SSRIs and SNRIs: mechanism, pharmacokinetics and adverse effects
How serotonin and noradrenaline reuptake inhibitors act and why their benefit is delayed, the half-life and CYP450 differences that drive washout times and interactions, and the mechanisms behind hyponatraemia, bleeding, QT prolongation, serotonin toxicity and discontinuation symptoms.
Tier 1Medical 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
- SSRIs block the serotonin transporter (SERT). SNRIs block SERT and the noradrenaline transporter (NET). Neither has much action at muscarinic, histamine or alpha-1 receptors, which is why they are safer in overdose than TCAs.
- The antidepressant effect is delayed 2 to 6 weeks although transporter blockade is immediate. Adverse effects such as nausea and agitation come first.
- They differ mainly in half-life and CYP inhibition. Fluoxetine is long-acting and inhibits CYP2D6; paroxetine is short-acting and inhibits CYP2D6; fluvoxamine inhibits CYP1A2; citalopram, escitalopram and sertraline have few interactions.
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Sources
- Therapeutic Guidelines: PsychotropicAU/NZTherapeutic Guidelines Limited, 2026
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- 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
- Citalopram and heart problems: changes to recommended doses (TGA safety alert)AU/NZTherapeutic Goods Administration, 4 November 2011
- Taylor DM, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines in Psychiatry (15th ed.)Wiley-Blackwell, 2025
- Last updated
- 14 November 2026
What changed
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