Dr P.

KasiKrishnaRaja DPM DNB

Asst. Professor of psychiatry
Department of Psychiatry
IRT-Perundurai Medical College &
Consultant Psychiatrist-Erode
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Objectives
Epidemiology of depression and anxiety in
Medical illness
Understand the bidirectional effects
Know the barriers in recognition and effects of
depression and anxiety on medical illness
Learn how to recognize depression and
anxiety & understand the treatment options

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Depression
Epidemiology
Depression is estimated to affect 340
million people globally
Depression is very often a chronic and
recurrent illness
Earlier Indian studies have reported
prevalence rates of depression that vary
from 21–83% in primary care practices
In the CURES study conducted at
chennai, 25,455 subjects participated in
this study.

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 DSM-IV Diagnostic Criteria for
Major Depressive Episode
Presence of at least 5 of the following
symptoms during the same 2-week period
that is a change from previous functioning:
 Depressed mood*
 Loss of interest or pleasure*
 Change in appetite and/or weight
 Insomnia or hypersomnia
 Psychomotor agitation or retardation
 Fatigue or loss of energy
 Feelings of worthlessness or guilt
 Poor concentration or indecisiveness
 Suicidal ideation

* At least one of the symptoms must be present: 1) depressed mood or 2) loss of interest or pleasure.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th Ed, Text
Revision. Washington, DC: American Psychiatric Association; 2000. 6
 The global burden of disease,
1990−2020
Lower Respiratory Heart Diseases
Infections Depression
Diarrheal Diseases Traffic accidents
Perinatal conditions Cerebrovascular D/O
Depression COPD
Heart Diseases Lower Respiratory
Cerebrovascular D/O Infections

Lopez et al :Global burden of disease and risk factors, Oxford

University Press, New York (2006) 7
Depression In Primary
Care
Prevalence of Affective d/o in Medically ill
patients is twice that of General populations
Medical Disease is a risk factor itself for
Depression
Rates of Depression increases with Acuity
of care from low 9% in general population
to 30% in acutely hospitalized patients

Fava: J clin Psych Primary Care Companion

2005 8
Likelihood of Depression Increases with
No. of Physical Symptoms at Presentation
70
Depression Likelihood /Percentage

60

50

40
Series1
30

20

10

0
0-1 2 to 3 4 to 5 6 to 8 >9
No. of Physical Symptoms

Kroenke K, et al. Arch Fam Med

1994 9
disorder
in different medical conditions

Per
cent

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Are Depressed patients more
likely to be medically ill?
1500 Depressed Patients Disease/ System Prevalence
were evaluated for General %
Medical Conditions
Musculo skeletal 43%
Total prevalence was 53%
Those with older age, Lower Respiratory 32%
income, unemployment,
limited education and longer Heart 29%
duration of depression were
at higher risk Upper GI 26%
Neurological 25%

Endocrine 24%

Yates et al, Gen Hosp Psych

2004 STAR-D Study 11
Barriers in Diagnosing Depression
in Medically Ill
Patients and families
Physicians
Diagnostic

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Barriers in Diagnosing Depression in
Medically Ill
Patients and families

Patient's own belief systems, Knowledge and

awareness
Too busy with medical problems
Trying to act tough
Not to add burden on family
Do not want to deal with it now
Family minimizing depression

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Barriers in Diagnosing Depression in
Medically Ill
Physician factors
Not aware of the pathoplastic effects of
depression.
Depression is transient
Depression is secondary to underlying illness /
Medications
Patient already has a diagnosis of depression
or seeing a MH provider
I need to focus on medical illness first

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Barriers in Diagnosing Depression
in Medically Ill--Diagnostic issues

Overlap of depressive symptoms can be

accounted for medical Illness
Negative behaviors may be considered as
reaction to illness or rebellious behavior
against illness
DSM IV does not give you any guidance

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Causes of Depression in Medical
Illness
Psychological: Grief & loss of functioning,
disability appearance, being a burden, Death
anxiety and narcissistic injury
Social: Financial issues, educational issues,
limited resources
Medical: Bidirectional theory i.e. one illness
affects other, Direct effects of depression on
medical illness, Is depression a common
symptoms of serous medical illness?
Iatrogenic: Medications, Restraints and wrong
doings

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Cost of Depression
Who pays for it?
Patients
Families
Health Care Provider
System

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Cost of Depression
to Patients
Unable to cope effectively
Affects nutrition, Rx adherence, self care
More likely to have adverse reaction to
medications
Poor physical functioning
Increased Morbidity and mortality

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Cost of Depression
Families
Increased burden
Patient being aloof from family causing more
guilt and anxiety
Impaired relationship
Increased risk of violence and neglect

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Cost of Depression
Health Care Providers
More likely to order work up
Feelings of detachment
May give up early
Feelings of being a failure or not doing
enough

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System
Increased use of resources
Increased mortality and morbidity

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Increased Use of the
Resources

Comorbid
Illnesses

Simmons: Bio. Psychiatry

2003 22
Average costs per day of follow-up and type of inpatient stay for subjects with
depressive symptoms (Geriatric Depression Scale [GDS] >=6) vs without
depressive symptoms (GDS,<6)

Bula, C. J. et al. Arch Intern Med 2001;161:2609-2615.

