Psychiatry Below the Neck

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The slides that accompanied a lecture on the physical complications of depression, stress and anxiety.

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Psychiatry Below the Neck

  1. 1. Psychiatry Below the Neck: The Physical Consequences of Depression, Stress and Anxiety Richard G Petty MD, MSc, MRCP(UK), MRCPsych, Promedica Research Center, Georgia State University College of Health Sciences, Loganville, Georgia, USA rpettyus@aol.com RichardGPettyMD.com Sunday, July 26, 2009
  2. 2. Disclosure Richard G. Petty, MD, MSc, MRCP(UK), MRCPsych  Consultant • AstraZeneca; Eli Lilly and Company; Janssen Pharmaceuticals  Speaker’s Bureau • Abbott Pharmaceuticals, Astra Zeneca; Janssen Pharmaceuticals  Grant Support • British Diabetic Association; Bristol Meyers Squibb; British Heart Foundation; Du Pont Merck, Inc.; Eli Lilly and Company; Janssen; Medical Research Council (UK); National Institute of Mental Health; Pfizer Sunday, July 26, 2009
  3. 3. Objectives  1. Attendees will be able to list the main cardiovascular, endocrine, metabolic, immunological and oncological associations of depression, stress and anxiety  2. Participants will be able to describe the impact of depression, stress and anxiety on pre-existing physical illnesses  3. Attendees will be able to screen for the physical problems associated with depression, stress and anxiety Sunday, July 26, 2009
  4. 4. There Is a Serious Lack of Physical Well-being in Individuals With Major Mental Illness: Not Only Schizophrenia, But Also Bipolar Disorder and Major Depressive Disorder Sunday, July 26, 2009
  5. 5. There Is a Serious Lack of Physical Well-being in Individuals With Major Mental Illness: Not Only Schizophrenia, But Also Bipolar Disorder and Major Depressive Disorder  Mortality rates: people die on average 10-20 years earlier than the general population1-3 Sunday, July 26, 2009
  6. 6. There Is a Serious Lack of Physical Well-being in Individuals With Major Mental Illness: Not Only Schizophrenia, But Also Bipolar Disorder and Major Depressive Disorder  Mortality rates: people die on average 10-20 years earlier than the general population1-3  In part because of suicide, but also:  Cardiovascular diseases  Coronary artery disease 4  Arrhythmias  Diabetes mellitus - Type II5  Obesity6  Some forms of cancer  Respiratory illness  Substance abuse7 1. Harris, E.C. and Barraclough, B. Br J Psychiatry 1998; 173: 11-53 2. Newman and Bland Can J Psychiatry 1991; 36: 239-245 3. Tabbane, K., R. Joober, et al. 1993; Encephale 19: 23-8 4. Allebeck, Schizophr Bull 1989; 15: 81-89 5. Dixon et al, J Nerv Ment Dis 1999; 187: 495-502 6. Allison, D., et al. J Clin Psychiatry 1999; 60: 215-220 7. Herran et al, Schizophr Res 2000; 41: 373-381 Sunday, July 26, 2009
  7. 7. Depression, Anxiety and Stress  Each may be associated with an array of similar physical problems  These physical complications may have an enormous impact on the health and well- being of the patient  Depression, anxiety and stress may each complicate physical illnesses and modulate their course, severity and outcome Sunday, July 26, 2009
  8. 8. The Physical Complications of Depressive Disorders Sunday, July 26, 2009
  9. 9. Somatic Symptoms in People with Major Depressive Disorder  Fatigue 86%*  Chest pain 27%  Insomnia 79%*  Sexual symptoms 23%  Nausea 51%*  Pain in extremities 20%  Dyspnea 38%  Dizziness 19%  Palpitations 38%  Abdominal pain 18%  Back pain 36%*  Tinnitus 18%  Diarrhea 29%  Joint or limb pain 16%  Headache 28% Patients presenting in a Psychosomatic Clinic assessed with Cornell Medical Index Questionnaire *Significantly higher % in those with MDD Nakao, M. et al, Psychopathology 2001: 34, 230-5 Sunday, July 26, 2009
