Management of

Depression
By:-
Prof. IMTIAZ AHMAD
DOGAR
Psychiatry Department
DHQ Hospital
FSD
Depression Definition:
Depression is a mood disorder
characterized by impaired
functioning at an emotional,
physical, social and even
occupational level.
Low mood
Lack of interest
Lack of pleasure
Decrease activity
Overview of Etiological factors
Psychological
Biological • Stressful life events
• Neurotransmitters • Behavioral factors
• Endocrine system • Cognitive factors
• Family and • Psychodynamic
genetics
• Sleep dysfunction Mood
Woman & mood Disorder
disorders Social
•Support system
•Woman & mood disorders
Neurotransmitters
Low levels of serotonin
associated with depression.
Major Depressive Disorder (MDD) vs
Generalized Anxiety Disorder (GAD)
DSM-IV Criteria

MDD GAD
Depressed mood
Anhedonia Irritability
Change in appetite/weight Sleep disturbances
Insomnia/Hypersomnia Restless/Keyed-up
Psychomotor agitation Easily fatigued
Loss of energy Difficulty concentrating
Guilt/Worthlessness Muscle tension
Diminished concentration
Suicidal ideation

Data from DSM-IV, 2000.

Anxiety/Depression
CONTIUUM
Antidepressants possess the ability to treat both anxiety/depression
Benzodiazepines posses the ability to solely manage depression
Benzodiazepines may exacerbate depression and cognitive impairment
Medical Disorders Associated with
Depression
Cardiac Disease Infectious disease
◦ MI, CHF ◦ Influenza, Mononucleosis
◦ Hepatitis, Syphilis
Malignancy ◦ HIV
◦ Pancreatic carcinoma
◦ Lung and Brain CA Gastrointestinal disease
◦ IBS, Cirrhosis
Neurologic Disease
◦ Parkinson’s disease Endocrine disorders
◦ Stroke ◦ Hypothyroidism, Hyperparathyroidism
◦ Dementia
◦ TBI Pulmonary disease
◦ Sleep Apnea, COPD
◦ MS
Rheumatologic disease
Metabolic Disease ◦ SLE, RA
◦ Electrolyte imbalance ◦ Chronic Fatigue Syndrome
◦ Renal failure
◦ B12 deficiency
◦ Malnutrition
Medications Associated with Depression
Benzodiazepines • Corticosteroids
Alcohol • Methyldopa
Amphetamine • Digitalis
Cocaine • Levodopa
Opiates • Interferon
Estrogen • Reserpine
Metoclopramide • Tamoxifen
Indomethacin • Vincristine
Propranolol • Vinblastine
Cimetadine
 Economic Impact Of Mental
Disorders
High Utilizers Of General Medical Care

• 29% of primary care visits

• 52% of specialty visits
The Top 10% Of
Healthcare Utilizers • 40% of in-hospital days
Account For: • 26% of prescriptions
• >Two-thirds have 1 or more
chronic medical illnesses

Katon et al. Gen Hosp Psychiatry. 1990;12:355.

 Depression Decreases
Adherence
to Medical Regimens
Depression may affect adherence by
◦ Adversely influencing expectations and benefits about efficacy of treatment
◦ Increasing withdrawal and social isolation
◦ Reducing cognitive functioning
and memory
◦ Influencing dietary choices and reducing energy to exercise and follow self-
management regimens (ie, checking blood glucose)
 Co Morbidity
Definition
Any distinct additional entity that has existed or may occur
during the clinical course of a patient who has the index disease
under study 1

Comorbidity can be classified as diagnostic, prognostic, cogent,

non cogent, homotypic, heterotypic, concordant and disordant
2

1. Feinstein AR. Pre-therapeutic classification of co-morbidity in chronic disease. J Chronic Dis.

1970;23(7):455–468.
2. Ann Fam Med. 2009 July; 7(4): 357–363.
Psychiatric comorbidities
Anxiety disorders (particularly panic disorder, obsessive-compulsive
disorder, and posttraumatic stress disorder)
Cognitive disorders (specifically dementia)
Eating disorders
Somatoform disorders
Personality disorders
Sleep disorders (eg, obstructive sleep apnea)
Substance use disorders (the combination of substance use disorders
with a primary psychiatric disorder is sometimes termed "dual
diagnosis")
Screening: Good History a
Must!
Suicide Risk
Psychiatric co-morbidities
Bipolar Disorder
Family history
Past history
Substance Abuse
Prescription Medications
Occult medical illness
 Depression and Diabetes: Comorbidity Facts

