• MAO inhibitors: phenelzine, selegiline, tranylcypromine
• Tricyclic antidepressants: amitriptyline, clomipramine, imipramine
• Heterocyclic antidepressants: amoxapine, bupropion, mirtazapine
• 5-HT-NE reuptake inhibitors: duloxetine, venlafaxine
• 5-HT antagonists: nefazodone, trazodone
• Selective serotonin reuptake inhibitors: escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline

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

Through several mechanisms, most antidepressants cause potentiation of the neurotransmitter actions of NE, 5-HT, or both.

• How long does it take for the antidepressive effects of these drugs to appear? What is the reason for this?
  1. 1. Postmortem studies of patients do not reveal decreases in the brain levels of NE or 5-HT;
     2. Although antidepressant drugs may cause changes in brain amine activity within hours, clinical response requires weeks;
     3. Most antidepressants ultimately cause downregulation of amine receptors;
     4. Bupropion has minimal effects on brain NE or 5-HT;
     5. Brain-derived neurotrophic factor (BDNF) is depressed in the brains of depressed patients.

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

Most of the TCAs inhibit the reuptake of norepinephrine, though not dopamine, and as a result, they show some efficacy in remedying the disorder.

• • Side Effects

The adverse effects of TCAs, which result largely from their anticholinergic and antihistaminic properties, include the following: Sedation, confusion, dry mouth, orthostasis,  constipation, urinary retention, sexual dysfunction and weight gain.

• • safety?

Some tricyclic antidepressants are more likely to cause side effects that affect safety, such as Disorientation or confusion, particularly in older people when the dosage is too high. Increased or irregular heart rate.  More frequent seizures in people who have seizures.

• • What is the action of mirtazapine?

Mirtazapine is part of the tetracyclic antidepressants (TeCA) group that works by exerting antagonist effects on the central presynaptic alpha-2-adrenergic receptors, which causes an increased release of serotonin and norepinephrine.

• • What is the action of venlafaxine?

Venlafaxine works by increasing serotonin levels, norepinephrine, and dopamine in the brain by blocking transport proteins and stopping their reuptake at the presynaptic terminal.

• • What is the action of agomelatine?

Agomelatine has been shown to block 5-HT2C receptors within corticolimbic structures in the hippocampus. Hyperactivity of the 5-HT2C receptors may contribute to the symptoms of MDD and agomelatine induced 5-HT2C antagonism has been shown to increase the release of dopamine and norepinephrine in the frontal cortex.