Current Psychiatry Reports

, Volume 6, Issue 3, pp 193–201 | Cite as

Impact of medical comorbid disease on antidepressant treatment of major depressive disorder

  • Dan V. Iosifescu
  • Bettina Bankier
  • Maurizio Fava


A major factor in evaluating and treating depression is the presence of comorbid medical problems. In this paper, the authors will first evaluate studies showing that medical illness is a risk factor for depression. The authors will review a series of randomized, controlled studies of antidepressant treatment in subjects with major depressive disorder (MDD) and comorbid medical illnesses (myocardial infarction, stroke, diabetes, cancer, and rheumatoid arthritis). Most of these studies report an advantage for an active antidepressant over placebo in improvement of depressive symptoms. The authors also will review a series of studies in which the outcome of antidepressant treatment is compared between subjects with MDD with and without comorbid medical illness. In these studies, subjects with medical illness tend to have lower improvement of depressive symptoms and higher rates of depressive relapse with antidepressant treatment compared with MDD subjects with no medical comorbidity. In addition, the authors will review hypotheses on the mechanism of the interaction between medical illness and clinical response in MDD. The paper will conclude that medical comorbidity is a predictor of treatment resistance in MDD.


Fluoxetine Paroxetine Major Depressive Disorder Antidepressant Treatment Nortriptyline 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Krishnan KR, Delong M, Kraemer H, et al.: Comorbidity of depression with other medical diseases in the elderly. Biol Psychiatry 2002, 52:559–588. A major review of the comorbidity of depression and medical illnesses that opens with an important general discussion of the concept of comorbidity.PubMedCrossRefGoogle Scholar
  2. 2.
    Frasure-Smith N, Lesperance F, Talajic M: Depression following myocardial infarction: impact on 6-month survival. JAMA 1993, 270:1819–1825.PubMedCrossRefGoogle Scholar
  3. 3.
    Frasure-Smith N, Lesperance F, Talajic M: Depression and 18-month prognosis after myocardial infarction. Circulation 1995, 91:999–1005.PubMedGoogle Scholar
  4. 4.
    Bush DE, Zigelstein RC, Tayback M, et al.: Even minimal symptoms of depression increase mortality risk after acute myocardial infarction. Am J Cardiol 2001, 88:337–341.PubMedCrossRefGoogle Scholar
  5. 5.
    Kauhanen M, Korpelainen JT, Hiltunen P, et al.: Post-stroke depression correlates with cognitive impairment and neurological deficits. Stroke 1999, 30:1875–1880.PubMedGoogle Scholar
  6. 6.
    Jorge RE, Robinson RG, Arndt S, Starkstein S: Mortality and post-stroke depression: a placebo-controlled trial of antidepressants. Am J Psychiatry 2003, 160:1823–1829.PubMedCrossRefGoogle Scholar
  7. 7.
    de Groot M, Anderson R, Freedland KE, et al.: Association of depression and diabetes complications: a meta-analysis. Psychosom Med 2001, 63:619–630.PubMedGoogle Scholar
  8. 8.
    Spiegel D, Giese-Davis J: Depression and cancer: mechanisms and disease progression. Biol Psychiatry 2003, 54:269–282.PubMedCrossRefGoogle Scholar
  9. 9.
    Ganzini L, Smith DM, Fenn DS, Lee MA: Depression and mortality in medically ill older adults. J Am Geriatr Soc 1997, 45:307–312.PubMedGoogle Scholar
  10. 10.
    Covinsky KE, Kahana E, Chin MH, et al.: Depressive symptoms and 3-year mortality in older hospitalized medical patients. Ann Intern Med 1999, 130:563–569.PubMedGoogle Scholar
  11. 11.
    Gillespie L: The clinical differentiation of types of depression. Guys Hosp Rep 1929, 79:231–233.Google Scholar
  12. 12.
    Lewis A: Melancholia: a clinical survey of depressive states. J Ment Sci 1984, 80:277–378.Google Scholar
  13. 13.
    Woodruff RA, Jr., Murphy GE, Herjanic M: The natural history of affective disorders, I: symptoms of 72 patients at the time of index hospital admission. J Psychiatr Res 1967, 5:255–263.PubMedCrossRefGoogle Scholar
  14. 14.