1684: T. Willis remarked that diabetes was the result of sadness or prolonged
sorrow 1
Prevalence rate of depression is more than 3 times higher in type 1 diabetes
patients and twice as high in type 2 diabetes patients compared to non
diabetics 2
45% of all diabetes patients suffer with undiagnosed depression 3
Depression was associated with a 60% increase of type 2 diabetes 3

1. Leone T , C oast E , Narayanan S and de G raft AA; Diabetes and depression comorbidity and socioeconomic status in low and middle income countries
(LMIC s): a mapping of the evidence; G lobalization and Health 2012, 8:39: 1 – 10
2. R oy T , Lloyd C E ; E pidemiology of depression and diabetes: A systematic review; J Affect Disord. 2012 O ct;142 Suppl:S8-S21
3. Eged LE , E llis C ; Diabetes and depression: G lobal perspectives; Diabetes R esearch and C linical Practice 87 (2010); 302 – 312.
Depression in women
Women are at a much greater increased risk of
Depression:
◦ At times of hormone swings-premenstrual
◦ 3%-8% of women have Premenstrual Dysphoric Disorder during
reproductive years
◦ Postpartum period
◦ 15-20% of women have depression after delivery
◦ Menopause
◦ Going into puberty
◦ Following a miscarriage (within one month)
Postpartum Depression
15% of women report depression within three months
of delivery
Women with a prior history of depression are at greater
risk
Postpartum “blues” or “baby blues” is normal
◦ mild feeling of being down, tearful
◦ lasts for only a day or so
Skin and Psychiatric Illness
why close association
 Skin is accessible-easy target
of psychiatric illness
 Skin is visible-associated with
self image
 Skin is sensitive-symptoms are
common, varied, source
easily perceived, with a low
threshold for symptoms to
occur
 Depression and Diabetes: Comorbidity Facts

1. Liu Y , Maier M, Hao Y , C hen Y , Q in Y , Huo R ;

2. Factors related to quality of life for patients with type 2 diabetes with or without depressive symptoms - results from a community-based study in C hina. J C lin Nurs. 2012
Nov 8. doi: 10.1111/jocn.120106. C hoi SE , R eed PL; C ontributors to
3. Depressive Symptoms Among Korean Immigrants W ith T ype 2 Diabetes; Nurs R es. 2012 Nov 27 7. Fareeha F et al; Depression and Diabetes in High-R isk U rban P
opulation of P akistan; O pen Diabetes Journal; 2010, V ol. 3, p1-5. 8. G uruprasad,
4. K G , Niranjan, M R and Ashwin S; A Study of Association of Depressive Symptoms among the T ype 2 Diabetic O utpatients Presenting to a T ertiary C are Hospital;
Indian Journal of Psychological Medicine; Jan-Mar2012, V ol. 34 Issue 1, p30-33.
5. 9. Mehdi J et al; Health R elated Q uality of Life in P atients with T ype 2 Diabetes Mellitus in Iran: A National Survey; PLoS O NE 7(8); August 2012, V olume 7, Issue
8 : e44526 10. R oshana M, Azidah AK, Husniati Y L; A Study on Depression among
6. P atient with T ype 2 Diabetes Mellitus in North-E astcoast Malaysia; International Journal of C ollaborative R esearch on Internal Medicine & Public Health (IJC R
IMPH); Aug2012, V ol. 4 Issue 8, p1589-1600.
Depression and Diabetes:
Pathophysiology
Depression and Insulin resistance
◦ Increased inflammation and psychological stress: Increased insulin
resistance and β cell apoptosis
◦ Lifestyle changes: Depression influence lifestyles behaviors such as dietary
intake, exercise and medication adherence which are risk factors for
diabetes development and progression
◦ Suboptimal glycemic control
◦ Higher prevalence of diabetic complications: Including retinopathy,
nephropathy, neuropathy, macrovascular complications and sexual
dysfunctions
◦ High mortality rates

Kan C et al; A systemic review and met analysis of the association between depression and insulin resistance;
Diabetes Care 2013; 36: 480 - 89
Depression: Impact on Diabetes
 Poor glycemic profile 1
 Poor adherence to self care 1
Significantly greater diabetic complications 1
Increased disability, decreased work productivity and quality of
life 1
Greater healthcare service utilization and costs 1
54% greater mortality rates as compared to non depressed 1

1. Egede LE , E llis C ; Diabetes and depression: G lobal perspectives; Diabetes R esearch and C linical Practice 87 (2010); 302 –
312.
Depression Decreases Medication Adherence in
Patients With Diabetes