  10. 10. Common Complicating Problems in Depression  Smoking  Poor physical activity  Adherence to medical advice  Sleep disturbances Sunday, July 26, 2009
  11. 11. Depressive Disorders in the Physically Ill: Key Points  Depressive disorders are common in the physically ill  Depressive disorders co-occurring with physical illness complicate treatment of both disorders  Depressive disorders and physical illnesses must be treated in parallel Sunday, July 26, 2009
  12. 12. Comorbid Depression Alters the Outcome of Physical Illness  Depressed post-stroke patients  Less compliant with treatment, more irritable and demanding1  Depressed patients following myocardial infarction  Less compliant with rehabilitation programs, longer recoveries and slower return to normal functioning2  Are 2.7 times more likely to die3  Depressed diabetic patients  Poorer glucose control4 1. Ross, E.D. and Rush, A.J. Arch Gen Psychiatry 1981: 38, 1344-1354 2. Guiry, E., et al. Clin Cardiol 1987: 10, 256-260 3. Surtees, P.G. et al. Am J Psychiatry 2008: 165, 515-523 4. Lustman, PJ, et al. Diabetes Care 1988: 11, 605-612 Sunday, July 26, 2009
  13. 13. Increased Mortality Associated With Depression and Physical Illness  Depressed patients have a significantly higher 4- year mortality than non-depressed controls after controlling for severity of physical illness1  Depression increased mortality in 211 hospitalized patients with a life-threatening illness  Depressed patients had significantly poorer outcome over the 28 days following admission — 47% died or had life-threatening complications vs 10% of the non- depressed patients2 Murphy E, et al. Brit J Psych, 1988, 152:347-353. Silverstone PH, J Psychosomatic Res. 1990, 34:6;651-657. Sunday, July 26, 2009
  14. 14. Depressive Disorders and Physical Illness: Possible Associations  Common cause for both  Physical illness “causing” depressive disorder  Depressive disorder “causing” physical illness Sunday, July 26, 2009
  15. 15. The Major Physical Consequences of Depression  Fatigue  Sleep disturbances  Inflammation  Carbohydrate and fat metabolism  Hypothalamic-pituitary-adrenal axis  Cardiovascular disease  Osteoporosis  The immune system Sunday, July 26, 2009
  16. 16. Inflammation 1  A Missing Link Between:  Sleep deprivation1  Circadian rhythm disorders2-5  Stress6  Insulin resistance7-8  Abdominal obesity9  Diabetes mellitus10 1. Liu, H., Wang, G., Luan, G., and Liu, Q. J Thromb Thrombolysis 2008: July http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18597046 2. Shephard, R. J., and Shek, P. N. Can J Appl Physiol 1997; 22, 95-116 3. Dickerson, F., Stallings, C., Origoni, A., Boronow, J., and Yolken, R. Prog Neuropsychopharmacol Biol Psychiatry 2007: 31, 952-5 4. Huang, T. L., and Lin, F. C. Prog Neuropsychopharmacol Biol Psychiatry 2007: 31, 370-2 5. O'Brien, S. M., Scully, P., Scott, L. V., and Dinan, T. G. J Affect Disord 2006: 90, 263-7. 6. Hamer, M., and Stamatakis, E. Physiol Behav 2008: 94, 536-9 7. de Luca, C., and Olefsky, J. M. FEBS Lett 2008: 582, 97-105 8. Heilbronn, L. K., and Campbell, L. V. Curr Pharm Des 2008: 14, 1225-30 9. Nathan, C. Epidemic inflammation: pondering obesity. Mol Med 2008: 14, 485-92 10. Savoia, C., and Schiffrin, E. L. Clin Sci (Lond) 2007: 112, 375-84 Sunday, July 26, 2009