    Feighner JP, Robins E, Guze SB, et al.: Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 1972, 26:57–63.PubMedGoogle Scholar
  15. 15.
    Klerman GL: Depression in the medically ill. Psychiatr Clin North Am 1981, 4:301–317.PubMedGoogle Scholar
  16. 16.
    Andreasen NC, Winokur G: Secondary depression: familial, clinical, and research perspectives. Am J Psychiatry 1979, 136:62–66.PubMedGoogle Scholar
  17. 17.
    Akiskal HS, Rosenthal RH, Rosenthal TL, et al.: Differentiation of primary affective illness from situational, symptomatic, and secondary depressions. Arch Gen Psychiatry 1979, 36:635–643.PubMedGoogle Scholar
  18. 18.
    Hirschfeld RM, Klerman GL, Andreasen NC, et al.: Situational major depressive disorder. Arch Gen Psychiatry 1985, 42:1109–1114.PubMedGoogle Scholar
  19. 19.
    American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, edn 4 (Text Revision). Washington, DC: American Psychiatric Publishing, Inc.; 2000.CrossRefGoogle Scholar
  20. 20.
    Schleifer SJ, Macari-Hinson MM, Coyle DA, et al.: The nature and course of depression following myocardial infarction. Arch Intern Med 1989, 149:1785–1789.PubMedCrossRefGoogle Scholar
  21. 21.
    Ziegelstein RC, Fauerbach JA, Stevens SS, et al.: Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch Intern Med 2000, 160:1818–1823.PubMedCrossRefGoogle Scholar
  22. 22.
    Lesperance F, Frasure-Smith N, Talajic M: Major depression before and after myocardial infarction: its nature and consequences. Psychosom Med 1996, 58:99–110.PubMedGoogle Scholar
  23. 23.
    Aben I, Verhey F, Strik J, et al.: A comparative study into the one-year cumulative incidence of depression after stroke and myocardial infarction. J Neurol Neurosurg Psychiatry 2003, 74:581–585.PubMedCrossRefGoogle Scholar
  24. 24.
    Carney RM, Rich MW, Tevelde A, et al.: Major depressive disorder in coronary artery disease. Am J Cardiol 1987, 60:1273–1275.PubMedCrossRefGoogle Scholar
  25. 25.
    Dew MA, Roth LH, Schulberg HC, et al.: Prevalence and predictors of depression and anxiety-related disorders during the year after heart transplantation. Gen Hosp Psychiatry 1996, 18(suppl):48S-61S.PubMedCrossRefGoogle Scholar
  26. 26.
    Jiang W, Alexander J, Christopher E, et al.: Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure. Arch Intern Med 2001, 161:1849–1856.PubMedCrossRefGoogle Scholar
  27. 27.
    Turvey CL, Schultz K, Arndt S, et al.: Prevalence and correlates of depressive symptoms in a community sample of people suffering from heart failure. J Am Geriatr Soc 2002, 50:2003–2008.PubMedCrossRefGoogle Scholar
  28. 28.
    Robinson RG, Starr LB, Price TR: A two-year longitudinal study of mood disorders following stroke: prevalence and duration at six months follow-up. Br J Psychiatry 1984, 144:256–262.PubMedCrossRefGoogle Scholar
  29. 29.
    Astrom M, Adolfsson R, Asplund K: Major depression in stroke patients: a 3-year longitudinal study. Stroke 1993, 24:976–982.PubMedGoogle Scholar
  30. 30.
    Cassidy E, O’Connor R, O’Keane V: Prevalence of post-stroke depression in an Irish sample and its relationship with disability and outcome following inpatient rehabilitation. Disabil Rehabil 2004, 26:71–77.PubMedCrossRefGoogle Scholar
  31. 31.
    Jonas BS, Franks P, Ingram DD: Are symptoms of anxiety and depression risk factors for hypertension? Longitudinal evidence from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. Arch Fam Med 1997, 6:43–49.PubMedCrossRefGoogle Scholar
  32. 32.
    Davidson K, Jonas BS, Dixon KE, Markovitz JH: Do depression symptoms predict early hypertension incidence in young adults in the CARDIA study? Coronary artery risk development in young adults. Arch Intern Med 2000, 160:1495–1500.PubMedCrossRefGoogle Scholar
  33. 33.
