Treatment of Depression

Question 1

MDD

Answer 1

Major Depressive Disorder

Question 2

Diagnosis of MDD

Answer 2

• at least 5 out of 9 symptoms (In.S.A.D.C.A.G.E.S)
• must have In & D
• for most of the same 2 week period
• causing significant distress or functional impairment
• symptoms are not drug-induced / secondary to other medical conditions

Question 3

Goal of therapy

Answer 3

1. Hamilton Rating Scale =< 7
2. Remission of symptoms / symptoms free
3. Treatment adherence
4. Suicide prevention

Question 4

Non-pharmacological therapy (4)

Answer 4

1. Sleep hygiene
2. Psychotherapy
   - cannot monotherapy in moderate-severe MDD
3. Electroconvulsive Treatment (ECT) (more severe & refractory MDD)
4. Repetitive Transcranial Magnetic Stimulation (rTMS) (less invasive)

Question 5

Pharmacological therapy + Adjunctives

Answer 5

1. Anti-depressants
   - SSRI, SNRI, Mirtazapine (NaSSA) & Bupropion
   > Agomelatine & Vortioxetine
   > TCA
   > MAOi
2. Adjunctive medications
   - anxiolytics
   - hypnotics
   - short course, PRN
   - only if needed

Question 6

Duration of antidepressant treatment

Answer 6

Acute phase
- 4-8 weeks (max 12 weeks)

Continuation phase
- 4-9 months

Total duration : at least 6-12 months

Question 7

Duration for physical symptoms treatment (eg poor sleep)

Answer 7

1-2 weeks

Question 8

Duration for mood symptoms treatment

Answer 8

> 6 weeks

• due to downregulation of pre-synaptic autoreceptors to prevent negative feedback regulation of neurotransmitter secretion into synaptic space
• leads to disinhibition & promotion of neurotransmitter release

Question 9

Efficacy among antidepressants

Answer 9

All have similar efficacy for uncomplicated first episode of MDD

Question 10

Duloxetine

Answer 10

SNRI

Also indicated for :

• diabetic peripheral neuropathy
• fibromyalgia
• chronic musculoskeletal pain

Question 11

All serotonergic agents (SSRI, SSRI, TCA, SMS) ADR

Answer 11

1. GI effects

2. SD

Question 12

Venlafaxine ADR

Answer 12

• worsens HTN

Question 13

Mirtazapine ADR

Answer 13

• sedation

- weight gain (due to increased appetite)

Question 14

Mirtazapine benefit

Answer 14

Reduce SD

Question 15

Bupropion CI

Answer 15

• history of seizures
• psychosis
• eating disorders

Question 16

Bupropion benefit

Answer 16

No SD effect cos NDRI (no serotonergic effects)

Question 17

TCAs ADR (6)

Answer 17

1. Anticholinergic (dry mouth, blurred vision, constipation)
2. Sedation
3. Orthostatic hypotension
4. Arrhythmias
5. Seizures
6. Fatal on overdose

Question 18

Counselling point for all antidepressants to =<24y/o

Answer 18

Suicidality association

Question 19

Minimal CYP interactions (5)

Answer 19

MEVDV

1. Mirtazapine
2. Escitalopram
3. Venlafaxine
4. Desvenlafaxine
5. Vortioxetine

Question 20

Significant PD interactions

Answer 20

1. Serotonin Syndrome (RDTSMCCD)
   - multiple serotonergic agents used tgt
2. CNS depression

Question 21

Discontinuation of antidepressant

Answer 21

• taper dose gradually over 4 weeks
• 10-25% every 1-2 weeks
• if used daily for >=2months

Question 22

Withdrawal syndrome of antidepressants

Answer 22

FINISH

Flu-like symptoms (fatigue, muscle aches, headaches)
Insomnia
N/V
Imbalance (dizziness)
Sensory (paresthesia, electric shock sensations)
Hyperarousal (anxiety, agitation)

Question 23

Lifetime prevalence of MDD

Answer 23

5.8%

Question 24

Correlation with MDD

Answer 24

Physical illness & mental illness

Question 25

Risk factors for suicide in a general population (6)

Answer 25

1. Poor 2. Lonely 3. Elderly 4. Man 5. Physical & mental illnesses 6. Previous attempts

Question 26

3 independent predictors of suicide

Answer 26

1. Coexisting physical illness 2. Delusion 3. History of attempted suicide with using highly lethal means

Question 27

Theory for depression

Answer 27

Monoamine theory - decrease neurotransmitters in the brain - NE, 5-HT and dopamine

Question 28

Secondary causes of depression (3)

Answer 28

1. Medical conditions - CVD - endocrine disorders 2. Drug induced / iatrogenic 3. Psychological disorders

Question 29

General assessments prior to diagnosis and treatment (2)

Answer 29

``` 1. Psychiatric history eg maniac or hypomaniac episodes 2. Mental state exam (MSE) - assess for suicidal/homicidal ideations and risks - reassess on every interview ```

Question 30

SSRI examples (6)

Answer 30

1. Fluoxetine 2. Fluvoxamine 3. Escitalopram 4. Citalopram 5. Sertraline 6. Paroxetine

Question 31

SNRI examples (3)

Answer 31

1. Venlafaxine (worsens HTN) 2. Desvenlafaxine 3. Duloxetine

Question 32

Function of presynaptic autoreceptors

Answer 32

- negative feedback regulation - down-regulation of presynaptic autoreceptors lead to disinhibition of the release of neurotransmitters into synaptic space

Question 33

Antidepressants with long half life

Answer 33

1. Vortioxetine - 66h (2-3 days) 2. Fluoxetine - 4-6 days Less concern about withdrawal symptoms (FINISH)

Question 34

MAOi ADR

Answer 34

- hypertensive crisis

Question 35

Hypnotics

Answer 35

Benzodiazepines - diazepam - lorazepam - 2-4 weeks, short course, PRN

Question 36

Switching methods (2)

Answer 36

1. Cross-titration - recommended if daily use of serotonergic agents to non-serotonergic agents (cos need to taper dose gradually) to prevent serotonergic withdrawal syndrome - careful of serotonergic syndrome 2. Direct switch - complete washout required for MAOi

Question 37

Advice for patients taking alcohol and antidepressants

Answer 37

- space apart 4-6h | eg benzodiazepines & opioids = increased mortality

Question 38

Benzodiazepines discontinuation

Answer 38

- gradual discontinuation of long-term high dose use

Question 39

DDI (4)

Answer 39

1. Fluvoxamine - CYP1A2 inhibitor - CYP2C19 inhibitor 2. Fluoxetine & Paroxetine - CYP2D6 inhibitor 3. Bupropion - CYP2D6 inhibitor 4. Grapefruit juice - CYP3A4 inhibitor

Question 40

Augmentation of antidepressants

Answer 40

``` - add 2nd antidepressants with another MOA eg Mirtazapine (NDRI) ```

Question 41

Adjunctive SGAs (3)

Answer 41

1. Aripiprazole 2. Brexpiprazole 3. Quetiapine XR

Question 42

Treatment resistant depression

Answer 42

- no response to 2 adequate trials of antidepressants

Question 43

Treatment resistant depression management (2)

Answer 43

1. Electroconvulsant Therapy (ECT) - more invasive - refractory & more severe cases 2. Repetitive Transcranial Magnetic Stimulation (rTMS)

Question 44

Antidepressants with short half life (2)

Answer 44

1. Paroxetine | 2. Venlafaxine