  17. 17. Inflammation 2  Chronic inflammation affects the photic response of the suprachiasmatic nucleus1  Cox-2 inhibition appears promising in the treatment of depression and schizophrenia2  Particulate air pollution is associated with systemic inflammation3  Inflammation is associated with a reduction in heart rate variability, a marker of depression and a major predictor of death after myocardial infarction4  Physical exercise reduces inflammation and improves heart rate variability and mood5 1. Palomba, M., and Bentivoglio, M. J Neuroimmunol 2008: 193, 24- 2. Muller, N., and Schwarz, M. J. Curr Pharm Des 2008: 14, 1452-65 7 3. Liu, L., Ruddy, T. D., Dalipaj, M., Szyszkowicz, M., You, H., Poon, R., Wheeler, A., and Dales, R. J Occup Environ Med 2007: 49, 258-65 4. von Kanel, R., Nelesen, R. A., Mills, P. J., Ziegler, M. G., and Dimsdale, J. E. Brain Behav Immun 2008: 22, 461-8 5. Thompson, A. M., Mikus, C. R., Rodarte, R. Q., Distefano, B., Priest, E. L., Sinclair, E., Earnest, C. P., Blair, S. N., and Church, T. S. Contemp Clin Trials 2008: 29, 418-27 Sunday, July 26, 2009
  18. 18. Inflammation, Sickness Behavior and Depression  Inflammation and cytokines  Cytokine-induced sickness behavior:1  Weakness  Malaise  Listlessness  Disinterest  Poor concentration  Anorexia Myers, J. S. Oncol Nurs Forum 2008: 35, 802-7 Sunday, July 26, 2009
  19. 19. The Physical Consequences of Depression: Insulin Resistance Sunday, July 26, 2009
  20. 20. What is Insulin Resistance? Sunday, July 26, 2009
  21. 21. What is Insulin Resistance?  Insulin resistance is defined as an impaired biological response to insulin1  Insulin resistance is a primary defect in the majority of patients with Type 2 diabetes2  In non-diabetic individuals, insulin resistance, in combination with hyperinsulinemia, has a strong predictive value for the future development of Type 2 diabetes3 1. American Diabetes Association. Diabetes Care 1998;21(2):310–314 2. Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721 3. Bloomgarden ZT. Clin Ther 1998;20(2):216–231 Sunday, July 26, 2009
  22. 22. What is Insulin Resistance?  Insulin resistance is defined as an impaired biological response to insulin1  Insulin resistance is a primary defect in the majority of patients with Type 2 diabetes2  In non-diabetic individuals, insulin resistance, in combination with hyperinsulinemia, has a strong predictive value for the future development of Type 2 diabetes3 Present in ~30-33% of the general population of the USA, but with marked ethnic differences 1. American Diabetes Association. Diabetes Care 1998;21(2):310–314 2. Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721 3. Bloomgarden ZT. Clin Ther 1998;20(2):216–231 Sunday, July 26, 2009
  23. 23. Insulin Resistance Syndrome Synonyms  Metabolic syndrome  (Metabolic) Syndrome X  Dysmetabolic syndrome  Reaven’s syndrome  Multiple metabolic syndrome Sunday, July 26, 2009
  24. 24. The Metabolic Syndrome and the Insulin Resistance Syndromes  Several sets of criteria  Most usually defined in the USA as the presence of 3 or more of the following:  Abdominal obesity  (Waist circumference >40 inches in men; >35 inches in women  Glucose intolerance (fasting glucose ≥110 mg/dL)  Blood pressure ≥130/85 mmHg  Triglycerides >150 mg/dL  Low HDL(Men: <40 mg/dL; women: <50 mg/dL) NCEP ATP III. Circulation. 2002;106;3143. Sunday, July 26, 2009