126$ X 365=$45,990 vs. 175.70$ X

365=$64,130
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Are Depressed Patients Likely to
Die Early?

Review of 57 studies showed 52% as positive,

22 % negative and 26% Neutral.
Depression increases death by natural course
and Cardiovascular Diseases.
Men were at higher risk
Depression does not increase the risk of
death by cancer.

Lawson: Psychosomatic Medicine

1999

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 70

60

50 47.4%
Deaths (%)

40 *
29.8%
30

20

10

0
Depressive Disorder No Depressive Disorder
n = 57 n = 315

*P < 0.05

Rovner BW, et al. JAMA. 1991;265:993-996.

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 Depression and Coronary Artery
Disease
Depression (Barefoot and Schroll 1996; Ford et
al.1998; Lett et al. 2004) and anxiety (Strik et al.
2003) appear to be independent risk factors for the
development of coronary artery disease.
Subsyndromal depressive symptoms also correlate
with an increased risk of cardiovascular mortality
(Frasure-Smith et al.1995).
Even more impressively, negative mood appears to
predict long-term cardiac-related mortality
following myocardial infarction (MI), independently
of cardiac disease severity (Frasure-Smith and
Lesperance 2003a, 2003b).

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Prevalence of Depression is
Higher

Jiang et al AM J Heart 2005

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Pathophysiology of Depression in
CAD
Social, Behavioral causes (lifestyle, compliance,
smoking, other risks)
Biological: Depression causes increased HPA
activation leading to increased Cortisol
Depression lowers heart rate variability due to
increased sympathetic tone
Depression plays a role in subacute inflammatory
process : CRP and IL-6
Common link of 3 Omega FA in Depression and
CAD
Depression causes platelet activation and
aggregation
Jiang et al AM J Heart 2005

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Can Depression in Early Life Lead
to CAD?
Most studies say “yes”
Ford studied Depression in Medical students
for 26 years. Study showed that those who
were depressed at some point did have a up
to two fold higher risk of later CAD
In ECA study after 13 years those with
depression had 4.5 times higher risk of
developing heart attack. Worse…. even those
with minor depression had same risk.
Ford DE: Arch. Int. Med 1998

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Depression and Ischemic Heart Disease
Mortality: Evidence From the EPIC-Norfolk
United Kingdom Prospective Cohort Study?
 During a total follow-up of 162,974 person-years (the median follow-
up period was 8.5 years), there were 274 deaths from IHD.
 12-month major depression was associated with an increased risk of
IHD mortality (2=13.2, df=1, p=0.0003, after adjustment for age and
sex)
  participants who reported an episode of major depression within 12
months of assessment were 2.7 times more likely to die from IHD
over the 8.5-year follow-up period.
 a trend in association according to recency of major depression, such
that no association was observed for episodes that were experienced
more than 12 months before assessment 
 a stronger association was observed for those who reported three or
more episodes 
 the association was stronger for participants who reported episodes
of major depression that lasted on average 6 months or more

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Can Depression Cause
Diabetes? Meta-analysis
# studies N (est) F/U OR
Knoll 9 173,000 3-16 1.37

Casgrove 11 282,000 3-15.6 1.25

Mezuk 13 6,916 3-15.6 1.60

Findings varies depending on

selection criteria, self report vs.
Knoll et al : Diabetologica 2006
exam, medications used, sample size
Casgrove et al :Occu. Med 2008
Mezuc : Diabetes care 2008

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Can Diabetes Cause
Depression?
Kovacs et al (Diabetes care 1997) followed youths
with DM I for 10 years, 27.5% developed depression
Gavard et al (Diabetes care 1993) did the review of
20 studies and came to conclusion that prevalence
of depression in diabetics range from 8.5% to 27.3%
Anderson et al (Diabetes care 2001) meta-analysis
of 21,351 patients . They found that 11% prevalence
of Major Depression (OR=2.0) among diabetics and
prevalence of clinical relevant depression at 31% in
diabetics.

