Using your textbooks, draw up a classification of the drugs that are used as antidepressants.

SSRI’s	SNRI’s	TCA’s	5-HT antagonist	Tetracyclic and Unicyclic	MOAI	NARI
Fluoxetine Sertraline Citalopram Paroxetine Escitalopram	Venlafaxine Duloxetine Desvenlafaxine	Tertiary amine: Impramine Amitriptyline Trimipramine Chlorimipramine Secondary amine Nortriptyline Desimipramine	Trazodone Nefazodone Vortioxetine	Bupropion Mirtazapine Amoxapine Maprotiline	Phenelzine Isocarboxazid Tranylcypromine Selegiline Moclobemide	Reboxetine

• What do the existing drugs all have in common regarding their mechanisms of action?

All of these drugs promote monoamine activity by increasing NA and serotonin levels at the central synapse, by either re-uptake inhibition, degradation inhibition or the blockage of the presynaptic alpha 2 receptor.

• How long does it take for the antidepressive effects of these drugs to appear? What is the reason for this?

The onset is very slow and can take up to 6-8 weeks for effects to be seen due to the action that of the anti-depressants that still needs to be altered in the brain.

• How do the TADs and the selective serotonin reuptake inhibitors (SSRI’s) differ in respect of:

Efficacy  

TAD: needs to be titrated to the minimum effective dose whereas SSRI’s can be started on the full dose. All these drugs does however take 6-8 weeks for effects to be seen.

Side effects

 TAD: sedation, tremors, insomnia, disturbed vision, dry mouth, urinary retention, confusion, orthostatic hypotension, dysrhythmias convulsions, weight gain and sexual dysfunction. 

SSRI: Insomnia, tremors, GIT disturbances, headache, ↓ libido, sexual dysfunction, anxiety (acute), EPS, withdrawal syndrome. ↓ appetite, non-sedating,  acute increases 5-HT synaptic activity = acute anxiety, later 5-HT reduces again.

Safety

TAD: Not safe in overdose but it is commonly the drug used for suicide. It causes lethal ventricular arrythmias and fibrillation and seizures.

SSRI: it is very safe with regards to overdose and this drug is better tolerable.  

• What is the action of mirtazapine?

It blocks the action of alpha 2, 5-HT2A, 5-HT2c and 5-HT3 receptors. It also blocks histamine 1 and alpha 1 and causes the indirect stimulation of 5-HT1A

• What is the action of venlafaxine?

Blocks both 5-HT - and NA re-uptake, more potent for 5- HT than for NA. Moderately selective blockade of SERT and NET..

• What is the action of agomelatine?

Antagonist: 5-HT2C

Agonist: Melatonergic R’s – MT1 & MT2.  and NA release.