vilazodone

General Information

Vilazodone (Viibryd) is a serotonin reuptake inhibitor and 5-HT1A partial agonist approved for adult major depressive disorder; it offers an SSRI-like efficacy profile with a modest signal for less sexual dysfunction in some comparative studies.

Because food increases exposure twofold, every dose must be taken with a meal (≥350 calories)—a critical counseling point to avoid treatment failure in serious mental illness care plans.

The compare view and the vilazodone evidence feed can help contrast activation, GI tolerability, and meal requirements against other SSRIs before switching therapies or adding augmentation.

Consider for patients who experienced SSRI-related sexual dysfunction or weight gain, but reinforce food-dependent absorption and GI tolerability strategies during titration.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Combines high-affinity serotonin transporter inhibition with partial agonism at 5-HT1A receptors, potentially mitigating anxiety and sexual adverse effects.

Shows negligible affinity for adrenergic, dopaminergic, histaminic, or muscarinic receptors, contributing to a relatively neutral cardiometabolic profile.

• SERT inhibition.
• 5-HT1A partial agonism (~60% intrinsic activity).
• Minimal off-target receptor binding.

Metabolism and Pharmacokinetics

• Bioavailability increases roughly 50–70% with food; median Tmax 4–5 hours fed (≈6 hours fasting).
• Extensively metabolized by CYP3A4 (primary) with minor contributions from CYP2C19 and CYP2D6 to inactive metabolites; ~96% protein bound.
• Terminal half-life ≈25 hours; about 35% of a dose is recovered in urine and 33% in feces as metabolites (<1% unchanged). No dosage adjustment is required for mild-to-moderate renal or hepatic impairment, but severe hepatic impairment has not been studied.

Dosing and Administration

• Initiate 10 mg once daily with food for 7 days, increase to 20 mg once daily for 7 days, then advance to 40 mg once daily with food if tolerated.
• Limit to 20 mg/day when co-administered with strong CYP3A4 inhibitors (ketoconazole, clarithromycin); monitor carefully with moderate inhibitors. Avoid strong CYP3A4 inducers (carbamazepine, rifampin, St. John’s wort) because exposure is markedly reduced.
• If therapy is interrupted for >3 days, restart the titration to minimize GI adverse effects; taper to 20 mg then 10 mg over at least 1 week when discontinuing to limit withdrawal symptoms.

Adverse Effects

Interactions

• Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) increase exposure—limit to 20 mg/day; monitor when moderate inhibitors are used.
• Strong CYP3A4 inducers (carbamazepine, rifampin, phenytoin, St. John’s wort) significantly lower concentrations; avoid combination or select an alternative antidepressant.
• Contraindicated with MAOIs, linezolid, and methylene blue—observe 14-day washouts to reduce serotonin syndrome risk.
• Additive serotonergic effects with SSRIs, SNRIs, triptans, lithium, or tramadol; counsel on serotonin syndrome symptoms and monitor closely.
• Heightened bleeding risk when combined with NSAIDs, antiplatelets, or anticoagulants—ensure gastroprotection when appropriate.

Other Useful Information

• Counsel patients to take vilazodone with a substantial meal at the same time each day; missed doses taken without food may deliver subtherapeutic exposure.
• Monitor for early insomnia, restlessness, and GI upset; supportive care (taking with breakfast, hydration, antidiarrheals) can improve adherence.
• Discuss pregnancy planning; data are limited, so weigh maternal benefit versus fetal risk and coordinate with obstetrics for individualized decisions.

References

1. Vilazodone hydrochloride tablets prescribing information — DailyMed (2023)
2. Vilazodone for major depressive disorder: systematic review of efficacy and safety — International Journal of Clinical Practice (2012)
3. Vilazodone, levomilnacipran and vortioxetine for major depressive disorder — International Journal of Clinical Practice (2015)
4. Vilazodone IN Major Depressive Disorder: Randomized, Active AND Placebo Controlled Trial — Cureus (2021)
5. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
6. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)