Outlines

I am depressed

What is depression?
Epidemiology of depression
Neurobiology of depression
Diagnosing depression

Wai-chi Chan
Department of Psychiatry
LKS Faculty of Medicine
The University of Hong Kong

Take Home Messages

Depression is a biological disorder
Depression is an illness, not a weakness
Active research on numerous mechanisms
Depression can be secondary
Many drugs are available to treat depression
Psychotherapies are important treatments
Treat the patient biopsychosocially

Treating depression
Interacting with the patient
Questions and Answers

Depression!
I feel:
upset
bad
blue
trashed
terrible
down
sad
depressed

Keep the patient safe!

What is depression?
Not simply mood fluctuation or feeling down
A clinical syndrome
There are physical / biological symptoms
Note the neuroscientific basis
Diagnostic criteria exist

Epidemiology
Lifetime prevalence of 15 percent
More in female (up to 25%)
Mean age of onset about 20 to 30
Concordance rate in monozygotic twins is 50%
Costs $85 billion HKD yearly for lost of productivity
Fourth leading cause of disability worldwide

Come on, dont think about it is not a cure!

Depression increases morbidity

For example, depression in late life is associated with
Weight loss
Chronic medical illnesses (e.g. cardiovascular disease,
bone mineral density)
Poor self-perceived health
Functional impairment

Depression increases mortality

Depression increases non-suicide mortality

RR = 1.2 4.0
Possible mediators
Behavioural risk factors (e.g. poor adherence to treatment,
inactivity, alcohol consumption)

Cognitive impairment

Biological risk factors (e.g. altered thrombogenesis)

Possible mechanisms: poor appetite -> low BMI -> frailty, 5-

Subclinical disease / prevalent disease (e.g. cardiovascular

HTTLPR polymorphism, inflammatory activity, etc.

Neurobiology of Depression

disease)

Hypotheses for Depression (1)

Hippocrates (460-357 B.C.)
Melancholia emerges when environmental influences, such
as planet alignment, cause the spleen to secrete black bile,
which darkens the mood.

Burton (1621)
Depressed people are often born of melancholy parents

Kraepelin (1856-1926)
Detected a genetic contribution to manic-depressive illness

Meyer (1866-1950)
Coined the term psychobiology; depression was due to
biological and environmental factors combined

Hypotheses for Depression (2)

Bunney and Davis (1965)
Biogenic amine hypothesis depression was caused by a
deficiency in brain concentration or receptor function of NE,
dopamine, and 5-HT

Carroll and Davies (1970)

Hypothalamic-pituitary-adrenal / -thyroid axes correlation to
depression

Janowsky et al. (1972)

Cholinergic activity relative to NE activity is associated with
mood disorders

Neurobiology of Depression (1)

Functional and structural changes
activities in ventromedial prefrontal cortex
sensitivity to pain, anxiety, depressive ruminations, tension

activities in dorsolateral prefrontal cortex

Psychomotor retardation, apathy, deficits in attention and working
memory

connectivity between amygdala and ant cingulate cortex

ACC fails to serve its inhibitory role in emotional regulation

hippocampal volume
Predisposing factor for depression
Changes also accumulates in the course of the disease

Neurobiology of Depression (2)

Neurochemical / hormonal changes
cortisol, CRH
proinflammatory cytokines
BDNF
5-HT neurotransmission
NA neurotransmission

Diagnosing Depression

Brain-Derived Neurotrophic Factor

May be a downstream target of drugs

Has antidepressant-like effect
Protects against neuronal damage
Decreased level in depressed patients
Stress cortisol BDNF gene suppressed
May explain treatment time lag?

ICD-10 Depressive Disorders

F32 Depressive episode
F32.0 Mild depressive episode
.00 Without somatic syndrome
.01 With somatic syndrome

F32.1 Moderate depressive episode

.10 Without somatic syndrome
.11 With somatic syndrome

F32.2 Severe depressive episode without

psychotic symptoms
F32.3 Severe depressive episode with psychotic
symptoms

ICD-10 Depressive Disorders

F32 Depressive episode (continued)
F32.8 Other depressive episodes
F32.9 Depressive episode, unspecified

F33 Recurrent depressive disorder

F34 Persistent mood [affective] disorders
F34.1 Dysthymia

Depressive Episode
At least 2 of the following 3 must be present
Depressed mood most of the day, nearly daily
Loss of interest
Decreased energy

A total of at least 4 additional symptoms

Loss of confidence or self esteem
Feelings of self-reproach or inappropriate guilt
Recurrent suicidal ideation or any suicidal behaviour
Decreased ability to think or concentrate
Psychomotor agitation or retardation
Sleep disturbance
Appetite change

Last for at least 2 weeks; not due to substance use

or organic mental disorders

Iatrogenic Depression

Causes of Secondary Depression

Head trauma
Infection
CVA, CHF, MI
Metabolic disturbance
Thyroid or glucocorticoid disturbance
Vitamin deficiency
Multiple sclerosis, neurodegeneration
Drug intoxication or withdrawal
Drugs

Pharmacotherapy

Cardiac and antihypertensive drugs

Sedatives
Stimulants and appetite suppressants
Steroids
Antibiotics
Analgesics and antiinflammatory drugs
Antineoplastic agents

Pharmacological treatment
There is no ideal antidepressant
All are associated with problems though some
are better tolerated
Choice is determined by individual clinical
circumstances, particularly co-morbid physical
illnesses and medications

Antidepressants
Monoamine Oxidase Inhibitors (MAO-I)
Tri- and Tetra-cyclic antidepressants (TCA)
Selective 5-HT Receptor Inhibitors (SSRI)
Selective 5-HT Norepinephrine Receptors
Inhibitors (SNRI)

TCA
Amitriptyline, nortriptyline
Adverse effects: sedation, often with hangover,
postural hypotension, tachycardia, arrhythmia,
dry mouth, blurred vision, constipation, urinary
retention
Nortriptyline less sedative / anticholinergic /
hypotensive

Others

They are not happy pills!