  25. 25. The Metabolic Syndrome and the Insulin Resistance Syndromes  Several sets of criteria  Most usually defined in the USA as the presence of 3 or more of the following:  Abdominal obesity  (Waist circumference >40 inches in men; >35 inches in women  Glucose intolerance (fasting glucose ≥110 mg/dL)  Blood pressure ≥130/85 mmHg  Triglycerides >150 mg/dL  Low HDL(Men: <40 mg/dL; women: <50 mg/dL) Present in ~22% of the general population of the USA, but with marked ethnic variations NCEP ATP III. Circulation. 2002;106;3143. Sunday, July 26, 2009
  26. 26. Sunday, July 26, 2009
  27. 27. Insulin Resistance Sunday, July 26, 2009
  28. 28. Intra-Abdominal Inactivity Glucose Genetics Medications Obesity Intolerance Cigarette Smoking Aging Fetal Malnutrition Insulin Resistance Sunday, July 26, 2009
  29. 29. Intra-Abdominal Inactivity Glucose Genetics Medications Obesity Intolerance Cigarette Smoking Aging Fetal Malnutrition Insulin Resistance Type 2 Diabetes Sunday, July 26, 2009
  30. 30. Intra-Abdominal Inactivity Glucose Genetics Medications Obesity Intolerance Cigarette Smoking Aging Fetal Polycystic Malnutrition Ovary Syndrome Dyslipidemias Insulin Microalbuminuria Resistance Endothelial Dysfunction QTc Prolongation Dysfibrinolysis ?Certain Macrovascular Malignancies Disease Other Type 2 Non Alcoholic Hypertension Metabolic Effects: e.g. Fatty Liver Hyperuricemia Diabetes Disease Sunday, July 26, 2009
  31. 31. Homeostatis Model Assessment (HOMA) Normal: 100% β-cell function: Insulin resistance (R) =1 β-cell function (%): 20 x Insulin (µU/ml glucose (mmol) - 3.5 Insulin resistance: Insulin (µU/ml) x glucose (mmol) 22.5 Hafner et al. Diabetes Care 1996; 1138-1141 Mathews DR, Hoskeer JP, et al. Diabetologia, 1985; 28:412-419 Sunday, July 26, 2009
  32. 32. Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes Sunday, July 26, 2009
  33. 33. Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes Insulin Resistance CVD= Coronary vascular disease; PCOS = Polycystic ovarian syndrome; NAFLD = Non-alcoholic fatty liver disease Adapted from: ACE Position Statement on the Insulin Resistance Syndrome, Endocr Pract. 2003; 9, 240-252; Reaven GM. Diabetes 1988;37:1595–1607; Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721 Sunday, July 26, 2009
  34. 34. Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes Insulin Resistance Compensatory Hyperinsulinemia Insulin Resistance Syndrome CVD Hypertension Stroke PCOS NAFLD CVD= Coronary vascular disease; PCOS = Polycystic ovarian syndrome; NAFLD = Non-alcoholic fatty liver disease Adapted from: ACE Position Statement on the Insulin Resistance Syndrome, Endocr Pract. 2003; 9, 240-252; Reaven GM. Diabetes 1988;37:1595–1607; Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721 Sunday, July 26, 2009
  35. 35. Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes Insulin Resistance Inadequate Insulin Response + β-cell Compensatory failure Hyperinsulinemia Impaired Glucose Tolerance Insulin Resistance Syndrome Type 2 Diabetes Mellitus CVD Hypertension Retinopathy Stroke Nephropathy PCOS Neuropathy NAFLD CVD= Coronary vascular disease; PCOS = Polycystic ovarian syndrome; NAFLD = Non-alcoholic fatty liver disease Adapted from: ACE Position Statement on the Insulin Resistance Syndrome, Endocr Pract. 2003; 9, 240-252; Reaven GM. Diabetes 1988;37:1595–1607; Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721 Sunday, July 26, 2009
  36. 36. Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes Insulin Resistance Inadequate Insulin Response + β-cell Compensatory failure Hyperinsulinemia Impaired Glucose Tolerance Insulin Resistance Syndrome Type 2 Diabetes Mellitus CVD Hypertension Retinopathy Stroke Nephropathy PCOS Neuropathy NAFLD CVD= Coronary vascular disease; PCOS = Polycystic ovarian syndrome; NAFLD = Non-alcoholic fatty liver disease Adapted from: ACE Position Statement on the Insulin Resistance Syndrome, Endocr Pract. 2003; 9, 240-252; Reaven GM. Diabetes 1988;37:1595–1607; Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721 Sunday, July 26, 2009
