Antidepressants (PSYCH DRUGS)

Question 1

First-line antidepressant

Answer 1

SSRI - selective serotonin receptor inhibitor (few SE because selective action on serotonin alone)

Question 2

SSRI
1. Full name
2. MOA

Answer 2

Selective Serotonin Reuptake Inhibitor

• MOA: block serotonin reuptake by transmitting neurons -> elevated serotonin levels in synaptic space -> prolonged action on receiving neuron

Question 3

SSRI side effects - common AND uncommon

Answer 3

Common
1. Anxiety
2. Insomnia
3. Headache
4. Nausea
5. Diarrhea
6. Sexual dysfunction

Uncommon
1. Antidepressant-induced hypoNa (common in old people, manifestations: lethargy, muscle ache, nausea, more severe- cardiac failure, confusion, seizure)
2. GI bleed/GI ulcer
3. Serotonin syndrome (applies to antidepressants as a class)

Question 4

SSRI indications

Answer 4

1. Depression with anxiety/obsessional symptoms
2. Depression in elderly (due to benign SE profile)
3. Suicidal pt (safe in OD)
4. (conditions with serotonin deficiency) Panic disorder, social anxiety disorder, PTSD, OCD, bulimia nervosa

Question 5

SSRI examples AND dose

Answer 5

x5
1. Fluoxetine (20 mg OM)
2. Fluvoxamine (50 mg OM to 50 mg BD)
3. Paroxetine (20mg OM)
4. Sertraline (50mg OM)
5. Escitalopram (10mg OM)

Question 6

SNRI Full name + MOA

Answer 6

Serotonin noradrenaline reuptake inhibitor

MOA: dual action - block serotonin and noradrenaline reuptake transporters

Question 7

SNRI side effects

Answer 7

Similar to SSRI PLUS adrenergic SE

1. Anxiety
2. Nausea
3. # Sexual dysfunction
4. Tachycardia, HTN, mydriasis, diaphoresis
5. Dry mouth
6. Constipation

Question 8

SNRI example and dose

Answer 8

1. Venlafaxine (75mg/day)
2. Desvenlafaxine (50mg/day)
3. Duloxetine (60mg/day)

Question 9

SNRI indications

Answer 9

1. Depression
2. Generalised anxiety disorder
3. Pain symptoms in depression

Question 10

Duloxetine added benefits

Answer 10

Effect on pain symptoms in depression eg. Back ache

Question 11

Which SNRI has Discontinuation symptom?

Answer 11

Venlafaxine

Question 12

TCA MOA

Answer 12

MOA: dual action - block both serotonin and noradrenaline transporters PLUS block cholinergic, histamine, alpha-adrenergic receptor, sodium channel ***dirty drug!! broad spectrum

Question 13

TCA side effect

Answer 13

1. Dry mouth, tachycardia, memory impairment (bad for elderly), acute closed angle glaucoma [muscarinic M1 receptor blockade]
2. Sedation, weight gain [block histamine receptor]
3. Postural hypotension [block alpha adrenergic receptor]
4. Arrythmia ***overdose + wide QRS complex = TCA OD seizure [block Na channel]

Question 14

TCA efficacy, safety

Answer 14

Efficacy: superior to other antidepressants
Safety: highly lethal in OD (VF, seizure 2’ to Na channel blockade)

Question 15

TCA indication

Answer 15

1. Severe depression (superior to newer agents)
2. Specific dx (chronic pain, fibromyalgia, migraine, insomnia) - use amitriptyline
3. Specific dx (OCD) - use clomipramine

Question 16

Avoid TCA in

Answer 16

1. Elderly
2. Physically ill
3. The suicidal (if really need to prescribe, do safety advice - family keep drugs for pt)

Question 17

TCA examples and dose

Answer 17

x4
1. Amitriptyline (25-150mg)
2. Imipramine (25-150mg)
3. Dothiepin (25-150mg)
4. Clomipramine (25-100mg)

