Depression

● Depression is a common, chronic, and potentially debilitating illness that

has tempered the human condition since the beginning of recorded history.
● Depression is associated with significant functional disability, morbidity and
mortality
● The essential feature of major depressive disorder is a clinical course
characterized by one or more major depressive episodes without a history
of manic or hypomanic episodes.
EPIDEMOLOGY
● Although depression may occur at any age, including early childhood, it is
estimated that the average age of onset of depression is in the mid-20s.

● Some earlier studies found the incidence and prevalence of depression in

women peaking at the age of 35–45 years.

● In bipolar disorder, an earlier age of onset is suggested, perhaps in late

adolescence, with most people experiencing their first episodes before 30
years of age.

ETIOLOGY

1. Genetic cause :

● In depression, one theory suggests that a variant of the gene responsible for
encoding the serotonin transporter protein could account for early
childhood experiences being translated into an increased risk of depression
through stress sensitivity in adulthood
● The incidence of affective disorder in first-degree relatives of someone with
severe depression may be about 20%, which is almost three times the risk
for relatives in control groups
● Evidence of a genetic link has also been found in studies of children from
parents with affective disorder who were adopted by healthy parents.
 ● A higher incidence of affective disorder was found in the biological parents
of adopted children with affective disorder than in the adoptive parents

2) ENVIRONMENTAL FACTORS

● It may be that life events described as ‘threatening’ are more likely to be

associated with depression.
● Employment, higher socio-economic status and the existence of a close and
confiding relationship have been consistently noted to offer some
protection against the development of an episode.

3) BIOCHEMICAL FACTORS
● Biochemical theory of depression postulates a deficiency of
neurotransmitter amines in certain areas of the brain
● Although many neurotransmitters may be implicated, the theory focuses on
an involvement of the neurotransmitters noradrenaline (norepinephrine),
serotonin (5-hydroxytryptamine) and dopamine.

4) ENDOCRINE FACTORS
● The endocrine system, particularly the hypothalamic-pituitary adrenal (HPA)
axis and the hypothalamic-pituitary-thyroid (HPT) axis, is felt to be
implicated in the development of affective disorders
● Some endocrine disorders such as hypothyroidism and Cushing's syndrome
have also been associated with changes in mood.
● People with depression have been found to have increased cortisol levels

5) Physical illness and side effects of medication:

● Disorders of mood, particularly depression, have been associated with
several types of medication and a number of physical illnesses
● An increase in death rates has been found in those patients with co-morbid
depression.
Drugs and physical illnesses implicated in disorders of mood :
DRUGS ILLNESS
Analgesics Viral illness
Antidepressants Carcinoma
Antihypertensives Neurological disorders
Anticonvulsants Diabetes
Opiate withdrawal Multiple sclerosis
Amfetamine withdrawal Thyroid disease
Benzodiazepine withdrawal Addison's disease
Antipsychotics Systemic lupus erythematosus
Benzodiazepines Pernicious anaemia
Antiparkinsonism agents
Steroids
Oral contraceptives

PATHOGENESIS
• Biogenic amine hypothesis: Decreased brain levels of the neurotransmitters
norepinephrine, serotonin (5-HT), and dopamine may cause depression.
• Postsynaptic changes in receptor sensitivity: Studies have demonstrated that
desensitization or downregulation of norepinephrine or 5-HT1A receptors may
relate to onset of antidepressant effects.
• Dysregulation hypothesis: This theory emphasizes a failure of homeostatic
regulation of neurotransmitter systems, rather than absolute increases or
decreases in their activities. Effective antidepressants may restore efficient
regulation.
• 5-HT/norepinephrine link hypothesis: This theory suggests that 5-HT and
norepinephrine activities are linked, and that both the serotonergic and
noradrenergic systems are involved in the antidepressant response.
• The role of dopamine: Several studies suggest that increased dopamine activity
in the mesolimbic pathway contributes to antidepressant activity.
• A disruption of brain derived neurotrophic factor expression in the hippocampus
may be associated with depression
CLINICAL PRESENTATION :
SIGNS AND SYMPTOMS
Emotional symptoms
Physical symptoms
Intellectual or cognitive symptoms
Psychomotor disturbances
DESCRIPTION
diminished ability to experience
pleasure,
loss of interest in usual activities,
sadness, pessimism, crying,
hopelessness, anxiety (present in ~90%
of depressed outpatients),
guilt,
and psychotic features (eg, auditory
hallucinations and delusions)
Chronic fatigue
pain (especially headache),
sleep disturbance,
decreased or increased appetite, loss
of sexual interest, and gastrointestinal
(GI) and cardiovascular complaints
(especially palpitations).
decreased ability to concentrate or
slowed thinking,
poor memory for recent events,
confusion, and
indecisiveness.
psychomotor retardation (slowed
physical movements,
thought processes, and speech) or
psychomotor agitation.
DIAGNOSIS
● Major depressive disorder is characterized by one or more major depressive
episodes, as defined by the Diagnostic and Statistical Manual of Mental
Disorders, 5th ed. :
⮚ Five or more of the following must have been present nearly every
day during the same 2-week period and cause significant distress or
impairment (NOTE: depressed mood or loss of interest or pleasure
must be present in adults [or irritable mood in children and
adolescents]):
1. depressed mood;
2. diminished interest or pleasure in almost all activities;
3. weight loss or gain;
4. insomnia or hypersomnia;
5. psychomotor agitation or retardation;
6. fatigue or loss of energy;
7. feelings of worthlessness or excessive guilt;
8. diminished concentration or indecisiveness;
9. recurrent thoughts of death, suicidal ideation without a specific plan,
suicide attempt, or a plan for committing suicide.
⮚ The depressive episode must not be attributable to physiological
effects of a substance or medical condition.
⮚ Lastly, there must not be a history of manic-like or hypomanic like
episodes unless they were induced by a substance or medical
condition.

