Classification of Vilazodone
Vilazodone is classified as a selective serotonin reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist, also termed a serotonin partial agonist-reuptake inhibitor (SPARI). 1
Official FDA Classification
The FDA drug label explicitly states that vilazodone hydrochloride is "a selective serotonin reuptake inhibitor and a 5HT1A receptor partial agonist" for oral administration. 1
Dual Mechanism of Action
Vilazodone possesses two distinct pharmacological properties that define its classification:
SSRI component: Vilazodone binds with high affinity to the serotonin reuptake site (Ki = 0.1 nM) and potently inhibits serotonin reuptake (IC50 = 1.6 nM), with minimal activity at norepinephrine (Ki = 56 nM) or dopamine (Ki = 37 nM) reuptake sites. 1
5-HT1A partial agonist component: Vilazodone binds selectively with high affinity to 5-HT1A receptors (IC50 = 2.1 nM) and functions as a partial agonist at these receptors, though the net result of this action on serotonergic transmission and its role in antidepressant effect remain unknown. 1
Alternative Classification Terminology
The term "serotonin partial agonist-reuptake inhibitor (SPARI)" has been used in the medical literature to describe vilazodone's unique dual mechanism, distinguishing it from traditional SSRIs that lack 5-HT1A receptor partial agonist activity. 2, 3, 4
Distinction from Other Antidepressant Classes
Vilazodone does not fit into traditional antidepressant categories and is sometimes classified as "other antidepressant" alongside medications like bupropion, mirtazapine, trazodone, and vortioxetine that have unique mechanisms distinct from standard SSRIs, SNRIs, or tricyclic antidepressants. 5
Clinical Implications of Classification
The dual mechanism was designed based on the hypothesis that 5-HT1A receptor partial agonism combined with SSRI activity might produce faster onset of action, greater efficacy, and better tolerability (particularly reduced sexual side effects) compared to traditional SSRIs, though direct clinical proof of these advantages remains limited. 2, 3, 4