Question 18

Noradrenaline Dopamine Reuptake Inhibitor MOA

Answer 18

MOA: block both dopamine and noradrenaline reuptake transporters

Question 19

Noradrenaline dopamine reuptake inhibitor example AND dose

Answer 19

Bupropion 150mg/day

Question 20

Noradrenaline dopamine reuptake inhibitor/Bupropion Side effects

Answer 20

1. Insomnia, agitation, anxiety (as a result of overstimulation ***rmb that bupropion can be used in ADHD!)
2. Seizures (due to effects of elevated dopamine levels on seizure threshold)

Has NO effect on sexual dysfunction

Question 21

Noradrenaline dopamine reuptake inhibitor Indications

Answer 21

1. Depression with anhedonia
2. Depression with fatigue
3. Smoking cessation
4. ADHD (child psych)

Question 22

Avoid noradrenaline dopamine reuptake inhibitor (bupriopion) in

Answer 22

1. Anxiety disorders
2. Panic attacks
3. Seizures

Question 23

NaSSA full name + MOA

Answer 23

Noradrenergic and Specific serotonergic antidepressant **diff from SNRI (block reuptake transporter) VS NaSSA (block receptors)

MOA: x3
1. Block presynaptic alpha 2 receptors of noradrenergic AND serotonergic pathways (which are normally responsible for -ve feedback) -> increases noradrenergic and serotonergic neurotransmission
2. Block postsynaptic serotonin 5HT2 AND 5HT3 receptors
3. block histamine 1 receptor -> sedating effect

Question 24

Side effects of NaSSA (Mirtazapine)

Answer 24

1. Sedation, weight gain (antihistaminergic effects)

***NO insomnia, nausea, sexual dysfunction (due to selective activity; increased serotonin binds to desired 5HT receptor ie. 5HT1A to exert therapeutic effect

Question 25

NaSSA indications

Answer 25

1. Antidepressant, anxiolytic effect 2. Depression with anxiety, insomnia, weight loss 3. Commonly used in elderly 4. No CYP450 inhibition -> less likely for drug drug interaction

Question 26

NaSSA example AND dose

Answer 26

Mirtazapine (30mg/day)

Question 27

Agomelatine MOA

Answer 27

Melatonin receptor agonist (active melatonin 1&2 receptors in suprachiasmatic nucleus of hypothalamus -> restore circadian rhythms -> resynchronise disturbed sleep/wake cycle in depressed pt

Question 28

Agomelatine side effects

Answer 28

1. Common: dizziness 2. Rare: hepatitis No daytime sedation, sexual dysfunction, weight gain Safe in overdose

Question 29

Indications for agomelatine

Answer 29

1. Depression with sleep disturbance 2. Depression with fatigue

Question 30

Agomelatine dose

Answer 30

25-50mg/day

Question 31

MOAI full name + MOA

Answer 31

Monoamine oxidase inhibitors (MAOI) MOA: **ir**reversibly inhibit monoamine oxidase -> both serotonergic AND noradrenergic pathways involved **THIRD LINE (extensive SE profile)

Question 32

MAOI side effect

Answer 32

1. Hypertensive crisis 2. Serotonin syndrome (interaction with serotonergic drugs)

Question 33

MAOI examples

Answer 33

X4 1. Selegiline 2. Isocarboxazid 3. phenelzine 4. Tranylcypromine

Question 34

RIMA full name + MOA

Answer 34

Reversible inhibitor of monoamine oxidase A (RIMA) - MOA: reversibly and selectively inhibit the enzyme MOA

Question 35

RIMA side effect

Answer 35

1. Insomnia Reduced risk of hypertensive crisis compared to MAOI

Question 36

Multimodal drugs examples AND dose

Answer 36

1. Vortioxetine (10mg/day) 2. SARI (serotonin antagonist/reuptake inhibitor)

Question 37

Vortioxetine MOA

Answer 37

- multimodal drug MOA: x2 1. Block serotonin receptor 2. Multiple actions on serotonin receptor -> downstream effect of adrenaline and acetylcholine in specific area of brain (pro-cognitive effect too)

