Selective Serotonin Reuptake Inhibitors (SSRIs)

Introduction

• SSRIs are second-generation antidepressants that selectively and potently inhibit the neuronal serotonin transporter (SERT / SLC6A4) with minimal effect on the norepinephrine transporter (NET), prolonging serotonergic neurotransmission. "Selective" denotes selectivity for SERT over NET — not for any one 5-HT receptor subtype (synaptic 5-HT rises non-selectively across all 5-HT₁–₇ receptors).
• They are the first-line drugs for major depressive disorder (MDD) and most anxiety disorders, owing to ease of use (starting dose ≈ therapeutic dose), tolerability, low overdose lethality and generic low cost — the safety advantage that displaced the TCAs and MAOIs.
• The six classic SSRIs are fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram and escitalopram. Fluoxetine (Prozac, 1988) was developed by seeking high-affinity reuptake blockade lacking the histaminic, muscarinic and α-adrenergic affinity of tricyclics. Vilazodone (a SPARI: SERT inhibitor + 5-HT₁A partial agonist) and vortioxetine (multimodal) are SERT-active but are not classed as pure SSRIs.