    Rabkin JG, Charles E, Kass F: Hypertension and DSM-III depression in psychiatric outpatients. Am J Psychiatry 1983, 140:1072–1074.PubMedGoogle Scholar
  34. 34.
    Bosworth HB, Bartash RM, Olsen MK, Steffens DC: The association of psychosocial factors and depression with hypertension among older adults. Int J Geriatr Psychiatry 2003, 18:1142–1148.PubMedCrossRefGoogle Scholar
  35. 35.
    Jess P, Eldrup J: The personality patterns in patients with duodenal ulcer and ulcer-like dyspepsia and their relationship to the course of the diseases. Hvidovre Ulcer Project Group. J Intern Med 1994, 235:589–594.PubMedCrossRefGoogle Scholar
  36. 36.
    Levenstein S, Kaplan GA, Smith MW: Psychological predictors of peptic ulcer incidence in the Alameda County Study. J Clin Gastroenterol 1997, 24:140–146.PubMedCrossRefGoogle Scholar
  37. 37.
    Gavard JA, Lustman PJ, Clouse RE: Prevalence of depression in adults with diabetes: an epidemiological evaluation. Diabetes Care 1993, 16:1167–1178.PubMedCrossRefGoogle Scholar
  38. 38.
    Anderson RJ, Freedland KE, Clouse RE, Lustman PJ: The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001, 24:1069–1078.PubMedCrossRefGoogle Scholar
  39. 39.
    McDaniel JS, Musselman DL, Porter MR, et al.: Depression in patients with cancer: diagnosis, biology, and treatment. Arch Gen Psychiatry 1995, 52:89–99.PubMedGoogle Scholar
  40. 40.
    Koenig HG, Meador KG, Cohen HJ, Blazer DG: Depression in elderly hospitalized patients with medical illness. Arch Intern Med 1988, 148:1929–1936.PubMedCrossRefGoogle Scholar
  41. 41.
    Koenig HG, Meador KG, Shelp F, et al.: Major depressive disorder in hospitalized medically ill patients: an examination of young and elderly male veterans. J Am Geriatr Soc 1991, 39:881–890.PubMedGoogle Scholar
  42. 42.
    Wells KB, Rogers W, Burnam A, et al.: How the medical comorbidity of depressed patients differs across health care settings: results from the Medical Outcomes Study. Am J Psychiatry 1991, 148:1688–1696.PubMedGoogle Scholar
  43. 43.
    Patten SB: Long-term medical conditions and major depression in the Canadian population. Can J Psychiatry 1999, 44:151–157.PubMedGoogle Scholar
  44. 44.
    Watkins LL, Schneiderman N, Blumenthal JA, et al.: Cognitive and somatic symptoms of depression are associated with medical comorbidity in patients after acute myocardial infarction. Am Heart J 2003, 146:48–54. In this study, patients with acute MI and depressive disorders had significantly higher levels of medical comorbidity compared with nondepressed, socially isolated patients after MI.PubMedCrossRefGoogle Scholar
  45. 45.
    Nelson JC, Kennedy JS, Pollock BG, et al.: Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease. Am J Psychiatry 1999, 156:1024–1028.PubMedGoogle Scholar
  46. 46.
    Strik JJ, Honig A, Lousberg R, et al.: Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial. Psychosom Med 2000, 62:783–789.PubMedGoogle Scholar
  47. 47.
    Glassman AH, O’Connor CM, Califf RM, et al.: Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002, 288:701–709. This study reported that treatment with sertraline in post-MI and unstable angina patients was very safe, with a decreased incidence of severe cardiovascular adverse events in the sertraline group (not statistically significant). Sertraline was more efficacious than placebo in the treatment of depressive symptoms for post-MI subjects with recurrent depression.PubMedCrossRefGoogle Scholar
  48. 48.
    Andersen G, Vestergaard K, Lauritzen L: Effective treatment of post-stroke depression with the selective serotonin reuptake inhibitor citalopram. Stroke 1994, 25:1099–1104.PubMedGoogle Scholar
  49. 49.
