Viibryd (Vilazodone) Drug Classification
Viibryd (vilazodone) is a selective serotonin reuptake inhibitor (SSRI) with additional 5-HT1A receptor partial agonist activity, making it a dual-mechanism antidepressant within the SSRI class. 1
Primary Classification
Vilazodone is officially classified as an SSRI by the FDA, as it selectively inhibits serotonin reuptake with high affinity (Ki = 0.1 nM) and potency (IC50 = 1.6 nM), while having minimal affinity for norepinephrine (Ki = 56 nM) or dopamine (Ki = 37 nM) reuptake sites 1
The drug has a unique dual mechanism that distinguishes it from traditional SSRIs: it combines selective serotonin reuptake inhibition with partial agonist activity at 5-HT1A receptors (IC50 = 2.1 nM) 1
Mechanism of Action
Vilazodone enhances serotonergic activity in the CNS through selective inhibition of serotonin reuptake, similar to other SSRIs like fluoxetine, sertraline, paroxetine, escitalopram, citalopram, and fluvoxamine 2, 1
The 5-HT1A partial agonist component represents a novel addition to SSRI pharmacology, though the net result of this action on serotonergic transmission and its contribution to antidepressant efficacy remains incompletely understood 1
The mechanism parallels other SSRIs in that it blocks presynaptic serotonin reuptake, increasing serotonin availability at the synaptic cleft, which over time leads to downregulation of inhibitory serotonin autoreceptors and increased serotonergic neuronal firing 2
Clinical Context Within SSRI Class
Vilazodone is grouped with other SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) in clinical guidelines, as the primary mechanism of action is sufficiently similar to warrant extension of SSRI class findings to vilazodone 2
The American Academy of Child and Adolescent Psychiatry includes vilazodone in the list of SSRIs currently marketed in the United States for anxiety and mood disorders 2
Like other SSRIs, vilazodone carries similar warnings and precautions, including risks of serotonin syndrome when combined with other serotonergic agents (MAOIs, other antidepressants, tramadol, dextromethorphan), hypertensive crisis risk with sympathomimetic drugs, and monitoring requirements for suicidality 2
Important Distinguishing Features
Vilazodone requires administration with food to optimize bioavailability (72% with food versus 50% reduction in AUC and 60% reduction in Cmax when fasted), which differs from most other SSRIs 1
The terminal half-life is approximately 25 hours, placing it in the intermediate range among SSRIs (shorter than fluoxetine's very long half-life, longer than paroxetine's shorter half-life) 1
Metabolism occurs primarily via CYP3A4 with minor contributions from CYP2C19 and CYP2D6, requiring consideration of drug interactions with CYP3A4 inhibitors and inducers 1