• TCAs are associated with increased appetite, weight gain and hyperglycaemia• Irreversible MAOIs have a tendency to cause extreme hypoglycaemicepisodes and weight gain• Nortriptyline improved depression but worsened glycaemic control indiabetic patients in one study. Overall improvement in depression had abeneficial effect on HbA 1c . Clomipramine reported to precipitate diabetes• Long-term use of TCAs may increase risk of diabetes • Irreversible MAOIs have a tendency to cause extreme hypoglycaemicepisodes and weight gain• No known effects with moclobemide
Guide-Dr. D.K.Sharma Professor & Head, Dept of Psychiatry,Govt Medical College, Kota
1. Introduction2. Co-morbidity3. Presentation of Depression in Clinical Practice4. Diagnosis of Depression in medical comobidity5. Depression with CAD6. Depression with Diabetes7. Treatment of Depression with CAD8. Treatment of Depression with Diabetes
The Mind & The Body When DESCARTES uttered his famous dictum “cogito ergo sum ” which separated mind from body, he did medicine a favour Now, however, the idea that mind & body are separate is holding medicine back from fully exploring the interactions among mind, body & brain The idea constrains our knowledge of how depression & anxiety complicate illness such as diabetes, heart disease, cancer etc.
It also obscures the obvious fact that medical treatment must encompass CARE AS WELL AS CURE – involve the person with the illness & not just the disease in the body Our bodies are merely the structures which house the mind. “MIND” is the controlling power & so we must keep it healthy to the maximum extent possible “We can’t think of a healthy body without a healthy mind”
“It is much more important to know what sort of a patient has a disease than what sort of disease a patient has” - Sir William Osler (1849-1919)
Depression is a disorder of mood/feeling- That is unpleasant There is feeling of sadness Misery Which affects day to day activities of life
Depression for psychiatrist is what “common cold” is for physicians! Lifetime prevalence - 10% for males & 20% for females Point prevalence - 5% for males & 10% for females.
Burden in Disability-Adjusted Life Years (DALYs)Rank 20001 Rank Estimated 202021 Lower respiratory infections 1 Ischemic heart disease2 Perinatal conditions 2 Unipolar major depression3 HIV/AIDS 3 Road traffic accidents4 Unipolar major depression 4 Cerebrovascular disease5 Diarrheal diseases 5 Chronic obstructive pulmonary diseaseYear 1992 : Total cost of depression estimated to be $ 44 billion, of which only 3% was due to drug costYear 1997 : Annual economic burden of depression was $ 65 billionYear 2000 : 4th most frequent cause of lost work yearsYear 2003 : Total cost of depression estimated to be $ 83 billion 1World Health Report 2001. Mental Health: New Understanding, New Hope. Geneva: World Health Organization; 2001. 2Murray CJL, Lopez AD, eds. The Global Burden of Disease. Boston: Harvard University Press; 1996. National Ambulatory Care Medical Survey: 1997 summary. Adv Data 1999; 305: 1-28. In: Nurnberg GH, et al. JAMA 2003; 289: 56- 64. Martin Korn and Rachel Pollock, XXIIIrd Congress of the CINP; Judd LL, et al. Am J Psychiatry 1996
DEPRESSION: EPIDEMIOLOGY (INDIAN DATA) Common Disorder PREVALENCE Overall: 15.1% 5.9% to 19.3%Prevalence of depression in a large urban South Indian population--the Chennai Urban Rural EpidemiologyStudy (CURES-70). Poongothai S, Pradeepa R, Ganesan A, Mohan V.Madras Diabetes Research Foundation & Dr. Mohans Diabetes Specialities Centre, WHO CollaboratingCentre for Non-Communicable Diseases-Prevention and Control, Gopalapuram, Chennai, India.
Consequences Challenges» Increased severity of symptoms » Diagnostic» Poorer psychosocial » Therapeutic functioning» Poorer treatment outcomes» Chronicity» High risk of suicidal ideation Brown C et al, Am J Psychiatry. 1996. David Dunner, International Clinical Psychopharmacology 1998.
Lifetime Prevalence Rates Major AnxietyDepression 59% Disorders Kessler et al, JAMA, 2003.
