic sclerosis which may attribute to overdiagnosis or underdiagnosis of depression. [15],[28],[44],[45],[46]
  2. Depression may be over-looked by consideration of the depressive symptoms as a part of normal emotional reaction to the underlying physical illness.
If depression coexists with systemic sclerosis, it should be promptly addressed. Antidepressants are the mainstay of pharmacotherapeutic intervention for depression in systemic sclerosis. Selective serotonin reuptake inhibitors (SSRIs) are safer and found to be effective in the treatment of depression in systemic sclerosis. [42],[47] Patients suffering from systemic sclerosis receive multiple medications with high propensity for drug-drug interaction (corticosteroids, prokinetic drugs, phosphodiesterase inhibitors, etc.). Escitalopram and sertraline may be preferred above other SSRIs as they have relatively lower risk of interaction with other drugs through CYP450 inhibition. [48] Fluoxetine have shown to reduce the frequency of attacks of Raynaud's phenomenon in patients with systemic sclerosis in comparison to nifedipine. [43],[49] Pruritus related to primary biliary cirrhosis in scleroderma respond to sertraline. [50] In presence of cardiovascular and other organ involvement in systemic sclerosis, sertraline is a safe drug. Taken together, SSRI (preferably sertraline) is the preferred drug for treatment of depression in scleroderma. SSRIs are effective in the management of depression mediated by pro-inflammatory cytokines in different immunological disorders. [26] Antidepressants also facilitate the production of anti-inflammatory chemical mediators and decreased production of pro-inflammatory cytokines. [26] Being a multi-systemic disease, there is a need of inter-disciplinary collaboration for its management depression besides various affected vital organs (CNS, Heart, Kidney, Lungs, Skin, Joints, etc.). Addressing the biological, psychological, and social dimensions in the management are needed for better functional outcome and improved quality of life. [36]

Along with pharmacological management, psychotherapies are also likely to help these patients. As of now, specific psychotherapy for management of depression and other symptoms in systemic sclerosis have not been developed, but efforts have been made in this direction in other autoimmune diseases such as rheumatoid arthritis. [51] With advances in technology, now web-based psychological interventions are also being tried which can be a great boon to patients. [52]

