Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective Serotonin Reuptake Inhibitors (SSRIs)

1. Definition & overview

• SSRIs are second-generation antidepressants that selectively and potently inhibit the neuronal serotonin transporter (SERT, also SLC6A4), with minimal effect on the norepinephrine transporter (NET), thereby prolonging serotonergic neurotransmission in the synapse (G&G 14e Ch.18, pp.343–4).
  • "Selective" denotes selectivity for SERT over NET — it does NOT mean selectivity for one 5-HT receptor subtype; SSRIs raise synaptic 5-HT non-selectively across all 5-HT₁–₇ receptors (G&G 14e Ch.18, pp.344–5).
• They are the first-line drugs for major depressive disorder (MDD) and for most anxiety disorders, owing to ease of use (starting dose ≈ therapeutic dose), tolerability, low overdose lethality, and generic low cost (Katzung 16e Ch.30, pp.572–3).
• The six classic SSRIs are fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram (Stahl Ch.7, pp.290–9; Padmaja 7e Ch.18, p.245).
  • Vilazodone (SERT inhibitor + 5-HT₁A partial agonist) and vortioxetine (multimodal) are SERT-active but are not classed as pure SSRIs — vilazodone is a SPARI and vortioxetine a multimodal serotonergic agent (Stahl Ch.7, pp.299–300; G&G 14e Ch.18, p.347).
• Relevant Indian undergraduate/PG competency: NMC PH 1.19 — mechanism, types, doses, side effects, indications and contraindications of antidepressant drugs (Padmaja 7e Ch.18, p.244).
• Fluoxetine (Prozac) was introduced in the USA in 1988 and rapidly became one of the most prescribed medications in clinical practice — it was developed in the search for high-affinity monoamine-reuptake agents lacking the histamine, muscarinic, and α-adrenergic affinity of the tricyclics (Katzung 16e Ch.30, p.562).