Medically ill (6% – 14%) Prevalence of Primary Care (5% – 10%) Major Depression Community (2% – 5%)Also, Depression is second only to hypertension as the most common chronic condition encountered in general medical practice. Therefore-Identification and effective treatment of co-morbid depression - ESSENTIALWayne J. Katon. Available from: URL: http://www.medscape.com/viewprogram/554(last accessed on1.10.04).Mary A. Whooley and Gregory E. Simon. The New England Journal Of Medicine 2000; 343:1942-1950.
Medical Illness Prevalence Chronic pain 35% to > 50% Myocardial infarction 20% Diabetes mellitus 25% Parkinson’s disease 30% to 50% Terminal solid tumors 25% to 38% Stroke 27% to 35% Epilepsy 20% to 30% Renal disease 5% to 22%www.preskorn.com Last accessed on 30.12.02; Goodnick PJ; Kumar A;Henry J; Buki VMV; Goldberg R: Psychopharmacol Bull 1997; 33(2): 261-4.
Medical Illness Risk for Depression Cardiovascular disease X3 Diabetes mellitus X2-3Ziegelstein RC. JAMA 2001; 286: 1621-1627. Musselman DL, Evans DL, Nemeroff CB. Arch Gen Psychiatry 1998;55: 580 592. 5. Anderson RJ, Freedland KE, Clouse RE et al. Diabetes Care 2001;24: 1069-1078. Egberts AC, Leufkens HG, Hofman A et al. Int Clin Psychopharmacol 1997; 12: 217-223.
A. Psychological Symptoms Low mood Loss of drive, energy & interest Poor Concentration Tearfulness Irritability Apprehensive attitude Guilt feeling Suicidal ideas
C. Social Symptoms Decreased social interaction Poor work performance Decline in problem solving ability Neglect of family & friends Social Withdrawal
Depression is frequently undiagnosed & untreated in medical & primary care setting despite its frequency, negative effect on health & treatability
CAUSES of missing diagnosis of MDD in general clinical practice:- Lack of time-Most medical visits last less than 15 min. & lot many issues are addressed in this brief time Lack of privacy in medical setting limits disclosure or elaboration of symptoms Lack of time & skill on part of clinician to manage emotionality which may be triggered after touching an emotional issue Pt’s may not recognize depressive symptoms & may attribute them to their medical condition (as many symptoms of Depression are similar to those of medical illness)
Missing diagnosis of MDD in medical setting may result in Lost opportunity to: -Improve quality of life -Decrease risk of suicide -Shortened hospital stay -Improved treatment compliance
NEED FOR A SCREENING INSTRUMENT Lloyd Williams et. al found that asking patients in a palliative care unit a single question “are you depressed” with a response choice of “yes” or “no” yielded a sensitivity of only 55% & specificity of 74% for diagnosis of MDD
So there is a need for accurate & rapid methods of screening for Depression in medical settings Screening instruments most widely used:1.Center for Epidemiologic Studies Depression Scale (CES-D)2.Hospital Anxiety & Depression Scale(HADS)3.Beck Depression Inventory-II (BDI-II)4.Patient Health Questionairre-9 (PHQ-9), this is self administered version of PRIME-MD
There is overlap b/w symptoms of depression & constitutional symptoms of med illness (anorexia, fatigue, weight loss, insomnia, psychomotor retardation & diminished concentration) Different approaches have been proposed to overcome difficulties due to this overlap:-1. Inclusive approach2. Exclusive approach3. Etiologic approach4. Substitutive approach
1) Inclusive approach:- -includes all symptoms of depression, regardless of their cause -High rate of false positives2) Exclusive approach:- -Simply excludes all the overlapping symptoms -Low sensitivity3) Etiologic approach:- -requires clinicians to determine causality and reject symptoms when they are “clearly due to a physical condition” -Difficult to administer
4) Substitutive approach (Endicott’s criteria):- -Suggests replacing of Physical symptoms with Psychological symptoms -Studies have found this to be both reliable & valid Endicott’s criteriaDSM-IV criteria Substitutive criteriaAppetite disturbance Depressed appearanceSleep disturbance Social withdrawalLoss of energy Self-Pity or PessimismDifficulty in concentrating Non-reactive mood
Major depressive disorder ◦ Present in as many as 20% patients with CAD More than 3 out of 4 individuals with immediate post-MI depression are still depressed 3 months later Ziegelstien R JAMA 2001;286:1621-1627 Taylor D. Acta Psychiatr Scand 2008; 118: 434
Depression associated with 64% ↑ risk for CAD Anger/hostility associated with: ◦ 20% ↑ risk incident CAD in initially healthy individuals ◦ Poor prognosis in CAD patients Relative risk of developing CAD in patients with depression as compared to general population: ◦ 1.81 (95% CI: 1.53 – 2.15) Relative risk of death due to cardiovascular events: ◦ 1.80 (95% CI: 1.5–2.15)Taylor D. Acta Psychiatr Scand 2008; 118: 434.
