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

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 2183% in primary care practices In the CURES study conducted at chennai, 25,455 subjects participated in this study.

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.
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The global burden of disease, 19902020

Lower Respiratory Heart Diseases
Depression Traffic accidents

Infections Diarrheal Diseases Perinatal conditions Depression Heart Diseases Cerebrovascular D/O

Cerebrovascular D/O
COPD Lower Respiratory

Infections

Lopez et al :Global burden of disease and risk factors, Oxford University Press, New York (2006)

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

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Likelihood of Depression Increases with No. of Physical Symptoms at Presentation

70 60 50 40 Series1 30 20 10 0 0-1 2 to 3 4 to 5 6 to 8 >9 No. of Physical Symptoms

Depression Likelihood /Percentage

Kroenke K, et al. Arch Fam Med 1994

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Prevalence of Psychiatric 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 Musculo skeletal Respiratory Heart Upper GI Neurological Endocrine

were evaluated for General Medical Conditions Total prevalence was 53% Those with older age, Lower income, unemployment, limited education and longer duration of depression were at higher risk
Yates et al, Gen Hosp Psych 2004 STAR-D Study

Prevalence % 43% 32% 29% 26% 25% 24%

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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

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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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Depression: 1-Year Mortality in Nursing Home Patients

70 60 Deaths (%) 50 40 47.4%

29.8%

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20 10 0 Depressive Disorder n = 57 No Depressive Disorder 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 followup 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
Casgrove Mezuk

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11 13

173,000
282,000 6,916

3-16
3-15.6 3-15.6

1.37
1.25 1.60

Findings varies depending on selection criteria, self report vs. exam, medications used, sample size

Knoll et al : Diabetologica 2006 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 2010
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Triad of Death
Diabetes

Depression

CAD
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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 Parkinsons Disease

Prevalence is 30-50% in Dementia. Rates depends upon severity, settings and methods Prevalence in Parkinsons 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 Womans 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 complications

antiviral

treatments

creates

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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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Challenges in Diagnosis of 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 patients 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
TCAamitryptylline,imipramine,triimipramine,dosulupine,nortryptylline etc..

SSRIsserrtraline,escitalopram,fluoxetine,fluoxamine,paroxetine,citalopram
SDRIsbupropion SARIstrazadone,nefazadone SNRIsvenlafaxine,des-venlafaxine,duloxetine, SSNRIsmilnacipran NaSSAmirtazapine RIMAmoclobemide,broforomine MAOItranylcypramine,phenelzine

NARI--reboxetine

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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 familys 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

Oslers

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 hearts 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. DaCostas 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 controlSuch as ischaemic heart disease, malignant

infiltration Anaemia HypoxiaMay 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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