This document discusses depression that occurs comorbidly with medical illnesses such as cardiovascular disease and diabetes. It notes that depression is common in patients with these conditions, affecting around 20% of those with CAD and 25% of those with diabetes. Depression is associated with worse health outcomes in these patients, including increased mortality and morbidity, poorer treatment adherence, and worse prognosis. The document explores some of the biological mechanisms of this association, such as effects on the autonomic nervous system, HPA axis, platelet activation and insulin resistance. It emphasizes the need for screening and treatment of depression in medically ill patients in order to improve their overall health.

1. Guide-Dr. D.K.Sharma
Professor & Head,
Dept of Psychiatry,
Govt Medical College,
Kota

2. 1. Introduction
2. Co-morbidity
3. Presentation of Depression in Clinical Practice
4. Diagnosis of Depression in medical comobidity
5. Depression with CAD
6. Depression with Diabetes
7. Treatment of Depression with CAD
8. Treatment of Depression with Diabetes

4.  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.
The Mind & The Body

5.  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”

6. “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)

7. Depression is a disorder of mood/feeling-
 That is unpleasant
 There is feeling of sadness
 Misery
 Which affects day to day activities of life

9.  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.

10. Rank 20001 Rank Estimated 20202
1 Lower respiratory infections 1 Ischemic heart disease
2 Perinatal conditions 2 Unipolar major depression
3 HIV/AIDS 3 Road traffic accidents
4 Unipolar major depression 4 Cerebrovascular disease
5 Diarrheal diseases 5 Chronic obstructive
pulmonary disease
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
Burden in Disability-Adjusted Life Years (DALYs)
Year 1992 : Total cost of depression estimated to be $ 44 billion, of which
only 3% was due to drug cost
Year 1997 : Annual economic burden of depression was $ 65 billion
Year 2000 : 4th most frequent cause of lost work years
Year 2003 : Total cost of depression estimated to be $ 83 billion

11. National Prevalence rates for Five mental disorders
(Rate/1000 median, range and no.of studies)
Schizophrenia
Affective Disorders
Depression(Psychotic
& neurotic)
Anxiety Disorders
Hysteria
Mental Retardation
Rural 3.6
Urban 2.5
Rural 37.4
Urban 33.7
Rural 15
Urban 16
Rural 7
Urban 3.1
Rural 3.7
Urban 9
Rural+Urban
2.5
1.1-14.2
n=13
34
0.5-53
n=15
16.5
11-70
n=8
3.3
2.5-17
n=7
5.3
1.4-25.3
n=10

12. 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 Epidemiology
Study (CURES-70). Poongothai S, Pradeepa R, Ganesan A, Mohan V.
Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating
Centre for Non-Communicable Diseases-Prevention and Control, Gopalapuram, Chennai, India.

14. »Increased severity of symptoms
»Poorer psychosocial
functioning
»Poorer treatment outcomes
»Chronicity
»High risk of suicidal ideation
Challenges
Consequences
» Diagnostic
» Therapeutic
Brown C et al, Am J Psychiatry. 1996.
David Dunner, International Clinical Psychopharmacology 1998.

16. Kessler et al, JAMA, 2003.
Lifetime Prevalence
Rates
Anxiety
Disorders
Major
Depression 59%

17. 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 - ESSENTIAL
Medically ill (6% – 14%)
Primary Care (5% – 10%)
Community (2% – 5%)
Prevalence of
Major
Depression
Wayne J. Katon. Available from: URL: http://www.medscape.com/viewprogram/554(last accessed on
1.10.04).
Mary A. Whooley and Gregory E. Simon. The New England Journal Of Medicine 2000; 343:1942-1950.

18. 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.

19. Medical Illness Risk for Depression
Cardiovascular disease X 3
Diabetes mellitus X 2 - 3
Ziegelstein 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.

21. A. Psychological Symptoms
 Low mood
 Loss of drive, energy & interest
 Poor Concentration
 Tearfulness
 Irritability
 Apprehensive attitude
 Guilt feeling
 Suicidal ideas

22. B. Somatic Symptoms
 Dejected look
 Psychomotor retardation
 Insomnia
 Weight loss
 Musculo-Skeletal pains
 Headache
 G.I. disturbances- gastric fullness
 Cardiovascular symptoms- palpitations

23. C. Social Symptoms
 Decreased social interaction
 Poor work performance
 Decline in problem solving ability
 Neglect of family & friends
 Social Withdrawal

24.  Depression is frequently undiagnosed &
untreated in medical & primary care setting
despite its frequency, negative effect on
health & treatability

25. 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)

26.  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

27. 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

28.  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

29.  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 approach
2. Exclusive approach
3. Etiologic approach
4. Substitutive approach

30. 1) Inclusive approach:-
-includes all symptoms of depression, regardless
of their cause
-High rate of false positives
2) Exclusive approach:-
-Simply excludes all the overlapping symptoms
-Low sensitivity
3) Etiologic approach:-
-requires clinicians to determine causality and
reject symptoms when they are “clearly due to a
physical condition”
-Difficult to administer

31. 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 criteria
DSM-IV criteria Substitutive criteria
Appetite disturbance Depressed appearance
Sleep disturbance Social withdrawal
Loss of energy Self-Pity or Pessimism
Difficulty in concentrating Non-reactive mood

32. CVD DEPRESSION
Depression & CVD

33. DEPRESSION CVD

34.  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

35.  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.