Thus, there is an established association between: ◦ Depression & development of CAD (Depression is an independent risk factor for heart disease) ◦ Depression & cardiovascular mortality (Depression is an imp. independent predictor of death even after CABG)Taylor D. Acta Psychiatr Scand 2008; 118: 434.
Increased morbidity and mortality Significant risk factor for stroke, myocardial infarction (MI), and death in elderly hypertensive patients Four times higher rates of cardiac mortality in patients with acute MI Lack of motivation to initiate & sustain heart-healthy lifestyle changes (such as smoking cessation, modification of diet & an exercise program) Poor prognosis in CAD disease
Depression platelet serotonin levels activation of HPA axis* parasympathetic sympathetic platelet coronary tone tone activation vasoconstriction thrombogenesis Lower threshold for ventricular fibrillation (arrhythmia) May lead to sudden cardiac deathMusselman DL, Evans DL, Nemeroff CB. Arch Gen Psychiatry 1998; 55: 580-592. Musselman DL. Tomer A. Manatunga AK etal. Am JPsychiatry 1996; 153:1313-1317. Stagliano NE, Zhao W, Pardo R, Dwanjee MK, Ginsberg MD, Dietrich WD. Cereb Blood Flow Metab1997; 17(11): 1182-1190. Finkel MS, Laghrissi-Thode F, Pollock BG, Rong J. Psychopharmacol Bull. 1996; 32(4): 653-658. Carney RM,Freedland KE, Rich MW, Smith LJ, Jaffe AS. Am J Med 1993; 95: 23-8. Murberg TA, Bru E, Aarsland T, Svebak S. Int J Psychiatry Med1998; 28: 273-91. Koenig HG. Gen Hosp Psychiatry 1998; 20: 29-43. Fraticelli A. Arch Gerontol Geriatr 1996; 23: 225-38. KrumholzHM, Butler J, Miller J etal. Circulation 1998; 97:958-64. Con AH, Linden W, Thompson JM, Ignaszewski A. J Cardiopulmonary Rehabil1999; 19: 152-61. Frasure-Smith N. Lesperance F. JAMA 1993; 270(15): 1819-25. Carney RM, Rich MW; teVelde A, Saini J, Clark K,Jaffe AS. Am J Cardiol 1987; 60:1273-5. McKhann GM, Borowicz LM, Goldsborough MA, Enger C, SeInes OA. Lancet 1997; 349:1282-4.
Depressed patients with coronary disease ↓ Significantly lower HRV (Indicates abnormally low parasympathetic tone with or without high sympathetic input to heart) ↓ Independent predictor of increased mortality in patients after MIZiegelstien R JAMA 2001;286:1621-1627
Cardiovascular Benefits of Treating Depression SSRIs platelet serotonin levels Platelet Coronary activation thrombosis Overall in the mortality and morbiditySchlienger Raymond G; Meier Christoph R: Am J Cardiovasc Drugs 3(3): 149-62, 2003.
Correlation Between Depression and Diabetes Mellitus Increased release of counter-regulatory hormones Depression Catecholamines Glucocorticoids Glucagon Growth Hormone Decreased action of insulin Increased blood & Increased insulin resistance glucose levels Depression associated insulin resistance (DAIR) • Could double the risk of type 2 diabetesDL Musselman et al., Bio Psychiatry 2003; 54:317-329. • may increase the risk of CADPatrick J. Lustman & Ray E, Journal of Psychosomatic • may increase diabetic complicationsResearch 53 (2002) 917-924.
