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

• Fluoxetine
• Sertraline
• Citalopram
• Paroxetine
• Fluvoxamine
• Escitalopram

• 2. SNRIs:
• Venlafaxine
• Desvenlafaxine
• Duloxetine
• Milnacipran

1. 3. TRICYCLIC ANTIDEPRESSANTS (TCAs):

Tertiary amine:

• Amitriptyline
• Imipramine
• Trimipramine
• Chlorimipramine
• Dothiepine
• Butriptyline

Secondary amine:

• Nortriptyline
• Desimipramine
• Lofepramine

• 4. TETRACYCLIC AND UNICYCLIC DRUGS:
• Bupropion
• Mirtazapine
• Amoxapine
• Maprotiline

• 5. 5-HT ANTAGONISTS:
• Trazodone
• Nefazodone
• Vortioxetine

• 6. MOAIs:
• Phenelzine
• Isocarboxazid
• Tranylcypromine
• Selegiline
• Moclobemide

• 7. NORADRENALINE RECEPTOR INHIBITORS (NARIs):
• Reboxetine
  8. CIRCADIAN RHYTHM REGULATOR:
• Agomelatine

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

Multipotent actions on numerous monoaminergic receptors due to non-specific increase in serotonin or noradrenaline.

• 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 for antidepressant agents to start being effective. This is due to the time it takes to have an effect on the serotonin receptors; either decreasing the number of 5-HT receptors or desensitizing the 5-HT receptors.

• How do the TADs and the selective serotonin reuptake inhibitors (SSRI’s) differ in respect of:
  1. efficacy
  2. side effects
  3. safety?

	TCAs:	SSRIs:
Efficacy:	Drugs need to be titrated to minimum effective dose.	Started at full dose.
Side effects:	Anticholinergic side effects, sedation, weight gain, sexual effects and discontinuation syndrome.	Nausea, GI-upset, diarrhea, decrease in sexual function and interest, headaches and insomnia/hypersomnia, weight gain and discontinuation syndrome.
Safety:	Not safe in overdose; the most commonly used drugs used in suicide. Causes lethal ventricular arrythmias and fibrillation as well as seizures.	Very safe with regards to overdose.

• What is the action of mirtazapine?

Blockade of alpha 2, 5HT2A, 5HT2C and 5HT3 receptors.

• What is the action of venlafaxine?

Serotonin and norepinephrine transporter antagonism. 

• What is the action of agomelatine?

Blockade of 5HT2C receptors with simultaneous stimulation of MT1/MT2 receptors (melatonergic receptors).

References:

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  Unpublished lecture notes on efundi, FKLG 312.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.  14^th ed.  California, San Francisco: McGraw-Hill Companies, Inc.