Dr.

Sydney Moirangthem
Asst. Prof, Dept. of Psychiatry
NIMHANS

Mood - a pervasive and sustained feeling tone

that is experienced internally and that influences
a person's behavior and perception of the world.

Affect - the external expression of mood.

Mood - Normal, elevated, or depressed.

Healthy persons experience a wide range of

moods and have an equally large repertoire of
affective expressions; they feel in control of their
moods and affects.

Mood disorders one of the most common illnesses of

humankind for the past 2500years.

Depression - fourth in a list of the most urgent health

problems worldwide & by 2030 will over take all other
diseases to top the list (WHO).

Afflict one out of five women and one out of ten men
at some time during their lives.

Many persons with mood disorders are disabled, and

rates of suicide are high in young and, particularly,
elderly men.

Although depressive disorders are more common in

women, more men than women die of suicide.

The Old Testament story of King Saul describes a

depressive syndrome.

About 400 BC, Hippocrates used the terms mania

and melancholia to describe mental disturbances.

Celsus - described melancholia (from Greek melan

[black] and chole [bile]) in his work De re medicina
as a depression caused by black bile.

In 1899, Emil Kraepelin described the manicdepressive psychosis; also described a depression
that came to be known as involutional
melancholia.

Incidence & prevalence: The highest

lifetime prevalence (almost 17 %) of any
psychiatric disorder.
The yearly incidence of a major depression is
1.59 percent (women, 1.89 percent; men,
1.10 percent).
Sex: twofold greater prevalence of major
depressive disorder in women than in men.
Age: The mean age of onset - 40 years; with
50 percent of all patients having an onset
between the ages of 20 and 50.
Major depressive disorder can also begin in
childhood or in old age.

The monoaminergic systems are now believed to

be involved.
Biogenic Amines: Norepinephrine (NE) and
Serotonin (5-HT) are the two neurotransmitters
most implicated in the pathophysiology of mood
disorders.

NE:
1. Downregulation or decreased sensitivity of 2adrenergic receptors.
2. Activation of pre-synaptic 2-adrenergic receptors
results in a decrease of the amount of
norepinephrine released.
3. Presynaptic
2-receptors are also located on
serotonergic neurons and regulate the amount of
serotonin released.

5 HT:

1.

Serotonin
has
become
the
biogenic
amine
neurotransmitter most commonly associated with
depression.
Depletion of serotonin may precipitate depression.
Some patients with suicidal impulses have low
cerebrospinal fluid (CSF) concentrations of serotonin
metabolites and low concentrations of serotonin uptake
sites on platelets.

2.
3.

Dopamine (DA):

1.

Dopamine activity may be reduced in depression and

increased in mania.
The
mesolimbic
dopamine
pathway
may
be
dysfunctional in depression & the dopamine D 1 receptor
may be hypoactive in depression

2.

Endocrine changes:

1.

Blunted prolactin and growth hormone (GH) responses to

tryptophan/citalopram (5HT system), blunted GH responses to
clonidine (NA system) and apomorphine (DA system),
increased GH response to physostigmine (ACh system) suggest
reduced monoamine functioning and increased cholinergic
functioning in depression.

2.

Increased cortisol seen in -50% of patients (particularly

endogenous subtype), & is associated with adrenal
hypertrophy.

3.

Approximately 5 to 10 percent of people evaluated

for depression have previously undetected thyroid
dysfunction, as reflected by an elevated basal
thyroid-stimulating hormone (TSH) level.

Changes in sleep pattern: Reduced total

SWS and shortened REM latency (secondary to
increased
cholinergic
and/or
reduced
serotonergic/ noradrenergic drive.
Genetic factors:

1.

Appear to influence the risk of depression by altering

individual sensitivity to the effects of life stressors.

2.

Linkage analysis suggests an association between

the
serotonin
transporter
gene,
depression,
treatment
response,
and,
possibly,
suicidal
behaviour.

Life Events and Environmental Stress:

1.

2.

Stressful life events more often precede first, rather

than subsequent, episodes of mood disorders.
Disruption of normal social, marital, parental, or
familial relationships is correlated with high rates of
depression, and are risk factors to recurrence.

Personality Factors:

1.