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Depression and Diabetes
Poor glycemic control
Increased functional disability
Increased cost of care
Poor adherence and control
Increased complications
2.5 times likely to die in 8year f/u study

Gonzales 2008; Edege 2001, Edege 2006; Lustman 2000, Groote, 2001,
Edege 2005

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Obesity and Depression
20 % of obese boys and 30% of girls
have depression
Recent meta-analysis showed
bidirectional increased OR of around 1.5
for both obesity and depression
Often weight loss leads to improvement
in mood, at the same time people who
undergo gastric bypass have higher
rates of depression
Antidepressants are known to cause
weight gain Stunkard : Biol. Psych
2003
Luppino : Arch Gen Psych
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2010
Triad of Death

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Depression and CVA
Depression rates vary from 15-35% but
latest meta-analysis estimates it to be
between 15-20%
L side lesions can cause Depression and R
subcorticle more likely to cause Mania
Depressed patients are 2.5 times likely to
have a CVA in their life time
Diagnosis is difficult
AD, Stimulants and ECT shows effectiveness
One study showed that SSRI can prevent
depression
Evans Biol Psych 2005

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Dementia and Parkinson’s
Disease
Prevalence is 30-50% in Dementia.
Rates depends upon severity, settings
and methods
Prevalence in Parkinson’s 25-40%
Studies show bidirectional effects i.e.
early Depression an independent risk
factor for cognitive decline.
Treatment is difficult due to side effects
and exacerbation of underlying illness
ECT has been used effectively in
Parkinson's and Epilepsy patients

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Depression and Cancer
Likelihood of Depression is 4 times greater and Suicides
rates are twice than that in general population
Depression was unrecognized in 50% of hospitalized
cancer patients
Rates of Depression are higher in pancreatic, ENT and
Breast cancer
Depressed patients followed for 13 years showed higher
incidence of breast cancer but not of other types.
When present for at least 6 years, depression was
associated with a generally increased risk (RR : 1.88) of
cancer in elderly (Penninx, JNCI 1998)
5/10 studies show positive effects of psychotherapy and
survival rates

David Spiegel Biol Psych 2003

Netzel Woman’s Health Psych 2006
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 HIV and Depression
Rates of depression are two times higher
More in female than male
Depression is associated with poor
adherence to treatment and rapid
progression of illness
Depression might even affect HIV entry &
replication increasing the risk for infection
Changes in functioning of Killer
Lymphocytes in depressed patients lead to
delaying of symptoms presentations and
lowering the CD4 count.
Treatments are effective but drug
interactions and changes in antiviral
treatments creates complications
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 Chronic Pain and Depression
30-40 % have Depression
Pain is closely associated with social stress,
monetary gain, personality, and past h/o abuse
These patients are at higher risk for substance
dependence
Fibromyalgia and Depression have comorbidity
of up to 70%
Suicide rates are higher in this population
especially if they have cancer

Fishbain 1997,1999: Ann Med

Lynch 2001 Jr Psych Neuroscience
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Challenges in Diagnosis of
Depression
Inclusive approach
Exclusive approach
Vegetative vs. Psychological symptoms
Scales
Structured Psychiatric Interview
Limitations of DSM IV

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 Depression
How to make a correct Diagnosis
in shortest period of time?

Are you depressed?

Chochinov: Am J Psych 1997
Look for irritability, refusal,
sudden mood changes and
lack of interest
Hopelessness and Suicidality
are not the norms.

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Treatment Issues
Be aware
Do not justify and just put the patients shoes by
thinking “ what if I was in this patient’s situation I
would….”
Ask patient, families, nurses and other care givers
Keep your eyes and ears open for risk factors
Give time empathy and show compassion… it gives
patients opportunity to open up
Yes, It is your job. Depression is part of the severe
medical illness.

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Treatment Principles
Watch for risk factors
Consider current medical conditions,
side effects, Medications, social
situations and finances while considering
an antidepressant
Continue to evaluate as just starting
medications will help in only 40% of cases
Get patient some help through social
services or counseling
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Selection of
Antidepressants
Select AD based on the co-morbidities like OCD, Panics, pain,
Anxiety: Paroxetine, Sertraline, Escitalopram
Wt. Loss: Mirtazepine, TCA, Quetiapine
Wt. Gain/ Fatigue: Buproprion, Fluoxetine, Stimulants
Pain: TCA, Duloxetine
Fatigue, somnolence: Stimulants for short time
Nausea/Vomiting: Mirtazepine, Escitalopram


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 Antidepressants
classification
TCA—amitryptylline,imipramine,triimipramine,dosulupine,nortryptylline etc..

SSRI’s—serrtraline,escitalopram,fluoxetine,fluoxamine,paroxetine,citalopram

SDRI’s—bupropion

SARI’s—trazadone,nefazadone

SNRI’s—venlafaxine,des-venlafaxine,duloxetine,

SSNRI’s—milnacipran

NaSSA—mirtazapine

RIMA—moclobemide,broforomine

MAOI—tranylcypramine,phenelzine

NARI--reboxetine 47
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•Serotonin is released from platelets in response to vascular injury and promotes
vasoconstriction and morphological changes in platelets that lead to Aggregation.