Question 38

Vortioxetine side effect

Answer 38

Generally q tolerable 1. Nausea 2. Low sexual dysfunction No insomnia or weight gain

Question 39

Vortioxetine indication

Answer 39

Depression with cognitive dysfunction (rumination, indecision, inattention, poor conc)

Question 40

SARI full name + MOA

Answer 40

Serotonin antagonist/reuptake inhibitor MOA: x4 it is a serotonin modulator 1. Blocks post synaptic serotonin 5HT2A receptors **robustly** 2. Blocks presynaptic serotonin reuptake transporter **weakly** 3. Blocks histamine 1 receptor (-> sedating effect) 4. Blocks alpha adrenergic receptors (-> orthostatic hypotension, priapism)

Question 41

SARI side effects

Answer 41

1. Sedation 2. Orthostatic hypotension and priapism 3. Cardiac arrhythmias

Question 42

SARI indications

Answer 42

1. Hypnotic for insomnia in depression (lower dose as hypnotic: 25-150mg) 2. Antidepressant dose higher 150-600ng (but hard to tolerate cause too sedated)

Question 43

Serotonin syndrome symptoms

Answer 43

1. Tremor 2. Agitation (mental state) 3. Hyperreflexia, clonus (Neuromuscular hyperactivity) 4. HTN, tachycardia, diaphoresis, mydriasis (Autonomic hyperactivity)

Question 44

Dangerous complication of combination SSRI use?

Answer 44

Serotonin syndrome

Question 45

Strong inhibitors of CYP450 2D6

Answer 45

Bupropion, fluoxetine, paroxetine

Question 46

Concern with propranolol (beta blocker) and fluoxetine (SSRI)?

Answer 46

Fluoxetine: strong CYP2D6 inhibitor Beta blocker: major substrate of CYP2D6 Thus beta blocker in body system will increase due to inhibition of metabolism of propranolol

Question 47

Concerns with fluoxetine and phenytoin

Answer 47

Fluoxetine: moderate inhibitor CYP2C19 Phenytoin: major substrate of CYP2C19 Although fluoxetine moderate inhibitor, phenytoin has narrow therapeutic index

Question 48

Antidepressant discontinuation symptoms onset and symptoms

Answer 48

Onset: 3-5 days of stopping half-life antidepressant Symptoms: x4 1. Dizziness 2. Headache 3. Insomnia 4. Irritability

Question 49

Antidepressants prone to discontinuation symptoms

Answer 49

1. Fluvoxamine 2. Paroxetine

Question 50

Why the need to recognise discontinuation symptoms?

Answer 50

May mistaken for new physical illness

Question 51

What is the Black box warning?

Answer 51

Antidepressant for first few weeks: Increased risk of suicidality (for children and adults up to 24 years of age)

Question 52

Antidepressants that cause MINIMAL sexual dysfunction

Answer 52

1. Mirtazapine 2. Bupropion

Question 53

SARI examples of drug

Answer 53

1. Trazodone 2. Nefazodone

Question 54

Key symptom: anxiety Preferred antidepressant?

Answer 54

SSRI or SNRI Eg. Setraline (SSRI)

Question 55

Key symptom: cognitive difficulties (learning, memory, decision-making) Preferred antidepressant?

Answer 55

1. Duloxetine 2. Vortioxetine

Question 56

Key symptom: sleep disturbances eg insomnia Preferred antidepressant?

Answer 56

1. Mirtazapine 2. Agomelatine

Question 57

Key symptom: fatigue Preferred antidepressant?

Answer 57

Bupropion

Question 58

Key symptom: pain Preferred antidepressant?

Answer 58

Duloxetine, TCA

Question 59

Key symptom: melancholia (psychomotor retardation, diurnal mood variation) Preferred antidepressant?

Answer 59

TCA