No single personality trait or type uniquely predisposes

a person to depression.
Persons with certain personality disorders - OCPD,
histrionic, and borderline may be at greater risk for
depression than persons with antisocial or paranoid
personality disorder.

2.

Diagnosis: ICD - 10
Typical symptoms:
1. Sadness - Depressed
mood,

2. Anhedonia

- Loss of
interest
and
enjoyment, and
- Reduced
energy leading to
increased
fatiguability
and
diminished activity.

The
above
symptoms
must be:

Present for at least 2

weeks and represent
a change from normal.

Are not secondary

to
the
effects
of
drug/alcohol
misuse,
medication, a medical
disorder,
or
bereavement.

May cause significant

distress
and/or
impairment of social,
occupational,
or
general functioning.

3. Anergia

Core symptoms:

Somatic symptoms:

1.

Reduced concentration and

attention.
Reduced self-esteem and
self-confidence.
Ideas
of
guilt
and
unworthiness (even in a
mild type of episode).
Bleak and pessimistic views
of the future.
Ideas or acts of self-harm or
suicide.
Disturbed sleep.
Diminished appetite.

1.

Loss of emotional reactivity.

Diurnal mood variation.
Anhedonia.
Early morning wakening.
Psychomotor agitation or
retardation.
Loss
of
appetite
and
weight.
Loss of libido.

2.

3.

4.

5.

6.
7.

2.
3.
4.
5.

6.

7.

Psychotic symptoms/features:

1. Delusions

e.g. poverty; personal inadequacy; guilt

over presumed misdeeds; responsibility for world
events:
accidents,
natural
disasters,
war;
deserving of punishment; other nihilistic delusions.

2. Hallucinations

e.g. auditory: defamatory or

accusatory voices, cries for help or screaming;
olfactory: bad smells such as rotting food, faeces,
decomposing flesh; visual: tormentors, demons,
the Devil, dead bodies, scenes of death or torture.

3. Catatonic

symptoms or marked psychomotor

retardation (depressive stupor).

Mild: 2 typical symptoms & 2 other core symptoms.

Moderate: 2 typical symptoms & 3+ other core
symptoms.
Severe: 3 typical symptoms & 4+ other core
symptoms

History.
Mental Status Examination.
Physical examination.
Investigations.

History: Key areas of enquiry include:

Any clear psychosocial precipitants,

2. Current social situation,
3. Use of drugs / alcohol,
4. Past history of previous mood symptoms (including
subclinical periods of low or elevated mood,
previous Deliberate Self Harm (DSH) / suicide
attempts),
5. Previous effective treatments,
6. Premorbid personality,
7. Family history of mood disorder,
8. Physical illnesses,
9. Current medication.
1.

Mental Status Examination :

Focused enquiry about subjective mood
symptoms, somatic symptoms, psychotic
symptoms, symptoms of anxiety, thoughts of
suicide.
Objective assessment of psychomotor
retardation/agitation, evidence of DSH, cognitive
functioning (MMSE).

Physical examination: Focused on possible

differential diagnoses .

Investigations:

1. Standard

tests: CBC, ESR, B12/folate, U&Es,

LFTs, TFTs, glucose, Ca2+ .

2. Focused

investigations (if indicated by history

or physical signs)
Urine toxicology
Thyroid antibodies
Antinuclear antibody
Syphilis serology
CT/MRI, EEG, LP (VDRL, Lyme antibody, cell count,
chemistry, protein electrophoresis)
HIV testing
Dexamethasone suppression test (Cushing's disease)
Cosyntropin stimulation test (Addison's disease)

Non-Pharmacological Treatment (Psychological

therapies):
1. Influenced by the severity of the depressive episode
(usually for mild-moderate cases),
2. Local availability, and
3. Patient preference.
4. Medication alone can effectively relieve symptoms
but combination therapy is usually better.
5. Types:
Cognitive & Behavioral Therapy.
Interpersonal Therapy.
Duration: usually 8-12weeks in mild to moderate
cases.

Pharmacological Treatment:
Choice of antidepressant
1. Guided by anticipated safety and tolerability,
2. Physician familiarity (which allows for better
patient education in anticipation of adverse
effects),
3. Presenting symptoms, and
4. History of prior treatments

Regular Follow-Up frequent initially (1-4 wks; to

monitor treatment response and assess for any
unwanted side-effects) & spaced accordingly.