•Serotonin is a relatively weak platelet aggregator on its own:the presence of

epinephrine, collagen and adenosine diphosphate are required for effective clotting.

•Platelets cannot synthesize serotonin – it is taken up by active transport. Selective

serotonin reuptake inhibitors (SSRIs) inhibit the serotonin transporter, which is
responsible for the uptake of serotonin into platelets.

•It might thus be predicted that SSRIs will deplete platelet serotonin, leading to a
reduced ability to form clots and a subsequent increase in the risk of bleeding.

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Hyponatremia and
antidepressants

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Medications that may Cause
Depression

Alcohol
Anticonvulsants .
Barbiturates
Benzodiazepines
Beta-adrenergic blockers
Bromocriptine (Parlodel)
Calcium-channel blockers
Chemotherapeutic agents
Antabuse drugs
Estrogens
Statins
Interferon alfa
Narcotics
Norplant

Culpepper L: J Clin Psych & Primary care

Companion 2005
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Selection of Antidepressants

Drug Interaction: Watch for Cytochrome P 450

More likely: Fluoxetine, Paroxetine and Fluvoxamine
In-between: Sertraline, Citalopram, Duloxetine
Less Likely: Escitalopram, Desvenlafaxine, Buproprion
Risky: TCA and MAOI
Suicidal patients : Do not choose TCA , bring them back
early, give small supply under supervision
Renal Damage: do not choose Desvenlafaxin
Watch out for serotonin syndrome

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Psychosocial Aspects
Spend Time to Know your patients
Make them an informed client and a partner in
treatment
Refer to a therapist for issues like guilt, anger,
poor coping, relationship problems,sucidal
ideation.
Refer to social workers and support services
for help reg: living, home health, job, Insurance
issues, Food stamps.
Watch for family’s mental health and always
ask: “How are you holding/coping it?”
Use humor but wisely.

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Medical Environment
and anxiety
Separated from familiar surroundings
Unfamiliar health care professionals ask a series of personal
questions and perform physical examinations that include
uncomfortable and embarrassing probing of orifices.
Simple issues such as cold rooms can enhance anxiety.
needle phobia appearing when blood is drawn.
sense of confinement causing an anxiety reaction during
imaging studies, phobic reactions and anxiety are quite
common during a medical workup.

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 Contd..
 If a disease is identified during Gnostic process, it is almost always
perceived as a threat (Imboden and Wise 1984). The patient
usually views serious illness as a potential loss. The most basic fear
is loss of life.
 An individual with a myocardial infarction may find his or her career
hopes dashed as a result of the stigma of disease.
 A young mother with breast cancer may fear that she will never
live to see her children fully grown.
 The coronary care unit (CCU) is a specific medical environment
where anxiety can predominate and be a burden to patient
recovery.
 A patient who is very anxious may constantly call a nurse/doctor
shop for reassurance. Anxiety will certainly augment such
“cravings” unless treated.

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Cardiac Disease and
Anxiety
Osler’s descriptions of early-onset angina may
represent the first attempt at defining what we have
come to know as type A behavior (Friedman and
Rosenman 1974).
Another early observer of the heart’s connection to
anxiety was Jacob Mendes DaCosta, who reported on
cardiac symptoms of Civil War soldiers for which he
could not identify objective cardiac findings.
“DaCosta’s syndrome” was further elaborated by Sir
William Lewis (1918) during World War I, when he
coined the term effort syndrome.

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Contd..
Patients with cardiac symptoms such as chest
pain who have no objective cardiac findings on
angiography have a high prevalence (between
43% and 61%) of panic disorder (Beitman et al.
1987; Katon et al. 1988; Zinbarg et al. 1994)
Panic attacks have been demonstrated to impair
myocardial perfusion in patients with cardiac
disease, even when antiarrhythmic cardiac
medication is administered (Fleet et al. 2005).

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Contd..
Other psychophysiological theories have
revolved around the issue of panic disorder
and mitral valve prolapse.
Originally, it was thought that because these
two diseases share similar clinical symptoms,
demographic features, and prevalence within
the general population, the two may be
subsumed within a single classification of
mitral valve prolapse syndrome (Pariser et al.
1978; Savage et al. 1983a; Wooley 1976).

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Medical conditions mimicking or directly resulting
in anxiety
Poor pain control—Such as ischaemic heart disease,
malignant infiltration•
Anaemia
Hypoxia—May be episodic in both asthma and pulmonary
embolus
Hypoglycaemia 
Hypocapnia-May be due to occult bronchial hyperreactivity•
Hyperkalaemia—
Central nervous system disorders (structural or epileptic)
Alcohol or drug withdrawal
Vertigo
Thyrotoxicosis
Hypercapnia
Hyponatraemia
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