  37. 37. The Physical Consequences of Depression: Insulin Resistance  Insulin resistance is common in depression1 and anxiety2  Insulin resistance is associated with obesity, depression, and chronic low-grade inflammation in women with polycystic ovary syndrome3  Insulin resistance syndrome predisposes to the development of depressive symptoms4  There is a complex relationship between antidepressants and insulin resistance5,6 1. Timonen, M., Salmenkaita, I., Jokelainen, J., Laakso, M., Harkonen, P., Koskela, P., Meyer-Rochow, V. B., Peitso, A., and Keinanen-Kiukaanniemi, S. Psychosom Med 2007: 69, 723-8 2. Narita, K., Murata, T., Hamada, T., Kosaka, H., Sudo, S., Mizukami, K., Yoshida, H., and Wada, Y. Psychoneuroendocrinology 2008: 33, 305-12 3. Benson, S., Janssen, O. E., Hahn, S., Tan, S., Dietz, T., Mann, K., Pleger, K., Schedlowski, M., Arck, P. C., and Elsenbruch, S. Brain Behav Immun 2008: 22, 177-84 4. Koponen, H., Jokelainen, J., Keinanen-Kiukaanniemi, S., Kumpusalo, E., and Vanhala, M. J Clin Psychiatry 2008: 69, 178-82 5. Chen, Y. C., Shen, Y. C., Hung, Y. J., Chou, C. H., Yeh, C. B., and Perng, C. H. J Affect Disord 2007: 103, 257-615. 6. Levkovitz, Y., Ben-Shushan, G., Hershkovitz, A., Isaac, R., Gil-Ad, I., Shvartsman, D., Ronen, D., Weizman, A., and Zick, Y. Mol Cell Neurosci 2007: 36, 305-12 Sunday, July 26, 2009
  38. 38. Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance Basal Intra- Peripheral Corticosteroid Abdominal Insulin Insulin Release Fat Levels Resistance Sunday, July 26, 2009
  39. 39. Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance Stress Basal Intra- Peripheral Corticosteroid Abdominal Insulin Insulin Release Fat Levels Resistance Sunday, July 26, 2009
  40. 40. Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance Stress Basal Intra- Peripheral Corticosteroid Abdominal Insulin Insulin Release Fat Levels Resistance Sunday, July 26, 2009
  41. 41. Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance Stimulation Release of Pancreatic of FFA Insulin and TG Release + Stress Reduced Insulin Breakdown Basal Intra- Peripheral Corticosteroid Abdominal Insulin Insulin Release Fat Levels Resistance Sunday, July 26, 2009
  42. 42. Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance Stimulation Release of Pancreatic of FFA Insulin and TG Release + Stress Reduced Insulin Breakdown Basal Intra- Peripheral Corticosteroid Abdominal Insulin Insulin Release Fat Levels Resistance Sunday, July 26, 2009
  43. 43. Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance Stimulation Release of Pancreatic of FFA Insulin and TG Release + Stress Reduced Insulin Breakdown Basal Intra- Peripheral Corticosteroid Abdominal Insulin Insulin Release Fat Levels Resistance Sunday, July 26, 2009
  44. 44. Depression With Comorbid Diabetes  15% to 20% of patients with Type I or Type II diabetes have major depression  Depression in diabetic patients is associated with  Poor compliance with diabetes regimen  Poor glycemic control  Increased risk for microvascular and macrovascular complications Lustman, P. J., Penckofer, S. M., and Clouse, R. E. Curr Diab Rep 2007: 7, 114-22 Sunday, July 26, 2009
