Tricyclic, MAOI and atypical antidepressants
The receptor profile of tricyclics and how it predicts their adverse effects and lethal toxicity, irreversible and reversible MAO inhibition and the tyramine reaction, and the mechanisms of mirtazapine, agomelatine, vortioxetine, reboxetine, bupropion and esketamine.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Tricyclics (TCAs) inhibit serotonin and noradrenaline reuptake but also block muscarinic, histamine and alpha-1 receptors and cardiac sodium channels. That "dirty" profile explains their adverse effects and their lethality in overdose.
- MAOIs stop breakdown of monoamines. Irreversible non-selective MAOIs (phenelzine, tranylcypromine) carry the tyramine reaction and dangerous interactions. Moclobemide is a reversible MAO-A inhibitor with far fewer problems.
- Atypical antidepressants each have a distinct mechanism: mirtazapine (alpha-2 antagonist), agomelatine (melatonergic), vortioxetine (multimodal serotonergic), reboxetine (NRI), bupropion (noradrenaline and dopamine reuptake inhibitor) and esketamine (NMDA antagonist).
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Sources
- Therapeutic Guidelines: PsychotropicAU/NZTherapeutic Guidelines Limited, 2026
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- Taylor DM, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines in Psychiatry (15th ed.)Wiley-Blackwell, 2025
- Malhi GS et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2021;55:7-117AU/NZRANZCP, 2021
- Hicks JK et al. CPIC guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther 2017;102:37-44Clinical Pharmacogenetics Implementation Consortium, 2017
- Last updated
- 14 November 2026
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