40
Non Depressed Depressed
27.2 27.9
Nonadherent Days (%)

30
24.5
21.6
18.8 19.3
20

10

0 Oral Lipid Lowering ACE Inhibitors

Hypoglycemic Meds

Lin E et al., Diabetes Care, 2004

 Depression Is Associated With
an Increased Percent of Smoking
20
p<0.001; Major>None
p<0.01; Minor>None
15 N=4225
% Smoking

10
5
0
None Minor Major
Depression Group
Adjusted for demographics, medical comorbidity, diabetes severity,diabetes type and duration, treatment type,
HbA1c and clinic.
Katon et al, Diabetes Care, 2004
 Depression is Associated with an
increased BMI >30 kg/m2 by
80
p<.001; Major>None
70 p<.01; Minor>None
N=4225
B MI > 30 kg/m2 (%)

60
50
40
30
20
10
0
None Minor Major
Depression Group
Adjusted for demographics, medical comorbidity, diabetes severity, diabetes type and duration, treatment type,
HbA1c and clinic
Katon et al, Diabetes Care, 2004
 Depression Is Associated With a Higher
Number of Cardiac Risk Factors

100
90 Non Depressed Depressed
> 3 Cardiac Risk Factors (%)

80
70 62.5 61.3
60
50 38.4
40 35
30
20
10
0
Diabetic Patients With CVD Diabetic Patients Without CVD
N=3010 N=1215

Katon et al, J Gen Intern Med, 2004

Depression and Cardiovascular
diseases
Coexisting depression and cardiovascular diseases will lead the
cause of disability worldwide by 2020 1, 2
Depression and Coronary Artery Diseases (CAD) 3 - 12
◦ Depression increase the risk of recurrent cardiac events and death in patients
with CAD by 3-4 folds

◦ Increase platelet reactivity and inflammatory markers in depression linked to

CAD, congestive heart failure (CHF), atherosclerosis , myocardial infarction (MI)
and stroke

◦ INTERHEART study: Depression for 2 or more week s was strongly associated

with Acute MI

◦ Comorbid depression leads to frequent hospitalization at 6 months after CABG

and recurrent angina during 5 year follow up
 Depression and Cardiovascular
diseases
Depression and MI 1, 2
◦ Prevalence of depression post MI – 10 % to 20 % patients
◦ Risk of cardiac event doubles within 1 to 2 years after an MI in case of untreated
depression in CAD and post MI patients

Depression and Heart Failure (HF) 1

◦ 19.3% to 33.6% patients with HF are diagnosed of clinical depression
◦ Depression in HF patients is associated with increased morbidity and mortality,
higher utility of healthcare resources and increased rates of hospitalization
◦ CAD patients with depression are at more risk to develop HF

Depression and Hypertension 3,4

◦ Prevalence of depression in hypertensive patients was 48.6%
◦ Poor adherence to antihypertensive medications

1. Nieradko BF , Stepnowska M, Piotrowicz R ; E ffect of the dynamics of depression symptoms on outcomes after coronary artery bypass grafting; Kardiologia P olska 2012; 70, 6: 591–597.
2. Laura T ; Depression in C ardiac P atients; U S Pharmacist. 2012;37(11):HS-12-HS-15
3. Bunde J, Martin R . Depression and prehospital delay in the context of myocardial infarction. Psychosom Med. 2006;68:51-57.
4. Araghchian ; M.A. Seif R abie ; F . Zeraati; The Survey of Depression Frequency in Hypertensive P atients; Scientific Journal of Hamadan U niversity of Medical Sciences; Y ear: 2010 V olume:
16 - Issue: 4: 37 – 41
 Depression and Neurological Disorders

Neurological Disorder Prevalence of Depression 1

Parkinson Disease 20 – 45%

Multiple sclerosis 25%
Post - Stroke 30 – 50%
Epilepsy 60%

1. Rickards H; J Neurol Neurosurg Psychiatry 2005;76(Suppl I):i48–i52.

 Depressive Disorders:
Treatment Goals

Treatment

Reduce/Remove Minimize Relapse/

Signs, Symptoms Restore Recurrence Risk
Role/
Function

Adapted from WPA/PTD Educational Program on Depressive Disorders

PHARMACOTHERAPY:
THREE TREATMENT
PHASES

Acute 6–12 weeks

Continuation 4–9 months

Maintenance 1 or more years

 Treatment with
Antidepressant: Acute Phase
Diagnosis

Initiate treatment

Intolerant
Monitor every 1-2 weeks Reduce dose or switch

Assess Week 6

No
Improvement improvement

Adapted from WPA/PTD Educational Program on Depressive Disorders

* Selecting a Safe and Effective
Antidepressant Medication

1) Efficacy

2) Side effect profile relative to your patient’s needs

3) Dosing
All Antidepressants Are
Efficacious
70 - 80% efficacy with any marketed antidepressant
SRI’s are excellent first line choices

TCA’s may be superior for some “severe” depressions

MAO-I’s may be preferred for some atypical depressions
How do antidepressants
work?
Increase the amount of specific neurotransmitters in the nerve synapses.

