Classification of the anti-depressants;  

• Tricyclic antidepressants (TAD)

Secondary Amines	Tertiary Amines
NA selective	5-HT selective (alphalytic and many anti-cholinergic SE thus CI in elderly with prostate hypertrophy)
Nortriptyline	Amitriptyline (Rx for chronic pain)
Desimipramine	Imipramine (Rx for enuresis, acute panic, phobias)
Lofepramine	Trimipramine
Amoxapine	Chlorimipramine (Rx for OCD)
Maprotyline (dose related convulsions)	Dothiepine
	Butriptyline

• Monoamine oxidase inhibitors (MAOI)
  • Tranylcypromine (non-selective, reversible blocking, long blackade)
  • Maclobemide (A selective, reversible blocking)
  • Selegiline & Rasagiline (B selective)
• Selective serotonin re-uptake inhibitors (SSRI)
  • Fluoxetine (Effects glucose levels, Rx for OCD, can immediately be given at a high dose)
  • Paroxetine (Short t_1/2, few CV SE, severe withdrawal reaction is seen, Rx for PTSD)
  • Fluvoxamine (Rx for OCD)
  • Sertraline (Rx for OCD)
  • Citalopram 
  • Escitalopram  
• Serotonin, noradrenaline reuptake inhibitors (SNRI)
  • Duloxetine
  • Venlafaxine (Causes hypertension as a SE while all the others cause hypotension)
• Selective noradrenaline reuptake inhibitors (NARI)
  • Roboxetine (Not cardio toxic, no affinity for any NT receptors)
• Tetracyclic & Unicyclic anti-depressants 
  • Mianserin (Not used due to blood deviations)
  • Mirtazepine (No sexual dysfunction)
  • Bupropione (No sexual dysfunction, lower doses used as Rx for nicotine withdrawal, decreases convulsion threshold)
• Serotonin receptor modulators 
  • Trazodone (Off-label hypnotic)
  • Vortioxetine (MANY MoA’s)
  • Nafazodone (Hepatotoxicity)
• Circadian rhythm regulators 
  • Agomelatine 

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

Anti-depressants increase NA and 5-HT at central synapses. This is done by;

Re-uptake inhibition, Degradation inhibition and by blocking presynaptic a2 autoreceptors. 

How long does it take for the anti-depressive effects of these drugs to appear? 

14-21 days since it takes two weeks or longer for the synthesis of neurotropic factors which are needed for neural plasticity, resilience and neurogenesis. 

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

• • Efficacy

Almost all the anti-depressants have the same efficacy and the drug choice depends on patient response. One factors is that TAD are titrated upwards until the MEC is reached which SSRI can immediately be given as full dosages. 

• • Side Effects

TAD = Weights gain, convulsions, sedation, tremors, insomnia, anticholinergic effects, orthostatic hypotension, dysrhythmias, tachycardia, psychosis, precipitation of mania, sexual dysfunction.

SSRI = GI side effects, headaches, EPS like twitches and muscle cramps, insomnia, tremors, decreased libido, sexual dysfunction, anxiety, withdrawal symptoms, CNS stimulating effects like agitation, anxiety and jitters. 

• • Safety

SSRIs are the preferred Ads along with newer drugs because they have a better side-effect profile, safer in acute overdose and SSRI’s can suppress appetite, overweight patients may lose weight.

TAD have cardiovascular side effects (orthostatic hypotension, dysrhythmias, tachycardia) which make them riskier in people with already existing cardiovascular conditions. 

What is the action of mirtazepine?

Mirtazapine is a NA and specific 5-HT anti-depressant. It also blocks H₁(sedation, weight gain) and a₁(postural hypotension) receptors. There is further blockade of the a₂ receptors which then advances NA (auto) and 5-HT (hetero) release. There is indirect stimulation of 5-HT_1Awhich gives mirtazepine anxiolytic properties. Lastly there is blockade of 5-HT₃ (anxiolytic and antiemetic) and 5-HT₂ receptors. 

What is the action of venlafaxine?

Venlafaxine is a serotonin and noradrenaline reuptake inhibitor. But 5-HT is blocked more potently. 

What is the action of agomelatine?

Agomelatine is a MT₁and an MT₂ agonist (this is why it promotes and benefits sleep). It is also a 5-HT_2Cantagonist (this is why it benefits the anti-depression action and also leads to disinhibition of DA and NA release).