    Robinson RG, Schultz SK, Castillo C, et al.: Nortriptyline versus fluoxetine in the treatment of depression and in shortterm recovery after stroke: a placebo-controlled, doubleblind study. Am J Psychiatry 2000, 157:351–359. In this study, nortriptyline was superior to fluoxetine or placebo in the treatment of poststroke depression.PubMedCrossRefGoogle Scholar
  50. 50.
    Wiart L, Petit H, Joseph PA, et al.: Fluoxetine in early poststroke depression: a double-blind placebo-controlled study. Stroke 2000, 31:1829–1832.PubMedGoogle Scholar
  51. 51.
    Fruehwald S, Gatterbauer E, Rehak P, Baumhackl U: Early fluoxetine treatment of post-stroke depression: a three-month double-blind placebo-controlled study with an open-label longterm follow up. J Neurol 2003, 250:347–351.PubMedCrossRefGoogle Scholar
  52. 52.
    Lustman PJ, Griffith LS, Clouse RE, et al.: Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial. Psychosom Med 1997, 59:241–250.PubMedGoogle Scholar
  53. 53.
    Lustman PJ, Freedland KE, Griffith LS, Clouse RE: Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial. Diabetes Care 2000, 23:618–623. This study reports fluoxetine was efficacious in treating depression in diabetes patients. Fluoxetine also showed a trend toward improved glycemic control compared with placebo.PubMedCrossRefGoogle Scholar
  54. 54.
    Razavi D, Allilaire JF, Smith M, et al.: The effect of fluoxetine on anxiety and depression symptoms in cancer patients. Acta Psychiatr Scand 1996, 94:205–210.PubMedGoogle Scholar
  55. 55.
    van Heeringen K, Zivkov M: Pharmacological treatment of depression in cancer patients: a placebo-controlled study of mianserin. Br J Psychiatry 1996, 169:440–443.PubMedCrossRefGoogle Scholar
  56. 56.
    Holland JC, Romano SJ, Heiligenstein JH, et al.: A controlled trial of fluoxetine and desipramine in depressed women with advanced cancer. Psychooncology 1998, 7:291–300.PubMedCrossRefGoogle Scholar
  57. 57.
    Pezzella G, Moslinger-Gehmayr R, Contu A: Treatment of depression in patients with breast cancer: a comparison between paroxetine and amitriptyline. Breast Cancer Res Treat 2001, 70:1–10.PubMedCrossRefGoogle Scholar
  58. 58.
    Ash G, Dickens CM, Creed FH, et al.: The effects of dothiepin on subjects with rheumatoid arthritis and depression. Rheumatology (Oxford) 1999, 38:959–967.CrossRefGoogle Scholar
  59. 59.
    Bird H, Broggini M: Paroxetine versus amitriptyline for treatment of depression associated with rheumatoid arthritis: a randomized, double blind, parallel group study. J Rheumatol 2000, 27:2791–2797.PubMedGoogle Scholar
  60. 60.
    Parker JC, Smarr KL, Slaughter JR, et al.: Management of depression in rheumatoid arthritis: a combined pharmacologic and cognitive-behavioral approach. Arthritis Rheum 2003, 49:766–777.PubMedCrossRefGoogle Scholar
  61. 61.
    Popkin MK, Callies AL, Mackenzie TB: The outcome of antidepressant use in the medically ill. Arch Gen Psychiatry 1985, 42:1160–1163.PubMedGoogle Scholar
  62. 62.
    Koenig HG, Goli V, Shelp F, et al.: Antidepressant use in elderly medical inpatients: lessons from an attempted clinical trial. J Gen Intern Med 1989, 4:498–505.PubMedCrossRefGoogle Scholar
  63. 63.
    Keitner GI, Ryan CE, Miller IW, et al.: 12-month outcome of patients with major depression and comorbid psychiatric or medical illness (compound depression). Am J Psychiatry 1991, 148:345–350.PubMedGoogle Scholar
  64. 64.
    Small GW, Birkett M, Meyers BS, et al.: Impact of physical illness on quality of life and antidepressant response in geriatric major depression: Fluoxetine Collaborative Study Group. J Am Geriatr Soc 1996, 44:1220–1225.PubMedGoogle Scholar
  65. 65.