  45. 45. Depression With Comorbid Diabetes  Fluoxetine, citalopram and nortriptyline are effective in major depression with comorbid diabetes  Improvement in depression has an independent and clinically relevant beneficial effect on glycemic control  There is increasing evidence that antidepressants may worsen metabolic control1 1. Derijks, H. J., Meyboom, R. H., Heerdink, E. R., De Koning, F. H., Janknegt, R., Lindquist, M., and Egberts, A. C. Eur J Clin Pharmacol 2008: 64, 531-8 Sunday, July 26, 2009
  46. 46. The Physical Consequences of Depression: Cardiovascular Disease  Coronary artery disease is more common in depression, anxiety and stress disorders Sunday, July 26, 2009
  47. 47. Depression and Physical Dysfunction from Coronary Artery Disease (CAD)  Physical dysfunction secondary to CAD linked with:  Number of main coronary vessels stenosed >70% (p<0.03)  Depression (p=0.001)  After 1 year, physical function no longer associated with number of arteries stenosed, but still significantly associated with depression (p<0.001) Sullivan et al. Am J Med. 1997 Sunday, July 26, 2009
  48. 48. Depression and Myocardial Infarction  Patients with depression have 5-fold increased risk of cardiac mortality1  New-onset depression after myocardial infarction doubles mortality over eight years2  The risk is reduced by:  Cardiac rehabilitation3  Some antidepressant medications4 1. Frasure-Smith, N. JAMA 1992: 268, 195 2. Dickens, C., McGowan, L., Percival, C., Tomenson, B., Cotter, L., Heagerty, A., and Creed, F. Psychosom Med 2008: 70, 450-5 3. Milani, R. V., and Lavie, C. J. Am J Med 2007: 120, 799-806 4. Jiang, W. Cleve Clin J Med 2008: 75 Suppl 2, S20-5 Sunday, July 26, 2009
  49. 49. Depression in the Medically Ill: Cerebrovascular Accident  Multiple studies have shown an increased risk of stroke in people with chronic depression1  Depression appears to be an independent risk factor for stroke, though metabolic disturbances and cerebral microvascular disease may yet prove to be the “cause” of both Surtees, P. G., Wainwright, N. W., Luben, R. N., Wareham, N. J., Bingham, S. A., and Khaw, K. T. Neurology 2008 70, 788-94 Sunday, July 26, 2009
  50. 50. Depression and Stroke: Fluoxetine vs. Maprotiline vs. Placebo  52 severely disabled hemiplegic subjects were followed during 2 months of physical therapy1  Greatest improvements in functioning were observed in the fluoxetine group  Fluoxetine yielded significantly larger number of patients with good recovery compared to maprotiline and placebo  Subsequent studies have shown that successful treatment with most SSRIs improve recovery after stroke2 1. Dam M. Stroke. 1996;27:1211-1214 2. Bilge, C., Kocer, E., Kocer, A., and Turk Boru, U. Eur J Phys Rehabil Med 2008: 44, 13-8 Sunday, July 26, 2009
  51. 51. The Physical Consequences of Depression: Osteoporosis  In depression:1  Reduced bone mineral density  Increased risk of fractures  It is unknown if anxiety or chronic stress decrease bone mineral density 1. Mezuk, B., Eaton, W. W., and Golden, S. H. Osteoporos Int 2008: 19, 1-12 Sunday, July 26, 2009
  52. 52. The Physical Consequences of Depression: Cancer  Clinical depression is the most common psychiatric disorder among cancer patients and is associated with significant functional impairment1 1. Hopko, D. R., Bell, J. L., Armento, M. E., Robertson, S. M., Hunt, M. K., Wolf, N. J., and Mullane, C. J Psychosoc Oncol 2008: 26, 31-51 Sunday, July 26, 2009
  53. 53. Depression and Cancer 16 Fluoxetine Desipramine † † * * Mean Change** 12 † † * * 8 † † 4 * † * † 0 HAM-D-17 HAM-A CGI-Severity FLIC **Positive values are used to indicate improvement; *p<0.05 for analysis of change within drug treatment group using Wilcoxon’s signed rank statistic with no allowance for investigator effects; †p<0.05 for analysis of change within drug treatment group using Wilcoxon’s signed rank statistic after adjusting for investigator effects using weighted means. Holland JC et al. Psycho-Oncology. 1998;7(4):291-300 Sunday, July 26, 2009