● ICD 10 criteria :
ICD 10 diagnostic criteria for a depressive episode
In a depressive episode, the mood varies little from day to day and is often unresponsive to
circumstances, yet may show characteristic diurnal variation as the day goes on. The clinical
picture shows marked individual variations, and atypical presentations are particularly
common in adolescence. In some cases, anxiety, distress and motor agitation may be more
prominent at times than the depression.
For depressive episodes of all grades of severity, a duration of 2 weeks is usually required for
diagnosis, but shorter periods may be reasonable if symptoms are unusually severe and of
rapid onset.
1) Mild depressive episode: For at least 2 weeks, at least two of the usual symptoms of a
depressive episode plus at least two of the common symptoms listed above. An
individual with a mild depressive episode is usually distressed by the symptoms and
has some difficulty in continuing with ordinary work and social activities, but will
probably not cease to function completely.
2) Moderate depressive episode: For at least 2 weeks, at least two or three of the usual
symptoms of a depressive episode plus at least three (preferably four) of the common
symptoms listed above. An individual with moderately severe depressive episode will
have these symptoms to a marked degree, but this is not essential if a particularly
wide variety of symptoms is present overall. They will usually have considerable
difficulties in continuing with social, work or domestic activities.
3) Severe depressive episode: For at least 2 weeks, all three of the usual symptoms of a
depressive episode plus at least four of the common symptoms listed above, some of
which should be of severe intensity

● PATENT ASSESSMENT TOOLS :

1) RATING SCALES
Various rating scales can be used to assist with the assessment of the severity of the disorder.
Two of the more commonly used rating scales are the Beck Depression Inventory and the
Hamilton Depression Rating Scale.
Beck Depression Inventory
This is a self-reporting scale looking at 21 depressive symptoms.
The subject is asked to read a series of statements and mark on a scale of 1–4
how severe their symptoms are.
The higher the score, the more severely depressed a person may be

Hamilton Depression Rating Scale

This rating scale is used by a health care professional at the end of an
interview to rate the severity of depression

● Diagnosis requires a medication review, physical examination, mental status

examination, a complete blood count with differential, thyroid function
tests, and electrolyte determinations.
● Many chronic illnesses and substance abuse and dependence disorders are
associated
with depression. Medications associated with depression include many
antihypertensives, oral contraceptives, isotretinoin, interferon-β1a, and
many others.
● Patient health questionnaire
● MENTAL STATUS EXAM
MANAGEMENT OF DEPRESSION
A) GOALS OF THERAPY
● reduce symptoms of depression,
● minimize adverse effects,
● ensure adherence to the prescribed regimen,
● facilitate return to premorbid functioning,
● and prevent further depressive episodes.
B) NON PHARMACOLOGICAL THERAPY :
● Psychotherapy : Psychotherapy may be first-line therapy for mild
to moderately severe major depressive episode. The efficacy of
psychotherapy and antidepressants is considered to be additive.
Several forms of psychotherapy are available, including
cognitive-behavioral therapy, interpersonal therapy, and
psychoanalytic and psychodynamic therapies, as well as general
supportive counseling techniques, which can serve to promote the
recovery process and decrease the likelihood of future episodes.
● Somatic interventions :
Electroconvulsive therapy (ECT) is a safe and effective treatment
for major depressive disorder. It is considered when a rapid
response is needed, risks of other treatments outweigh potential
benefits, there is history of a poor response to drugs, and the
patient prefers ECT. A rapid therapeutic response (10–14 days) has
been reported.
Repetitive transcranial magnetic stimulation has demonstrated
efficacy and does not require anesthesia as does ECT.
● Lifestyle modifications :
I. Alcohol, recreational drug use, and excessive caffeine
consumption should be minimized
II. Sleep habits should be evaluated and improved to ensure
optimal rest.
 III. Dietary factors should be modified to promote diverse,
balanced, and nutritional eating habits.
IV. Increased physical activity and sustained cardiovascular
exertion can impart a variety of health benefits, including
relief from mood disorders.
V. Other activities may also serve to relieve stress and help
patients acquire insights into their emotional well-being.
These pursuits can range from daily journal writing
(“journaling”), to prayer, meditation, yoga, and tai chi.
VI. Complementary medicines : St. John’s wort (hypericum
pertforetum), S-Adenosyl-L Methionine, omefa 3 fatty acid,
folate