Higher risk of depression in diabetic patient who ◦ Have less education ◦ Unmarried ◦ Poor social support ◦ Experience chronic stressors Young women with diabetes had up to nine times risk for depression than their male counterpart Adolescent with diabetes have up to three fold greater chance of depression, than youth without diabetes Children with diabetes have two fold greater prevalence of depression
Altered cerebral glucose utilization is seen in left lateral prefrontal cortex & it shows correlation with severity of depressive symptoms Diabetic pts have higher pro-inflammatory cytokines (Il-6) released by adipose tissue, monocytes & macrophages – ◦ Interfere with insulin action ◦ Induce sickness behavior including fatigue, anorexia, anhedonia, decreased psychomotor activity etc. Stress & neuroendocrine mediators influence hippocampal neuronal plasticity depressive symp.
INCREASED LEVEL OF DEPRESSIVE SYMPTOMS Less Poor drug Functionaladherence to compliance impairmentdiabetic diet Poorer Multiple glycemic diabetic control complications INCREASED HEALTHCARE COST
Studies have found that insulin resistance and resultant hyperinsulinemia resolve when patient recover from depression Altered cerebral glucose utilization is also reversed with successful antidepressant treatment So, Treatment of Depression in Diabetes - Essential
Drug Efficacy inDrug Class Safety Tolerability interactions CV Patients Not TCA x x x demonstrated SSRI √ √ No to Minimal √ Not SNRI x x √ demonstrated Not Not NaSSA √ √ demonstrated demonstrated Not NDRI √ √ Minimal demonstrated
No TCA should be used, as consequences of their use ( HR, risk of orthostatic hypotension, and PR & QTc prolongation) may be fatal The only antidepressants shown to be safe and effective in post-MI patients are SSRI’s (Sertraline,Escitalopram,fluoxetine,paroxetine)Goodnick PJ, Hernandez M. Expert Opin Pharmacother 2000; 1: 1367-1384.
Context: MDD occurs in 15% to 23% of patients with acute coronary syndromes Constitutes an independent risk factor for morbidity and mortality No published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable IHD Objective: To evaluate the safety and efficacy of sertraline for the treatment of MDD in patients hospitalized for acute MI or unstable angina and free of other life-threatening medical conditionsGlassman AH, et al; JAMA 2002
Sertraline was safe and well-tolerated Sertraline treatment was not associated with any significant change in » Blood pressure » Heart rate » Arrhythmias » ECG parameters Incidence of severe CV events was numerically lower among patients receiving sertraline (14.5% vs 22.4%)Glassman AH, et al; JAMA 2002
While treating CAD, look for co morbid Depression Detect Depression and treat it at the earliest All patients with depression should be advised to take steps to reduce behaviors associated with CA disease TCAs should be avoided in patients with/at risk of CAD SSRIs (Sertraline) are the Drug of choice for Depression & Co-morbid CAD Treatment of depressive symptoms improves medication adherence in patients after AMI Better outcome for CAD if Depression is treated effectively
All patients with a diagnosis of depression should be screened for diabetes In those who are diabetic- Use SSRIs first line; most data support fluoxetine & sertraline. SNRIs are also likely to be safe but there are fewer supporting data Avoid TCAs and MAOIs if possible due to their effects on weight and glucose homeostasis Monitor blood glucose carefully when antidepressant treatment is initiated, when the dose is changed and after discontinuation -Maudsley Prescribing Guidelines 10th edition
Depression is a disorder of mood/feeling & it would be 2nd largest cause of DALY by the year 2020 Frequently associated with other major medical/surgical illnesses Cases are usually missed due to misconceptions & misidentifications Overlap of somatic symptoms makes accurate diagnosis difficult Depression is a disorder that needs to be treated simultaneously Depression & CAD as well as Depression & DM have bidirectional relationship
SSRIs are the “drug of choice” Treatment should be started as early as possible ◦ Not only to get relief from psychological symptoms ◦ But also to avoid complications or achieve cure of physical illness