  54. 54. Effect of Psychosocial Treatment on Survival of Patients with Metastatic Breast Cancer 1.0 Treatment (N=50) Control (N=36) 0.8 Overlapping control and treatment probabilities of survival Probability of Survival 0.6 Some points represent more than 1 case 0.4 0.2 0.0 0 20 40 60 80 100 120 140 Months from Study Entry to Death Spiegel et al. Lancet, 1989, II, 888-891 Sunday, July 26, 2009
  55. 55. Treating Depression in Cancer  Intervention-Depression Care for People with Cancer:  Scotland, UK  Nurse-delivered complex intervention  200 patients, mean age 56.1 years  Reduced:  Depression  Anxiety  Fatigue  Cost-effective Strong, V., Waters, R., Hibberd, C., Murray, G., Wall, L., Walker, J., McHugh, G., Walker, A., and Sharpe, M. Lancet 2008: 372, 40-8 Sunday, July 26, 2009
  56. 56. Major Depression and Medical Comorbidity Evaluation  Consider all symptoms of major depression despite another possible physical cause  Probe for loss of interest or pleasure or psychological symptoms such as guilt or loss of self-esteem  Evaluate medication regimen for drugs that may cause depression Sunday, July 26, 2009
  57. 57. Depressive Disorders In The Physically Ill: Obstacles To Recognition  Attributing depressive symptoms to somatic illness  Denial of depressive experience  Similarity between depressive symptoms and symptoms of other illnesses Sunday, July 26, 2009
  58. 58. Risk Factors For Depressive Disorders In Physical Illness  Female gender  Being unmarried  Living alone  Previous depressive episodes  Certain medical treatments  Severe forms of physical illness Sunday, July 26, 2009
  59. 59. Diagnosing Depressive Disorders In The Physically Ill: Patient’s And Family’s Psychiatric History  Family history of depressive disorders/mania/ hypomania  Family history of suicide/suicide attempt(s)  Previous depressive episodes  Good response to antidepressants in past episodes of mental disorder Sunday, July 26, 2009
  60. 60. Diagnosing Depressive Disorders In The Physically Ill: Patient’s And Family’s Psychiatric History (cont’d)  Previous manic or hypomanic episodes  Previous suicide attempt(s)  History of alcoholism or alcohol abuse and/or substance abuse disorders  Seasonal variation and/or diurnal variation of depressive symptoms Sunday, July 26, 2009
  61. 61. Treatment of Depression and Anxiety in Physical Illness  Antidepressants cause improvement in depression in patients with a wide range of physical diseases significantly more frequently than either placebo or no treatment  Antidepressants are reasonably well-tolerated in patients with physical illness  Increasing evidence suggests that non- pharmacological approaches to treatment are also important Gill D, Hatcher S. In: The Cochrane Library, Issue 2, 1999. Sunday, July 26, 2009
  62. 62. Conclusions  Depression, anxiety and stress are all best seen as systemic disorders with psychiatric symptoms  It is essential to be alert to the possible physical associations of each of these disorders, and to screen and manage them appropriately Sunday, July 26, 2009