C) THERAPEUTIC INTERVENTIONS :

Drug class Examples

Selective Serotonin Reuptake Inhibitors Citalopram

(SSRIs) Escitalopram
Fluoxetine
Paroxetine
Sertraline

Serotonin–Norepinephrine Reuptake
Inhibitors (SNRIs)
Newer-generation SNRIs Desvenlafaxine
Duloxetine
Venlafaxine

Tricyclic antidepressants (TCAs) Amitriptyline

Desipramine
Imipramine
 Nortriptyline

Norepinephrine and Dopamine Bupropion

Reuptake Inhibitor (NDRI)

Mixed Serotonergic Effects (Mixed Nefazodone

5-HT) Trazodone
Vilazodone

Serotonin and α2 -Adrenergic Mirtazapine

Antagonist

Monoamine Oxidase Inhibitors Phenelzine

(MAOIs) Selegiline
Tranylcypromine
Moclobemide
Isocarbazide

Inhibition of phospholipase C Lithium carbonate

D)Treatment algorithm for management of uncomplicated

depression
Dosing regimens
Drug Brand Name Initial Dose Maximum Usual
(mg/day) Dose Dosage
(mg/day) (mg/day)
Fluoxetine Prozac 10 80 10-20
Sertraline Zoloft 25 200 50
Paroxetine Paxil 10 50 10-20
Citalopram Celexa 10 60 20
Escitalopram Lexapro 5 20 10
Duloxetine Cymbalta 30 120 60
Amitriptyline Elavil 25 100 100-300
Treatment of depression in special population :
SPECIAL TREATMENT
POPULATION
Elderly Patients • In the elderly, depressed mood may be less prominent than other
symptoms, such as loss of appetite, cognitive impairment,
sleeplessness, fatigue, physical complaints, and loss of interest and
enjoyment in usual activities
• The SSRIs are often considered first-choice antidepressants in
elderly patients.
• Bupropion, venlafaxine, and mirtazapine are also effective and well
tolerated.
Pediatric Patients • Symptoms of depression in childhood include boredom, anxiety,
failing adjustment, and sleep disturbance.
 • Data supporting efficacy of antidepressants in children and
adolescents are sparse. Fluoxetine is the only FDA approved
antidepressant for treating depression in patients below 18 years of
age.
Pregnancy The risk for depression is elevated during pregnancy and during the
postpartum period
Fetal malformations have been rarely reported with TCAs and they
are generally regarded as safe in pregnant women. MAOIs, however,
should be avoided due to increased risks for hypertensive crises.
Relative Resistance The STAR*D study showed that one in three depressed patients who
and did not achieve remission with an antidepressant became
Treatment-Resistant symptom-free when an additional medication (eg, sustained-release
Depression bupropion) was added, and one in four achieved remission after
switching to a different antidepressant (eg, extended-release
venlafaxine).
Alternatively, the current antidepressant may be augmented
(potentiated) by addition of another agent (eg, lithium or
triiodothyronine [T3 ]), or another antidepressant can be added. An
atypical antipsychotic can be used to augment antidepressant
response

MONITORING PARAMETERS
DRUG Adverse effects Monitoring parameters

Common to all Suicidality Behavioral changes

ATDs Mental status
Common to all Anxiety or nervousness Assess severity and impact on patient
SSRIs and SNRIs functioning and quality of life
Insomnia Sleep patterns
Nausea Frequency and severity
Serotonin syndrome Autonomic function (eg, pulse,
temperature); neuromuscular function
SSRI specific :
Citalopram QT interval Electrocardiogram; electrolytes (eg,
prolongation potassium, magnesium)
Fluoxetine Anorexia Weight (over time)
Paroxetine Anticholinergic effects Symptoms: dry mouth, constipation,
urinary retention, mental status
SNRI-Specific:
Duloxetine Orthostatic
hypo-tension Blood pressure, pulse
Venlafaxine Dose-related
hyper-tension Blood pressure, pulse
Mixed Serotonergic
Effects (Mixed
5-HT): Liver toxicity Liver function tests
Nefazodone Orthostatic hypotension
Trazodone Blood pressure, pulse

Serotonin and α2
-Adrenergic
Antagonist:
Mirtazapine Weight gain Body weight
Norepinephrine
and Dopamine
Reuptake Inhibitor
(NDRI) : Bupropion Seizure activity Electroencephalogram