Monoamine
oxidase inhibitors
(MAOI)
Inhibit monoamine oxidase, the principal degradative
enzyme.
Non-selective
irreversible (nialamide)
Subtype-selective MAOIA and
MAOIB (clorgyline, deprenyl)
Reversible inhibitor of monoamine oxidase A (RIMA)
(moclobamide)
Side
effects: interaction with foodstuffs containing
tyramine causing increased release of NA and thus
increased blood pressure. Revesible inhibitors have
less side-effects but are less active.
(2)
Tricyclic
antidepressants
(TCA)
(imipramine, amitriptyline, clomipramine ...)
Inhibit the reuptake of serotonin and noradrenaline thus
increasing synaptic levels
Side
effects: interaction with cholinergic muscarinic,
alpha1 adrenergic and histaminergic
H1 receptors causing dry mouth, constipation,
blurred vision, orthostatic hypotension, and
sedation. Can be lethal in overdose.
Selective
serotonin reuptake inhibitors
(SSRI)
(fluoxetine, paroxetine, sertraline, citalopram...)
Inhibit selectively the reuptake of serotonin without
effects on postsynaptic receptors
Side
effects: stimulation of 5-HT3 receptors
causing nausea, gastrointestinal upset, diarrhoea and
headache; stimulation of 5-HT2 receptors
causing agitation, anxiety, panic attacks, insomnia and
sexual dysfunction;
Noradrenaline
reuptake inhibitors
(NARI)
(reboxetine)
Inhibit selectively the reuptake of noradrenaline
without effects on postsynaptic receptors
Side
effects: stimulation of alpha1 noradrenaline
receptors causing sweating and dyuria
Serotonin and
noradrenaline reuptake inhibitors
(SNRI)
(milnacipran, venlafaxine, duloxetine)
Inhibit the reuptake of both serotonin and
noradrenaline without effects on postsynaptic
receptors
Side
effects: those ofboth the SSRI and the NARI but to a
much lesser degree.
Alpha2 receptor
antagonists
(mianserin, mirtazapine)
Stimulate the release of noradrenaline by blocking
presynaptic inhibitory autoreceptors
Side
effects: sedation and weight gain
Potential
antidepressants undergoing
clinical trials
- Substance P
(NK1 neurokinin) receptor
antagonists
- CRF
(corticotrophin-releasing factor receptor
antagonists
- glucocorticoid
receptor antagonists
- vasopressin
receptor antagonists
- melatonin
receptor agonists
1.
Artigas F, Nutt DJ, Shelton R. Mechanism of action of
antidepressants. Psychopharmacol Bull 2002; 36 Suppl 2:
123-132.
2. Parker G, Roy K, Wilhelm K,
Mitchell P. Assessing the comparative effectiveness of
antidepressant therapies: a prospective clinical practice
study.J Clin Psychiatry. 2001;62:117-25.
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