Depression

Question 1

What are the symptoms of Major Depressive Disorder?

Answer 1

In SAD CAGES:
- Interest loss
- Sleeping more or less
- Appetite loss
- Depressed mood
- Concentration difficulties
- Activity level reduced
- Guilt
- Energy decline
- Suicidality

At least 5 out of 9 symptoms over a 2-week period

PHQ-9 Score Moderate-severe > 10 require treatment with pharmacologicals

Question 2

How do you conduct a suicide inquiry?

Answer 2

1. Ideation (Frequency, intensity, duration)
2. Plan (Timing, Location, Lethality)
3. Ambivalence (Reasons to live vs die)
4. Intent (Extent to which the plan is expected to be carried out)

Question 3

What is the pathophysiology of MDD?

Answer 3

Biological basis
1. Hormone: Cortisol
2. Monoamine hypothesis: NE, 5HT, DA deficit

Genetic basis: S/S genotype most vulnerable to depression compared to L/L genotype

Medical Disorders
1. Endocrine (Thyroid, DM, Cushing)
2. Cardiovascular (CAD, CHF, MI)
3. Others: Deficiency states, infections, metabolic disorders, neurologic, malignancy

Question 4

Differential Diagnosis

Answer 4

Adjustment Disorder: 3 months of onset of stressor but symptoms don’t persist for 6 months once stressor is terminated

Acute Stress Disorder: 1 month of a traumatic event lasting 3 days to 1 month

Mania: To make sure not to start antidepressants

Delirium: Acute onset impairing consciousness and memory

Dementia: Stepwise onset and consciousness remains but short/long-term memory is poor

Question 5

First Line Antidepressants

Answer 5

Mirtazapine
SSRIs
SNRIs
Bupropion

Question 6

What are the phases of treatment?

Answer 6

1. Acute Phase Treatment
   - Adequate trial of 4-8 weeks
   - Response to treatment:
   — Physical Sx in 1-2 weeks
   — Mood Sx in 4-8 weeks
2. Continuation Phase Treatment
   - 6 to 12 months at least in total

Question 7

Why is there delayed onset of effectiveness of antidepressants?

Answer 7

Downregulation of presynaptic autoreceptors in the synapse is a GRADUAL process

Question 8

Compare the reuptake antagonism amongst antidepressants

Answer 8

SSRIs: Serotonin reuptake
SNRIs: Serotonin and NE reuptake
Bupropion: NE reuptake
Mirtazapine: Not by reuptake mechanism but by autoreceptor blockade
TCAs: Highly antagonising NE and 5HT

Question 9

Compare the side effect profile amongst antidepressants on anticholinergic, sedative, orthostatic and seizure effects

Answer 9

SSRIs: Seizures in rare cases (Except escitalopram)
SNRIs: Some of each
Bupropion: Seizures!!
Mirtazapine: Sedative, orthostatic, some anticholinergic

Question 10

Compare the PK characteristics of antidepressants (Half-life, bioavailability, metabolism)

Answer 10

Fluoxetine and Vortioxetine have long half-lives (4-6 days and 66 hours)

Sertraline has poor bioavailability but it increases when taken with food which increases absorption

All are quite highly protein bound

Clinically important active metabolites formed:
1. Fluoxetine => Norfluoxetine
2. Venlafaxine => O-desmethylvenlafaxine
3. Bupropion => 3 active metabolites
4. All TCAs form metabolites

Question 11

Compare the characteristics amongst the SSRIs

Answer 11

Fluoxetine has long half-life = No need gradual tapering for antidepressant discontinuation

Paroxetine is most anticholinergic and sedating with short half-life

Escitalopram has QTc prolongation at high doses in elderly

Question 12

Which SNRI is special?

Answer 12

Duloxetine: Diabetic peripheral neuropathy, chronic musculoskeletal pain

Question 13

Why is mirtazapine more beneficial than SSRIs?

Answer 13

Reverse GI and sexual SE

Increase appetite and weight gain

Question 14

What are pros and cons of using bupropion over SSRIs?

Answer 14

Reduced sexual SE

Caution in seizures, psychosis and eating disorders

Question 15

What is the most important side effect of MAOi? Which MAOi has the better safety profile?

Answer 15

Hypertensive crisis

Moclobemide (RIMA)

Question 16

What adjunct medications can be used in MDD?

Answer 16

SGAs (Aripiprazole, Brexpiprazole, Quetiapine)
- Olanzapine + Fluoxetine for TRD

Esketamine (NMDA receptor antagonist)
- Add on to SSRI/SNRI for TRD

Hypnotic PRN (See Insomnia drugs)

Question 17

Dosing for Amitriptyline, Clomipramine, Fluoxetine, Mirtazapine, Desvenlafaxine ER

Answer 17

Amitriptyline 50-100 mg/day (Max 300 mg)
Clomipramine 25 mg/day (Max 300 mg)
Fluoxetine 20 mg OM (Max 80 mg)
Mirtazapine 15 mg/day (Max 45 mg)
Desvenlafaxine 50 mg/day (Max 100 mg)

Question 18

When do we switch antidepressants for MDD patients?

Answer 18

Ineffective or intolerable in 2 to 4 weeks

Question 19

How should drug switching be done for MDD?

Answer 19

1. Cross-titration: Monitor serotonin syndrome for serotonergic agent combinations
2. Direct switching: Stop one serotonergic drug, start another serotonergic drug
3. Indirect switching: Gradual tapering of serotonergic agent every 2 weeks, start non-serotonergic agent (Bupropion)
4. MAOi switching: Washout period (24h for moclobemide to another antidepressant; 1 week for another antidepressant to moclobemide)

Question 20

What drugs can be used to augment existing antidepressants?

Answer 20

1. Mirtazapine, Bupropion
2. Adjuncts: Quetiapine, Aripiprazole, Brexpiprazole

Question 21

What is TRD and how to treat?

Answer 21

No response to ≥ 2 adequate trials

Options:
1. ECT neurostimulation
2. Symbyax PO capsule (Olanzapine, fluoxetine)
3. Spravato Nasal spray (Esketamine)

Question 22

What should you take note in elderly? What agents can be used instead

Answer 22

Hyponatremia (SSRIs)

Mirtazapine, Bupropion, Agomelatine

Question 23

Describe the presentation of serotonin syndrome

Answer 23

Mild: Insomnia, anxiety, N/D, HTN, HR rise

Moderate: Agitation, tremor, mydriasis, flushing, diaphoresis, fever, myoclonus

Severe: Hyperthermia, confusion, respiratory failure, coma, death