Sertraline: Mechanism of Action
Sertraline is a selective serotonin reuptake inhibitor (SSRI) used as a first-line treatment for depression, anxiety disorders, OCD, and PTSD.
Sertraline is a highly selective SERT inhibitor with minimal off-target activity, making it one of the best-tolerated and most versatile SSRIs.
How It Works
Sertraline inhibits SERT with high selectivity (serotonin:dopamine inhibition ratio ~1,600:1) and very low affinity for muscarinic, histaminergic, and alpha-adrenergic receptors — explaining its favourable tolerability compared to older antidepressants. Sertraline's sigma-1 receptor agonism may contribute to anxiolytic effects independent of SERT inhibition. Unlike fluoxetine, sertraline's shorter half-life allows faster dose adjustments. Its moderate CYP2D6 inhibition (less than paroxetine or fluoxetine) makes it less likely to cause drug interactions via this pathway.
Receptor / Target Profile
- •SERT (serotonin transporter) — Ki ~0.2 nM; primary target
- •Sigma-1 receptor — agonism; anxiolytic contribution
- •DAT (dopamine transporter) — weak inhibition (Ki ~25 nM); low clinical significance
- •CYP2D6 — moderate inhibitor; relevant for drug interactions
- •CYP2C19 — weak inhibitor
Pharmacokinetics
Onset of Action
Partial anxiety response within 1–2 weeks; full antidepressant effect 4–6 weeks; OCD response may take 8–12 weeks
Half-Life (t½)
~26 hours; active metabolite N-desmethylsertraline ~66 hours
Oral bioavailability ~44%. Hepatic metabolism via CYP3A4, CYP2D6, CYP2C19. Moderate CYP2D6 inhibitor. Renal elimination minimal. Unlike fluoxetine, short enough half-life to allow faster dose changes and cleaner washout for MAOI switching.
Conditions Treated with Sertraline
Questions about your medication?
Our AI Symptom Checker analyses your symptoms and suggests the most likely diagnoses — including relevant medications.
Use AI Symptom Checker →