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

Subclass of Drugs	Examples of Drugs
Tricyclic Antidepressants (TCA’s)	Tertiary Amines: Amitriptyline Imipramine Trimipramine Chlorimipramine Dothiepine Butriptyline Secondary Amines: Nortripyline Desimipramine Lofepramine
Monoamine Oxidase Inhibitors (MAOI’s)	Non-selective: Tranylcypromine MOA-A selective: Moclobemide Other: Isocarboxazid, Phenelzine, Selegiline
Serotonin-norepinephrine Reuptake Inhibitors (SNRI’s)	Venlafaxine Desvenlafaxine Duloxetine
5-HT2 Antagonists	Trazadone Nefazodone
Selective Noradrenaline Reuptake Inhibitors	Reboxetine
Tetracyclic and Unicyclic	Tetracyclic: Mianserin Mirtazepine Unicyclic: Bupropione
Circadian Rhythm Regulator	Valdoxane
Selective Serotonin Reuptake Inhibitors (SSRI’s)	Citalopram Fluoxetine Paroxetine Sertraline

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

All antidepressants inhibit the reuptake of neurotransmitters through selective receptors thus causing an increase in the concentration of the specific neurotransmitter.

3. How long does it take for the anti-depressive effects of these drugs to appear? What is the reason for this?

It takes 6-8 weeks to achieve optimal effects from the anti-depressant drugs. This is due to the fact that the drug has to build-up its blood level concentrations to a specific level to be able to work effectively.

4. How do the TADs and the selective serotonin reuptake inhibitors (SSRI’s) differ in respect to:

• Efficacy
• Side-effects
• Safety

	Tricyclic Antidepressants	Selective Serotonin Reuptake Inhibitors
Efficacy	These drugs have a higher affinity for reuptake transport receptors than for specific receptors. They are harder to tolerate due to their side effect profile and thus have a lower efficacy.	These drugs are more selective for serotonin transporters, they are much easier to tolerate due to a better side effect profile, thus they have a higher efficacy.
Side-effects	Sedation Anticholinergic: disturbed vision, dry mouth, etc. Orthostatic hypotension Precipitates mania Convulsions Weight gain, sexual disturbances Tremors, insomnia	Insomnia Tremors GIT disturbances Headaches Decreased libido Sexual dysfunction Acute anxiety Extrapyramidal side effects
Safety	When taken at the correct dosage, these drugs are considered safe. But they do have some potentially fatal side-effects and overdose of these drugs can be very dangerous.	Are generally safe for use, but in certain circumstances they may cause problems.

5. What is the action of mirtazapine?

The action of Mirtazepine is the blockade of inhibitory alpha-2 receptors which advances both Noradrenergic receptor activity and Serotonin release. It causes the blockade of Serotonin-3 and 2 receptors and cause the indirect stimulation of Serotonin-1 receptors.

6. What is the action of venlafaxine?

This drug is a SNRI drug which binds to the transporters of both serotonin and noradrenaline reuptake, it is more potent for serotonin receptors. The binding to these receptors presumably causes the enhancement of actions of both neurotransmitters.

7. What is the action of agomelatine?

This drug is an agonist for the Melatonin 1 and 2 receptors which help to regulate the circadian rhythms. It is also an antagonist for Serotonin 2C receptors which helps to improve sleep.

Brand, L.Prof.  2021.  Study Unit 10: Antidepressants. Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation]

Katzung, B.G., 2018. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education.