  Conclusion Top

Depression is frequently associated with systemic sclerosis but often underdiagnosed. Early diagnosis with proper treatment and counseling is the key to improve outcome. SSRIs are the preferred drug for depression in scleroderma because of its multiple beneficial effects on Raynaud's and pruritus besides depression. Collaboration between rheumatologists and other treating physicians with a psychiatrist is of paramount importance for a better outcome in these chronic morbid patients. Prospective studies are urgently needed to solve many unanswered issues and fill the void in literature.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Baxter AJ, Scott KM, Ferrari AJ, Norman RE, Vos T, Whiteford HA. Challenging the myth of an "epidemic" of common mental disorders: Trends in the global prevalence of anxiety and depression between 1990 and 2010. Depress Anxiety 2014;31:506-16.  Back to cited text no. 1
Insel TR, Charney DS. Research on major depression: Strategies and priorities. JAMA 2003;289:3167-8.  Back to cited text no. 2
Bayati A, Beigi M, Salehi M. Depression prevalence and related factors in Iranian students. Pak J Biol Sci 2009;12:1371-5.  Back to cited text no. 3
Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KR, et al. Mood disorders in the medically ill: Scientific review and recommendations. Biol Psychiatry 2005;58:175-89.  Back to cited text no. 4
Thombs BD, Taillefer SS, Hudson M, Baron M. Depression in patients with systemic sclerosis: A systematic review of the evidence. Arthritis Rheum 2007;57:1089-97.  Back to cited text no. 5
Angelopoulos NV, Drosos AA, Moutsopoulos HM. Psychiatric symptoms associated with scleroderma. Psychother Psychosom 2001;70:145-50.  Back to cited text no. 6
Baubet T, Brunet M, Garcia De La Peña-Lefebvre P, Taïeb O, Moro MR, Guillevin L, et al. Psychiatric manifestations of systemic sclerosis. Ann Med Interne (Paris) 2002;153:237-41.  Back to cited text no. 7
Beretta L, Astori S, Ferrario E, Caronni M, Raimondi M, Scorza R. Determinants of depression in 111 Italian patients with systemic sclerosis. Reumatismo 2006;58:219-25.  Back to cited text no. 8
Waheed A, Hameed K, Khan AM, Syed JA, Mirza AI. The burden of anxiety and depression among patients with chronic rheumatologic disorders at a tertiary care hospital clinic in Karachi, Pakistan. J Pak Med Assoc 2006;56:243-7.  Back to cited text no. 9
Hyphantis T, Tomenson B, Paika V, Almyroudi A, Pappa C, Tsifetaki N, et al. Somatization is associated with physical health-related quality of life independent of anxiety and depression in cancer, glaucoma and rheumatological disorders. Qual Life Res 2009;18:1029-42.  Back to cited text no. 10
Müller H, Rehberger P, Günther C, Schmitt J. Determinants of disability, quality of life and depression in dermatological patients with systemic scleroderma. Br J Dermatol 2012;166:343-53.  Back to cited text no. 11
DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: Meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 2000;160:2101-7.  Back to cited text no. 12
Glassman AH, Helzer JE, Covey LS, Cottler LB, Stetner F, Tipp JE, et al. Smoking, smoking cessation, and major depression. JAMA 1990;264:1546-9.  Back to cited text no. 13
Thombs BD, van Lankveld W, Bassel M, Baron M, Buzza R, Haslam S, et al. Psychological health and well-being in systemic sclerosis: State of the science and consensus research agenda. Arthritis Care Res (Hoboken) 2010;62:1181-9.  Back to cited text no. 14
Malcarne VL, Fox RS, Mills SD, Gholizadeh S. Psychosocial aspects of systemic sclerosis. Curr Opin Rheumatol 2013;25: 707-13.  Back to cited text no. 15
Rudisch B, Nemeroff CB. Epidemiology of comorbid coronary artery disease and depression. Biol Psychiatry 2003;54:227-40.  Back to cited text no. 16
Robinson RG. Poststroke depression: Prevalence, diagnosis, treatment, and disease progression. Biol Psychiatry 2003;54: 376-87.  Back to cited text no. 17
Lee HB, Lyketsos CG. Depression in Alzheimer's disease: Heterogeneity and related issues. Biol Psychiatry 2003;54: 353-62.  Back to cited text no. 18
Raison CL, Miller AH. Depression in cancer: New developments regarding diagnosis and treatment. Biol Psychiatry 2003;54: 283-94.  Back to cited text no. 19
Jewett LR, Razykov I, Hudson M, Baron M, Thombs BD; Canadian Scleroderma Research Group. Prevalence of current, 12-month and lifetime major depressive disorder among patients with systemic sclerosis. Rheumatology (Oxford) 2013;52: 669-75.  Back to cited text no. 20
Kessler RC, Ustün TB. The World Mental Health (WMH) Survey Initiative Version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Int J Methods Psychiatr Res 2004;13:93-121.  Back to cited text no. 21
Patten SB, Wang JL, Williams JV, Currie S, Beck CA, Maxwell CJ, et al. Descriptive epidemiology of major depression in Canada. Can J Psychiatry 2006;51:84-90.  Back to cited text no. 22
Baubet T, Ranque B, Taïeb O, Bérezné A, Bricou O, Mehallel S, et al. Mood and anxiety disorders in systemic sclerosis patients. Presse Med 2011;40:e111-9.  Back to cited text no. 23
Kiecolt-Glaser JK, McGuire L, Robles TF, Glaser R. Emotions, morbidity, and mortality: New perspectives from psychoneuroimmunology. Annu Rev Psychol 2002;53:83-107.  Back to cited text no. 24
Maes M. The cytokine hypothesis of depression: Inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett 2008;29:287-91.  Back to cited text no. 25
Capuron L, Hauser P, Hinze-Selch D, Miller AH, Neveu PJ. Treatment of cytokine-induced depression. Brain Behav Immun 2002;16:575-80.  Back to cited text no. 26