Edynapram
Antidepressants in Cardiovascular Diseases
(Important Considerations)

SSRIs attenuate platelet activation by depleting serotonin storage and have

been shown to decrease platelet activity in patients with CAD
SSRI use was associated with reduced odds of MI suggesting greater MI
protection with SSRIs
SSRIs with other complementary stress reducing interventions may improve
depression with HF
SSRIs are associated with improved prognosis of post MI and HF patients
SSRIs (Selective
SRIs)
Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
* Serotonin Reuptake Inhibitors: A
First Line Choice for Treatment of
Depression
and Various Anxiety Disorders
Similar efficacy to earlier agents
More acceptable side effect profile
Relative medical safety/ease of use
Reduced lethality with overdose
 Escitalopram : The Drug of Choice
Escitalopram has High selectivity and potency

Dose dependent inhibition of the human serotonin reuptake into

presynaptic nerve terminal

Rapid onset antidepressant action

Cost effective dominating over other SSRIs and Venlafaxine

Garnock J; Escitalopram: A review of its use in the management of major depressive disorder in adults; CNS drugs.. 2010; 24 (9): 769 – 96
 Escitalopram : The Drug of Choice

Escitalopram has greater efficacy in relapse prevention

Predictable tolerability profile with mild to moderate and transient adverse

events

Escitalopram has very low propensity for drug interactions

Escitalopram is only 55% bound to human plasma protein, which makes it

least likely agent for drug – drug interactions by displacement of other highly
protein bound drugs such as Sulfonylureas used in diabetes.

Garnock J; Escitalopram: A review of its use in the management of major depressive disorder in adults; CNS drugs.. 2010; 24 (9): 769 – 96
 Escitalopram: Role in Depression in
Diabetes
Amsterdam JD et al studied the safety and efficacy of Escitalopram in patients
with comorbid depression and diabetes mellitus.

Duration of study: 16 weeks

Escitalopram caused significant reduction in mean HAM – D 17 score
(p<0.001), CGI/S score (p=0.001) and CGI/C score (p=0.001)
Escitalopram produce non significant reduction in the fasting glucose,
fructosamine and glycosylated Hb1Ac levels

HAM – D 17 (Hamilton depression rating 17 questionnaire); CGI/S – Clinical global impression severity scale; CGI/C
– Clinical global impression changes scale
Neuropsychobiology 2006;54:208–214
 Escitalopram: Role in Cardiovascular
diseases
• DECARD Trial (Depression in patients with Acute Coronary
Syndrome) Hansen BH concluded that ….
• Escitalopram significantly prevented the development of
depression in post Acute coronary syndrome (ACS) (p<0.022)
• Escitalopram treatment was safe and well tolerated by patients
with recent ACS during the study duration of one year
• Withdrawal rate due to adverse events was lower with
escitalopram when compared to other antidepressants

Hansen BH et al; Rationale, design and methodology of a double-blind, randomized, placebo-controlled study of escitalopram in prevention of Depression in Acute
Coronary Syndrome (DECARD). Trials. 2009 Apr 7;10:20
 Final Out come
• Depression foreseen as second leading cause of disability by 2020.
• Depression is the common prevalent comorbid conditions with chronic disease
• Presence of depression in diabetes impacts the treatment of diabetes as depressed
diabetic patients have evidence of insulin resistance, poor treatment adherence,
increased diabetes complications and poor quality of life
• Treatment of depression with SSRIs safe in diabetic patients
• Depression is a frequent comorbid condition in cardiovascular conditions and impacts
the outcome of the disease
• Treatment of depression in cardiovascular disease improves the disease prognosis and
prevent recurrences
 Final Out come
• Escitalopram is an approved SSRI for management of Major Depressive
disorder
• Rapid onset of action
• Highly selective and potent
• Effect on glycemic control minimum with better efficacy in treating
comorbid depression
• Effect on reducing Hb1Ac level, no effect on weight and less drug
interactions make it a good choice of treating depression in diabetic patients
Thank You
&
Questions