36.  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.

37. Depression as a Risk Factor

38. Depression as a Risk Factor

40.  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

41.  parasympathetic
tone
 sympathetic
tone
Lower threshold for ventricular fibrillation
(arrhythmia)
May lead to sudden cardiac death
Musselman DL, Evans DL, Nemeroff CB. Arch Gen Psychiatry 1998; 55: 580-592. Musselman DL. Tomer A. Manatunga AK etal. Am J
Psychiatry 1996; 153:1313-1317. Stagliano NE, Zhao W, Pardo R, Dwanjee MK, Ginsberg MD, Dietrich WD. Cereb Blood Flow Metab
1997; 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 Med
1998; 28: 273-91. Koenig HG. Gen Hosp Psychiatry 1998; 20: 29-43. Fraticelli A. Arch Gerontol Geriatr 1996; 23: 225-38. Krumholz
HM, Butler J, Miller J etal. Circulation 1998; 97:958-64. Con AH, Linden W, Thompson JM, Ignaszewski A. J Cardiopulmonary Rehabil
1999; 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.
 platelet
activation
 coronary
vasoconstriction
 thrombogenesis
 activation of
HPA axis*
Depression
 platelet serotonin levels

42. 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 MI
Ziegelstien R JAMA 2001;286:1621-1627

43. Cardiovascular Benefits of Treating
Depression
 Coronary
thrombosis
 Platelet
activation
Overall  in the mortality and morbidity
 platelet serotonin
levels
SSRIs
Schlienger Raymond G; Meier Christoph R: Am J Cardiovasc Drugs 3(3): 149-62, 2003.

44. Depression
Diabetes

46. DEPRESSION
DIABETES
MELLITUS

47. Correlation Between Depression
and Diabetes Mellitus
Depression
Increased release of counter-regulatory
hormones
Catecholamines Glucocorticoids
Glucagon Growth Hormone
Increased blood
glucose levels
Decreased action of insulin
&
Increased insulin resistance
Depression associated insulin
resistance (DAIR)
• Could double the risk of type 2
diabetes
• may increase the risk of CAD
• may increase diabetic complications
DL Musselman et al., Bio Psychiatry 2003; 54:317-329.
Patrick J. Lustman & Ray E, Journal of Psychosomatic
Research 53 (2002) 917-924.

48. DEPRESSION
DIABETES
MELLITUS

49.  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

50.  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.

51. DEPRESSION
DIABETES
MELLITUS

52. INCREASED LEVEL OF
DEPRESSIVE SYMPTOMS
Less
adherence to
diabetic diet
Poor drug
compliance
Functional
impairment
Poorer
glycemic
control
Multiple
diabetic
complications
INCREASED
HEALTHCARE
COST

53.  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

55.  Antidepressant Medications
» Selective Serotonin Reuptake Inhibitiors (SSRIs)
» Tricyclic Antidepressants (TCAs)
» Other Antidepressants
 Psychotherapies
» Cognitive
» Cognitive/ behavioral
» Dynamic
» Interpersonal
 Combined medication/ psychotherapy
 ECT- suicidal ideation, resistant dep.
IMS America, November 2000; Depression in Primary Care, 2 1993.

56. Sedation,drowsiness
Skin rashes,weight gain
Dry mouth,blurred vision
constipation,urine retention
Muscle twitching
Palpitations,postural
hypotension,
sweating
Imipramine, Amitryptiline, Clomipramine
SE

57. MAO inhibitors- Side Effects
Liver inflammation
Heart attack
Stroke
Seizures SE
Moclobemide, Tranylcypromine

58. SSRI’s- Side Effects
Mental agitation, anxiety
Panic attacks
Akathisia, psychomotor retardation
Mild parkinsonism, dystonia
Sexual dysfunction, apathy
Nausea, vomiting,
increased bowel motility
Cramps, diarrhea
SE
Sertraline, citalopram, paroxetine,fluoxetine,fluvoxamine

59. Sustained increase in
BP
Contraindicated with
MAO inhibitors
Gastrointestinal side effects
nausea, vomiting
Rigidity & tremor inducing
Venlafaxine, Duloxetine, Desvenlafaxine
SE

60. Weight gain Drowsiness
Mirtazapine
SE

62. Drug Class Safety Tolerability
Drug
interactions
Efficacy in
CV Patients
TCA x x x
Not
demonstrated
SSRI √ √ No to Minimal √
SNRI x x √
Not
demonstrated
NaSSA √ √
Not
demonstrated
Not
demonstrated
NDRI √ √ Minimal
Not
demonstrated

63.  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.

64. 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 conditions
Glassman AH, et al; JAMA 2002

65. 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

66.  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

68.  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

69. B. SSRIs Doses
1. Sertraline 50–200 mg/day
2. Citalopam 20–60 mg/day
3. Escitalopam 10–30 mg/day
4. Fluoxetine 20-60 mg/day
5. Fluvoxamine 100–300 mg/day
6. Paroxetine 20–50 mg/day

70.  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

71.  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