Reversible Inhibitor MAO-A

(RIMA)
Moclobemide (Aurorix)
Adverse effects: insomnia, nausea, agitation,
confusion
Hypertension reported
Food interaction possible if high doses
(>600mg/day) used or if large quantities of
tyramine ingested

SSRIs
Adverse effects: nausea, vomiting, dyspepsia,
abdominal pain, diarrhoea, rash, sweating,
agitation, anxiety, headache, insomnia, tremor,
sexual dysfunction, hyponatraemia
Discontinuation symptoms may occur

Other antidepressants (2)

Mirtazapine (Remeron)
NaSSA
Adverse effects: increase appetite, weight gain,
drowsiness, oedema, dizziness, headache,
blood dyscrasia
Nausea and sexual dysfunction relatively
uncommon

Selective Serotonin Reuptake

Inhibitors (SSRIs)
Citalopram, Escitalopram, Sertraline, Paroxetine,
Fluoxetine, Fluvoxamine

Other antidepressants (1)

Tetracyclic (Mianserin)
Sedation, rash, blood dyscrasia, jaundice

Bicyclic (Trazodone)
Sedation, dizziness, headache, nausea,
vomiting, postural hypotension, priapism

Other antidepressants (3)

Venlafaxine (Efexor)
SNRI
Adverse effects: nausea, insomnia, dry mouth,
somnolence, dizziness, sweating, nervousness,
sexual dysfunction, headache
BP at higher doses
Discontinuation symptoms common

Other antidepressants (4)

Duloxetine (Cymbalta)
SNRI
Adverse effects: nausea, insomnia, headache,
dizziness, dry mouth, somnolence, constipation,
anorexia, small increase in heart rate & BP

Other antidepressants (5)

Bupropion (Wellbutrin)
DRI
Apathetic geriatric depression - activating
Adverse effects: headache, insomnia, agitation,
dizziness, tremor, weight loss, tachycardia, dry
mouth

Other antidepressants (6)

Agomelatine (Valdoxan)
M1/M2 melatonin agonist + 5HT2c antagonist
Improve subjective sleep quality & normalise
sleep-wake rhythm
Adverse effects: sexual S/E rare
LFT monitoring

Pharmacokinetic DDIs
Drug A alters the level of Drug B
One drug changes the level of another
or absorption
or hepatic metabolism
or renal elimination

Drug-Drug Interactions

Pharmacokinetic DDIs:
Altered metabolism
Cytochrome P 450 (CYP 450)
accounts for majority of drug metabolism

Main isoforms:
CYP 1A2
CYP 2C9
CYP 2C19
CYP 2D6
CYP 2E1
CYP 3A4

CYP 2C9

CYP 1A2
Examples of
Substrates

Inhibitors

Caffeine
Theophylline

Examples of
Inducers

Substrates

Inhibitors

Inducers

Ciprofloxacin

Smoking

Glyburide

Sulfamethoxazole

Carbamazepine

Fluvoxamine

Charbroiling

Warfarin

Trimethoprim
Metronidazole

Rifampin

Duloxetine
Agomelatine
Many TCAs

Cabbage

Fluoxetine
Fluvoxamine

CYP 2C19

CYP 2D6
Examples of

Examples of
Substrates

Inhibitors

Inducers

Phenytoin

PPIs

Rifampin

Tertiary TCAs
Citalopram

Fluoxetine
Fluvoxamine
Moclobemide

Electroconvulsive Therapy

Substrates

Inhibitors

Inducers

Codeine
Metoprolol

Quinidine
Ritonavir

n/a

Desipramine
Venlafaxine
Trazodone
TCA

Bupropion
Paroxetine
Fluoxetine
Duloxetine
Escitalopram

Psychotherapy

No absolute contraindication
For the very depressed, psychotic, suicidal
patients
Also for manic and schizophrenic patients
Need pretreatment evaluation
Use of atropine, methohexital &
succinylcholine
Bilateral vs. unilateral electrode placements
Side effects:
Anterograde memory loss
Headache
Muscle pain
Broken teeth
(fatality 0.01% for each patient)

Different Approaches

Psychodynamic approach
Cognitive (behavioural) approach
Interpersonal approach
Integrative approach
Family approach
Group approach

Patient selection and depression type affect outcome

Cognitive Behavioural Therapy

Focuses on cognitive distortions
The thought, emotion, behaviour triangle
Addressing maladaptive patterns
Homework is important
Equal in efficacy and fewer
side effects
Combined drug and CBT for
severe depression

Interpersonal Therapy

Patient Contact

Medical model of depression

Interpersonal problems have early roots

Be empathic; not patients fault

Three treatment phases

Establish therapeutic alliance

Four areas of focus:

Assess symptoms and co-morbidities

Unresolved grief

Assess safety issues (e.g. suicidality)

Social role dispute

Formulate

Social role transitions

Establish treatment plan

Interpersonal deficits

Have adequate follow-ups

References

Summary
Depression is biological
Depression is very curable
Encourage early treatment
Many treatment strategies
Depression is an illness, not a weakness!
Everyone deserves to be happy!

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