    Evans M, Hammond M, Wilson K, et al.: Placebo-controlled treatment trial of depression in elderly physically ill patients. Int J Geriatr Psychiatry 1997, 12:817–824.PubMedCrossRefGoogle Scholar
  66. 66.
    Evans M, Hammond M, Wilson K, et al.: Treatment of depression in the elderly: effect of physical illness on response. Int J Geriatr Psychiatry 1997, 12:1189–1194.PubMedCrossRefGoogle Scholar
  67. 67.
    Alexopoulos GS, Meyers BS, Robert YC, et al.: Executive dysfunction and long-term outcomes of geriatric depression. Arch Gen Psychiatry 2000, 57:285–290.PubMedCrossRefGoogle Scholar
  68. 68.
    Koike AK, Unutzer J, Wells KB: Improving the care for depression in patients with comorbid medical illness. Am J Psychiatry 2002, 159:1738–1745.PubMedCrossRefGoogle Scholar
  69. 69.
    Oslin DW, Datto CJ, Kallan MJ, et al.: Association between medical comorbidity and treatment outcomes in late-life depression. J Am Geriatr Soc 2002, 50:823–828.PubMedCrossRefGoogle Scholar
  70. 70.
    Papakostas GI, Petersen T, Iosifescu DV, et al.: Axis III disorders in treatment-resistant major depressive disorder. Psychiatry Res 2003, 118:183–188.PubMedCrossRefGoogle Scholar
  71. 71.
    Iosifescu DV, Nierenberg AA, Alpert JE, et al.: The impact of medical comorbidity on acute treatment in major depressive disorder. Am J Psychiatry 2003, 160:2122–2127. This study reports that the total burden of medical illness and the number of organ systems involved by medical illness have a significant negative impact on the outcome of antidepressant treatment in major depressive disorder. No single medical illness was responsible for this effect, which was statistically significant only when the cumulated burden of all comorbid medical diseases was taken into consideration.PubMedCrossRefGoogle Scholar
  72. 72.
    Perlis RH, Iosifescu DV, Alpert JE, et al.: Medical comorbidity does not moderate response to augmentation or dose increase among depressed outpatients resistant to fluoxetine 20 mg/day. Psychosomatics 2004, in press.Google Scholar
  73. 73.
    Iosifescu DV, Nierenberg AA, Alpert JE, et al.: Comorbid medical illness and relapse of major depressive disorder in the continuation phase of treatment. Psychosomatics 2004, in press. This study reports that the total burden and severity of comorbid medical illness significantly predicted the relapse of MDD during continuation therapy with fluoxetine.Google Scholar
  74. 74.
    Miller MD, Paradis CF, Houck PR, et al.: Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 1992, 41:237–248.PubMedCrossRefGoogle Scholar
  75. 75.
    Ciechanowski PS, Katon WJ, Russo JE: Depression and diabetes: impact of depressive symptoms on adherence, function, and costs. Arch Intern Med 2000, 160:3278–3285.PubMedCrossRefGoogle Scholar
  76. 76.
    DeVane CL: Metabolism and pharmacokinetics of selective serotonin reuptake inhibitors. Cell Mol Neurobiol 1999, 19:443–466.CrossRefGoogle Scholar
  77. 77.
    Brown ES, Varghese FP, McEwen BS: Association of depression with medical illness: does cortisol play a role? Biol Psychiatry 2004, 55:1–9. Important review of the role of hypercortisolemia and HPA axis dysregulation in the pathology of MDD and a series of medical illnesses. The authors propose hypercortisolemia and HPA axis dysregulation as a possible link between the biology of depression and medical illness.PubMedCrossRefGoogle Scholar
  78. 78.
    Arana GW, Baldessarini JR, Ornsteen M: The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Arch Gen Psychiatry 1985, 42:1193–1204.PubMedGoogle Scholar
  79. 79.
    Lenox RH, Teyser JM, Rothschild B, et al.: Failure to normalize the dexamethasone suppression test: association with length of illness. Biol Psychiatry 1985, 20:329–352.CrossRefGoogle Scholar
  80. 80.
    Targum SD: Persistent neuroendocrine dysregulation in major depressive disorder: a marker for early relapse. Biol Psychiatry 1984, 19:305–318.PubMedCrossRefGoogle Scholar
  81. 81.