Generic Name

Usual Daily Dose

Side-Effects

Norepinephrine (NE) Reuptake Inhibitors

75-300mg.

Drowsiness, Insomnia,
Ortho static
Hypotension,
agitation, Cardiac
Arrhythmias, Weight
gain, Anticholinergic
SE: dry mouth,
blurred vision, urinary
hesitancy, and
constipation.

Nortriptyline (TCA)

40-200mg.

-do-

Maprotiline

100-225mg.

-do-

Desipramine (TCA)

Dopamine Reuptake Inhibitor

Bupropion

200-400mg.

Insomnia or agitation,
GI distress

Generic Name

Usual Daily Dose

Side-Effects

Selective Serotonine (5-HT) Reuptake Inhibitors

Escitalopram

10-20mg.

All SSRIs may cause

insomnia, agitation,
sedation, GI distress,
and sexual
dysfunction; increased
suicide rate is
reported.

Fluoxetine

10-40mg.

-do-

Fluvoxamine

100-300mg.

-do-

Paroxetine

20-50mg.

-do-

Sertraline

50-150mg.

-do-

Pre- and Postsynaptic Active Agents

Nefazodone
Mirtazapine

300-600mg.

Sedation.

15-30mg.

Sedation & weight gain

(devoid of sexual
dysfunctions)

Generic Name

Usual Daily Dose

Side-Effects

NE and 5-HT Reuptake Inhibitors

Drowsiness, Insomnia,
Ortho static
Hypotension, agitation,
Cardiac Arrhythmias,
Weight gain,
Anticholinergic SE: dry
mouth, blurred vision,
urinary hesitancy, and
constipation.

Amitriptyline (TCA)

75-300mg.

Imipramine (TCA)

75-300mg.

-do-

Venlafaxine

75-375mg.

Sleep changes, GI
distress,
discontinuation
syndrome;
hypertension in higher
doses.

Duloxetine

30-60mg.

-do-

Antipsychotics: if psychotic symptoms or

aggression/irritability are present.
Second-line Drugs: Lithium, Carbamazepine,
Divalproate, Thyroxine

First-line therapy when there are severe biological

features (e.g. significant weight loss/reduced
appetite) or marked psychomotor retardation.
Suicidal or aggressive patients.
Prominent Psychotic features are present.

Transcranial magnetic stimulation

(TMS):
investigational treatment of
depression that has been shown to have
efficacy in several controlled trials.

Vagus nerve stimulation (VNS): recently

approved
for
treatment-resistant
depression, but its degree of efficacy is
controversial. Stimulates the left vagus.

Depression may occur at any age, although late onset depression

may be milder, more chronic, more likely to be associated with
life events, and more likely to have a sub-clinical prodrome.
Depressive episodes vary from 4-30 wks for mild-moderate cases,
to an average of about 6 mths for severe cases (25% will last up
to 1 yr).
Episodes of recurrent depression tend to be shorter (4-16 wks).
10-20% of patients will have a chronic course, with persistent
symptoms lasting over 2 yrs.
The majority of patients experiencing a depressive episode will
have further episodes later in life (risk of recurrence is -30% at 10
yrs, -60% at 20 yrs).
Risk of recurrence is greater when there are residual symptoms
after remission (about a third of cases)e.g. low mood, anxiety,
sleep disturbance, reduced libido, and physical symptoms
(headache, fatigue, GI upset).

Suicide rates for severe depressive episodes vary but may be

up to 13% (i.e. up to 20 times more likely than the general
population), with a slightly higher rate for those who have
required hospital admission (12-19%).
The overall death rate for patients with depression is higher
than the general population (SMR 1.37-2.49) with the cause of
death usually due to suicide, drug and alcohol problems,
accidents, cardiovascular disease, respiratory infections, and
thyroid disorders.

Good outcome:
Acute onset, endogenous depression,
earlier age of onset.
Poor outcome: Insidious onset, neurotic depression, elderly,
residual symptoms, neuroticism, low self-confidence,
comorbidity (alcohol or drug problems, personality disorders,
physical illness), lack of social supports.