Goldenberg DL. The interface of pain and mood disturbances in the rheumatic diseases. Semin Arthritis Rheum 2010;40:15-31.  Back to cited text no. 27
Frech T, Hays RD, Maranian P, Clements PJ, Furst DE, Khanna D. Prevalence and correlates of sleep disturbance in systemic sclerosis - results from the UCLA scleroderma quality of life study. Rheumatology (Oxford) 2011;50:1280-7.  Back to cited text no. 28
Koenig HG, George LK, Peterson BL, Pieper CF. Depression in medically ill hospitalized older adults: Prevalence, characteristics, and course of symptoms according to six diagnostic schemes. Am J Psychiatry 1997;154:1376-83.  Back to cited text no. 29
Thombs BD, Fuss S, Hudson M, Schieir O, Taillefer SS, Fogel J, et al. High rates of depressive symptoms among patients with systemic sclerosis are not explained by differential reporting of somatic symptoms. Arthritis Rheum 2008;59:431-7.  Back to cited text no. 30
Thombs BD, Haines JM, Bresnick MG, Magyar-Russell G, Fauerbach JA, Spence RJ. Depression in burn reconstruction patients: Symptom prevalence and association with body image dissatisfaction and physical function. Gen Hosp Psychiatry 2007;29:14-20.  Back to cited text no. 31
Generini S, Fiori G, Moggi Pignone A, Matucci Cerinic M, Cagnoni M. Systemic sclerosis. A clinical overview. Adv Exp Med Biol 1999;455:73-83.  Back to cited text no. 32
Moore SC, Desantis ER. Treatment of complications associated with systemic sclerosis. Am J Health Syst Pharm 2008;65: 315-21.  Back to cited text no. 33
Launay D, Baubet T, Cottencin O, Bérezné A, Zéphir H, Morell-Dubois S, et al. Neuropsychiatric manifestations in systemic sclerosis. Presse Med 2010;39:539-47.  Back to cited text no. 34
Bodukam V, Hays RD, Maranian P, Furst DE, Seibold JR, Impens A, et al. Association of gastrointestinal involvement and depressive symptoms in patients with systemic sclerosis. Rheumatology (Oxford) 2011;50:330-4.  Back to cited text no. 35
Leon L, Abasolo L, Redondo M, Perez-Nieto MA, Rodriguez-Rodriguez L, Casado MI, et al. Negative affect in systemic sclerosis. Rheumatol Int 2014;34:597-604.  Back to cited text no. 36
Hietaharju A, Jääskeläinen S, Hietarinta M, Frey H. Central nervous system involvement and psychiatric manifestations in systemic sclerosis (scleroderma): Clinical and neurophysiological evaluation. Acta Neurol Scand 1993;87:382-7.  Back to cited text no. 37
Mura G, Bhat KM, Pisano A, Licci G, Carta M. Psychiatric symptoms and quality of life in systemic sclerosis. Clin Pract Epidemiol Ment Health 2012;8:30-5.  Back to cited text no. 38
Black SA, Markides KS, Ray LA. Depression predicts increased incidence of adverse health outcomes in older Mexican Americans with type 2 diabetes. Diabetes Care 2003;26:2822-8.  Back to cited text no. 39
Frasure-Smith N, Lespérance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA 1993;270:1819-25.  Back to cited text no. 40
House A, Knapp P, Bamford J, Vail A. Mortality at 12 and 24 months after stroke may be associated with depressive symptoms at 1 month. Stroke 2001;32:696-701.  Back to cited text no. 41
Carney RM, Freedland KE, Miller GE, Jaffe AS. Depression as a risk factor for cardiac mortality and morbidity: A review of potential mechanisms. J Psychosom Res 2002;53:897-902.  Back to cited text no. 42
Coleiro B, Marshall SE, Denton CP, Howell K, Blann A, Welsh KI, et al. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 2001;40:1038-43.  Back to cited text no. 43
Ibn Yacoub Y, Amine B, Bensabbah R, Hajjaj-Hassouni N. Assessment of fatigue and its relationships with disease-related parameters in patients with systemic sclerosis. Clin Rheumatol 2012;31:655-60.  Back to cited text no. 44
Milette K, Razykov I, Pope J, Hudson M, Motivala SJ, Baron M, et al. Clinical correlates of sleep problems in systemic sclerosis: The prominent role of pain. Rheumatology (Oxford) 2011;50:921-5.  Back to cited text no. 45
Strickland G, Pauling J, Cavill C, McHugh N. Predictors of health-related quality of life and fatigue in systemic sclerosis: Evaluation of the EuroQol-5D and FACIT-F assessment tools. Clin Rheumatol 2012;31:1215-22.  Back to cited text no. 46
Matsuura E, Ohta A, Kanegae F, Haruda Y, Ushiyama O, Koarada S, et al. Frequency and analysis of factors closely associated with the development of depressive symptoms in patients with scleroderma. J Rheumatol 2003;30:1782-7.  Back to cited text no. 47
Sussman N. Selective serotonin reuptake inhibitors. Kaplan & Sadock's Comprehensive Textbook of Psychiatry. 9 th ed., Vol. 2. Philadelphia: Lippincott Williams & Wilkins; 2009.  Back to cited text no. 48
Garcia-Porrua C, Margarinos CC, Gonzalez-Gay MA. Raynaud's phenomenon and serotonin reuptake inhibitors. J Rheumatol 2004;31:2090.  Back to cited text no. 49
Kumagi T, Heathcote EJ. Primary biliary cirrhosis. Orphanet J Rare Dis 2008;3:1.  Back to cited text no. 50
Evers AW, Kraaimaat FW, van Riel PL, de Jong AJ. Tailored cognitive-behavioral therapy in early rheumatoid arthritis for patients at risk: A randomized controlled trial. Pain 2002;100: 141-53.  Back to cited text no. 51
Nevedal DC, Wang C, Oberleitner L, Schwartz S, Williams AM. Effects of an individually tailored Web-based chronic pain management program on pain severity, psychological health, and functioning. J Med Internet Res 2013;15:e201.  Back to cited text no. 52


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Prevalence of De...
Causes of Depres...
Impact of Depres...
Management of De...

 Article Access Statistics
    PDF Downloaded330    
    Comments [Add]    

Recommend this journal