    Young EA, Lopez JF, Murphy-Weinberg V, et al.: Hormonal evidence for altered responsiveness to social stress in major depression. Neuropsychopharmacology 2000, 23:411–418.PubMedCrossRefGoogle Scholar
  82. 82.
    McEwen BS: Effects of adverse experiences for brain structure and function. Biol Psychiatry 2000, 48:721–731.PubMedCrossRefGoogle Scholar
  83. 83.
    Sheline YI, Wang PW, Gado MH, et al.: Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A 1996, 93:3908–3913.PubMedCrossRefGoogle Scholar
  84. 84.
    Steffens DC, Byrum CE, McQuoid DR, et al.: Hippocampal volume in geriatric depression. Biol Psychiatry 2000, 48:301–309.PubMedCrossRefGoogle Scholar
  85. 85.
    Krakoff LR: Glucocorticoid excess syndromes causing hypertension. Cardiol Clin 1988, 6:537–545.PubMedGoogle Scholar
  86. 86.
    Lechin F, van der Dijs B, Rada I, et al.: Plasma neurotransmitters and cortisol in duodenal ulcer patients: role of stress. Dig Dis Sci 1990, 35:1313–1319.PubMedCrossRefGoogle Scholar
  87. 87.
    Roy MS, Roy A, Brown S: Increased urinary-free cortisol outputs in diabetic patients. J Diabetes Complications 1998, 12:24–27.PubMedCrossRefGoogle Scholar
  88. 88.
    Hricik DE, Mayes JT, Schulak JA: Independent effects of cyclosporine and prednisone on post-transplant hypercholesterolemia. Am J Kidney Dis 1991, 18:353–358.PubMedGoogle Scholar
  89. 89.
    Gottsater A, Forsblad J, Matzsch T, et al.: Interleukin-1 receptor antagonist is detectable in human carotid artery plaques and is related to triglyceride levels and Chlamydia pneumoniae IgA antibodies. J Intern Med 2002, 251:61–68.PubMedCrossRefGoogle Scholar
  90. 90.
    Stenvinkel P, Heimburger O, Jogestrand T: Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in dialysis patients: association with Chlamydia pneumoniae seropositivity. Am J Kidney Dis 2002, 39:274–282.PubMedGoogle Scholar
  91. 91.
    Cottone S, Mule G, Amato F, et al.: Amplified biochemical activation of endothelial function in hypertension associated with moderate to severe renal failure. J Nephrol 2002, 15:643–648.PubMedGoogle Scholar
  92. 92.
    van der Meer IM, de Maat MP, Bots ML, et al.: Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study. Arterioscler Thromb Vasc Biol 2002, 22:838–842.PubMedCrossRefGoogle Scholar
  93. 93.
    Reid PT, Sallenave JM: Cytokines in the pathogenesis of chronic obstructive pulmonary disease. Curr Pharm Des 2003, 9:25–38.PubMedCrossRefGoogle Scholar
  94. 94.
    Woodman RJ, Watts GF, Puddey IB, et al.: Leukocyte count and vascular function in type 2 diabetic subjects with treated hypertension. Atherosclerosis 2002, 163:175–181.PubMedCrossRefGoogle Scholar
  95. 95.
    Yirmiya R, Pollak Y, Morag M, et al.: Illness, cytokines, and depression. Ann N Y Acad Sci 2000, 917:478–487.PubMedCrossRefGoogle Scholar
  96. 96.
    Meyers CA: Mood and cognitive disorders in cancer patients receiving cytokine therapy. In Cytokines, Stress and Depression. Edited by Dantzer R, Wollman EE, Yirmiya R. New York: Kluwer Academic/Plenum Publishers; 1999:75–81.Google Scholar
  97. 97.
    Dantzer R, Wollman E, Vitkovic L, Yirmiya R: Cytokines and depression: fortuitous or causative association. Mol Psychiatry 1999, 4:328–332.PubMedCrossRefGoogle Scholar
  98. 98.
    Dantzer R: Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 2001, 15:7–24.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2004

Authors and Affiliations

  • Dan V. Iosifescu
    • 1
  • Bettina Bankier
  • Maurizio Fava
  1. 1.Massachusetts General HospitalBostonUSA

Personalised recommendations