  63. 63. Suggested Evaluations and Investigations of People with Depression, Stress and Anxiety Disorders  Evaluations:  Weight and height -> BMI  Measure waist and hips  Blood pressure and pulse - lying and standing  Signs of EPS or tardive dyskinesia  Investigations:  Fasting electrolytes, creatinine, glucose and lipids + measure insulin resistance in high-risk patients  Liver function tests  Thyroid stimulating hormone: if equivocal consider free T3 and CK  Prolactin  Electrocardiogram  (Bone density measurement only if there are other high risk factors)  Despite the evident resource implications, suggest doing these at least annually, and more often if:  Abnormal  There are clinical changes  There are other risk factors present Sunday, July 26, 2009
  64. 64. Health Promotion Interventions Female patients Male patients Reinforce the need for: Reinforce the need for:  Breast self-exam  Annual prostate exam  Does the patient know  When, if ever, has he had how to do a breast exam? a prostate exam?  Annual pap test  Testicular self-exam  When was the last pap smear?  Does the patient know how to do a self-exam?  Mammography  Has she ever had a  PSA, if indicated mammogram?  Has the patient ever had a PSA? Sunday, July 26, 2009
  65. 65. Useful Addresses  Healia.com  www.richardgpettymd.com  rpettyus@aol.com Sunday, July 26, 2009
  66. 66. Additional Data Sunday, July 26, 2009
  67. 67. Concept of the Immune System Adoptive IS Innate IS AP-Cells Monocytes, ... Complement System Th0-Cells IFN-γ IL-4 IL-2 IL-10 IL-6 IL-6 Antibodies Th1-Cells Th2-Cells B-Cells Sunday, July 26, 2009
  68. 68. The Balance of Humoral and Cellular Immune Response Th1 cells Th2 cells cellular immune response humoral Sunday, July 26, 2009
  69. 69. Th1/Th2 in Major Depression Markers of Th1/Th2 Responses in Major Depression Site of cytokine Th1 Th2 expression In-vitro production IFN-γ ↑ IL-6 ↑↑ Peripheral sIL-2R ↑↑ IL-6 ↑↑ IFN-γ ↑ IFN-γ ↑⇒ TRP↓ CSF sIL-2R ↑ IL-6↓ sIL-6R ↓ Hypothesis A Th1-serotonin-link in A Th2-dominance or an overactivation suicidal MD? of monocyte/macrophage system in non-suicidal MD? Sunday, July 26, 2009
  70. 70. Immune Changes in Depression T-cell Macrophage activation activation IFN-γ IL-1 TNF-α IL-6 IL-1ra IL-6R Autoimmune response PGE2 Leucocyte number Cortisol Acute phase proteins Adapted from: Song, Leonard, 2000 Sunday, July 26, 2009
  71. 71. Interleukine 6 (IL6)  Marker of monocyte activation  Modulation of HPA axis  Elevation in depression Sunday, July 26, 2009
  72. 72. Immune-Neurotransmitter Interaction in Depression T-cell Macrophage activation activation IFN-γ IL-1 TNF-α IL-6 Tryptophan degradation 5-HT transporter 5-HT NE ? PGE2 5-HT Cortisol Sunday, July 26, 2009
  73. 73. The Relationship Between the Th1 Cytokine IFN-g and Serotonin Metabolism Tryptophan IFN-g + IDO + Kynurenine Serotonin KYN-Hydrox. Quinolinate 5-Hydroxyindole acetic acid (IDO = indoleamine 2,3-dioxygenase; KYN-Hydrox. = kynurenine hydroxylase) Sunday, July 26, 2009
  74. 74. Possible Ways For Pro-inflammatory Wichers & Maes, 2001 Sunday, July 26, 2009
  75. 75. Cytokine-Neurotransmitter Interaction of Antidepressants IL-10 IFN-γ IL-1 TNF-α IL-6 Antidepressants 5-HT transporter 5-HT NE PGE2 Cortisol Sunday, July 26, 2009
  76. 76. Inflammation, Prostaglandin E2 and Depression  IL-6 (PGE2↑) and TNF-α (COX-2 expression↑) increased in a subgroup of depressive patients  Salivary concentration of PGE2 increased in major depression (Ohishi et al, 1987; Nishino et al, 1988)  Increased PGE2 production in lymphocytes of major depression (Song et al, 1998)  PGE2 reduces noradrenaline-release and stimulates the HPA-axis in the CNS (Song & Leonard, 2000)  Antidepressants inhibit PGE2-synthesis (Mtabaji et al, 1977) Sunday, July 26, 2009

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