VILAZODONE HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Vilazodone is a selective serotonin reuptake inhibitor (SSRI) and a partial agonist of the 5-HT1A receptor. It increases serotonin levels in the synaptic cleft by inhibiting its reuptake, and the 5-HT1A partial agonism may enhance serotonergic neurotransmission.
| Metabolism | Primarily metabolized via CYP3A4, with minor contributions from CYP2C19 and CYP2D6. Also undergoes non-CYP pathways including monoamine oxidase and conjugation. Inhibitors and inducers of CYP3A4 significantly alter vilazodone exposure. |
| Excretion | Primarily hepatic metabolism via CYP3A4, with approximately 1% excreted unchanged in urine. Up to 60% of metabolites are excreted in urine and 20% in feces. |
| Half-life | Terminal elimination half-life is approximately 25 hours (range 20–30 hours), supporting once-daily dosing. Steady-state is achieved within 4–5 days. |
| Protein binding | Highly bound to plasma proteins (approximately 96–99%), primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 4.7 L/kg (range 2–8 L/kg), indicating extensive extravascular distribution and high tissue penetration. |
| Bioavailability | Absolute oral bioavailability is approximately 72% (range 60–85%) due to first-pass metabolism. |
| Onset of Action | Clinical antidepressant effects may be observed within 1–2 weeks, but full therapeutic response typically requires 4–8 weeks of daily oral dosing. |
| Duration of Action | Duration of action is approximately 24 hours due to the long half-life, allowing once-daily administration. Sustained response requires continued dosing. |
40 mg orally once daily initially, may increase to 20 mg twice daily or 40 mg once daily; maximum 40 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not recommended in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: maximum 20 mg/day; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dosing. |
| Geriatric use | No specific dose adjustment, but elderly patients may be more sensitive; start at lower end of dosing range and titrate slowly; monitor for hyponatremia and QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome Can cause diarrhea and insomnia.
| Breastfeeding | Unknown if excreted in human breast milk; no available M/P ratio. Due to potential for serious adverse reactions (serotonin toxicity) in breastfed infants, discontinue drug or nursing, considering importance of drug to mother. |
| Teratogenic Risk | Pregnancy category C. First trimester: Data insufficient to assess risk of major malformations; animal studies show increased fetal death and developmental delays at supratherapeutic doses. Second/third trimester: Risk of serotonin syndrome in neonate and persistent pulmonary hypertension of the newborn (PPHN). Late third trimester: Potential for withdrawal symptoms including irritability, feeding difficulties, respiratory distress. |
■ FDA Black Box Warning
Suicidal thoughts and behaviors: Antidepressants, including vilazodone, increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Short-term studies did not show an increase in suicidality with antidepressants compared to placebo in patients over age 24; a reduction was seen in patients 65 and older. Families and caregivers should be advised of the need for close monitoring.
| Common Effects | Diarrhea |
| Serious Effects |
["Concomitant use with MAOIs or within 14 days of MAOI therapy (risk of serotonin syndrome)","Concomitant use with linezolid or intravenous methylene blue","Hypersensitivity to vilazodone or any component of the formulation"]
| Precautions | ["Suicidal ideation and behavior","Serotonin syndrome","Activation of mania/hypomania","Seizures: Use with caution in patients with seizure disorders","Angle-closure glaucoma","Hyponatremia (especially in elderly)","Abnormal bleeding: Increased risk with NSAIDs, aspirin, anticoagulants","Sexual dysfunction","Discontinuation syndrome","QT prolongation: Caution in patients with risk factors or concurrent QT-prolonging drugs"] |
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| Fetal Monitoring | Monitor for serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability) in mother. For neonate: observe for PPHN, respiratory distress, feeding intolerance, irritability, and withdrawal signs. Consider fetal ultrasound if exposed in first trimester. |
| Fertility Effects | In animal studies, vilazodone did not impair fertility at exposures ≥2 times the maximum recommended human dose. Human data lacking, but SSRIs/SNRIs may reduce sperm quality or cause sexual dysfunction; clinical significance for fertility unknown. |