9 Antidepressant Drugs

Question 1

Mechanism of antidepressants

Answer 1

1) Inhibit serotonin or noradrenaline reuptake
2) Block serotonin 5HT 2A receptor
3) Inhibit the activity of enzymes MAO

Question 2

Types of depression

Answer 2

1) Major depression: genetically predisposed
2) Reactive/ situational depression: induced by life events, generally resolved once the individual is able to adapt to the situation
3) Bipolar affective disorder
4) Postpartum depression
5) Seasonal affective disorder (SAD)

Question 3

Cause

Answer 3

• Unknown cause
• Change in the connectivity between limbic system and prefrontal cortex
• Monoamine theory: caused by functional deficit of monoamine neurotransmitters (noradrenaline and serotonin)

Question 4

Important transmissions

Answer 4

Reuptake transporters:
Serotonin transporter
NA transporter

Autoreceptors:
alpha 2 adrenoceptor
5HT1A/1B receptor

Question 5

Types of antidepressant

Answer 5

1) MAOI
2) Monoamine reuptake inhibitors:
TCA
SSRIs
SNRIs
NRIs
3)Atypical antidepressants

Question 6

MAOIs

Answer 6

Mechanism:
Inhibit MAO
(MAO A for metabolising NA, Adrenaline, Serotonin
MAO B for metablosing Dopamine)

Examples:

• Phenelzine
• Moclobemide

Side effects: agitation, insomnia, nausea

Question 7

Phenelzine

Answer 7

Irreversibly inhibit both MAO A and MAO B

Can cause cheese reaction as tyramine cannot be metabolised by MAO

Much less used now

Question 8

Moclobemide

Answer 8

Reversibly inhibit MAO A selectively

Does not cause cheese reaction

Enhance the action of anti-muscarninic drugs

Question 9

TCA

Answer 9

Mechanism: Inhibit 5HT and NA reuptake ( by competition for the binding site of amine transporter)

Examples: Amitriptyline, nortriptyline, imipramine, desipramine

Side effects: mainly due to the inhibition of alpha 1, muscarinic and histamine receptors ( i.e. postural hypertension, anti-muscarinic effects, sedation)

Question 10

Amitriptyline & Nortriptyline

Answer 10

Amitriptyline is the prodrug of Nortriptyline

Question 11

Imipramine & Desipramine

Answer 11

Imipramine is the prodrug of desipramine

Question 12

SSRIs

Answer 12

Mechanism:
Highly selectively inhibit 5HT reuptake

Similar efficacy with TCAs but fewer side effect and relatively safer than
TCAs when overdose

Examples: fluoxetine (Prozac), citalopram, paroxetine, sertraline

SIde effects: nausea, diarrhea, agitation, insomnia sexual dysfunction

Can cause serotonin syndrome with MAOIs / TCAs

Can cause BZD build up with benzodiazepine

Question 13

NRI

Answer 13

Mechanism: Inhibit NA and DA reuptake

Example: Bupropion

Side effects: headache, agitation, dry mouth, insomnia

Question 14

SNRI

Answer 14

Mechanism: Inhibit NA, 5-HT and DA reuptake

Example: venlafaxine

Side effects: headache, insomnia, sexual dysfunction, dry mouth, dizziness, sweating, decreased appetite, withdrawal effects

Question 15

Atypical antidepressants

Answer 15

Mechanism: monoamine receptor antagonist

Examples: mianserin, trazodone

Side effects:

Question 16

Mianserin

Answer 16

Alpha 2 receptor antagonist–> increases NA and 5HT

Side effects: seizure, type 1 hypersensitivity, agranulocytosis

Question 17

Trazodone

Answer 17

Block postsynaptic 5 HT2C receptor–> increase activity of DA and NA in the frontal cortex

Also weak 5-HT uptake inhibitor

Side effects: sedation, cardiac arrythmias

Question 18

Antidepressant time lapse

Answer 18

Acute effect: Increase 5HT at the soma and the dendrites of the raphe nucleus–> increase activation of auto-inhibitory 5 HT1A receptors–> inhibit firing of the 5HT releasing neurons

Chronic effect: Auto-inhibitory receptors desensitised–> decrease auto-inhibition increasing neuronal firing + upregulation of postsynaptic 5HT receptors