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. |
| Molecular Weight | 441.93 |
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 | Limited data; potential risk of neural tube defects? Use only if benefit outweighs risk. |
| 2nd trimester | No evidence of major malformations; monitor for maternal weight gain and fetal growth. |
| 3rd trimester | Risk of neonatal serotonin syndrome and withdrawal symptoms; avoid near term. |
Clinical note
MAOIs can cause serotonin syndrome Can cause diarrhea and insomnia.
| Placental transfer | Crosses placenta in animals; human data limited but expected to cross due to molecular weight. |
| Breastfeeding | Vilazodone is excreted into breast milk in low amounts; monitor infant for irritability, poor feeding, and sedation. |
| Lactation Rating |
■ 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 MAOIsHypersensitivity to vilazodone or any excipient
| 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 |
Loading safety data…
| L3 |
| 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. |
| 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. |
| Food/Dietary | Must be administered with food to achieve adequate bioavailability. Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition, which may increase vilazodone levels. Alcohol may potentiate CNS depression and should be avoided. |
| Clinical Pearls | Vilazodone is a serotonin partial agonist and reuptake inhibitor (SPARI). Unlike SSRIs, it has a fast onset of action (1-2 weeks). Must be taken with food to achieve therapeutic concentrations; without food, AUC decreases by 50%. Common side effects include diarrhea (more frequent than with SSRIs), nausea, and insomnia. Avoid use in patients with bipolar disorder as it may precipitate manic episodes. No significant QTc prolongation in clinical studies. Dose titration: start at 10 mg daily for 7 days, then increase to 20 mg daily; further increase to 40 mg daily after at least 7 days based on response and tolerability. |
| Patient Advice | Take this medication with food, preferably a meal, to ensure it works properly. · It may take 1-2 weeks to feel improvement in mood; full benefit may take 4-8 weeks. · Do not stop abruptly; discuss with your doctor to avoid withdrawal symptoms. · Avoid alcohol while taking vilazodone. · Contact your doctor if you experience worsening depression, suicidal thoughts, or unusual behavior changes. · Common side effects include diarrhea, nausea, vomiting, insomnia, and dizziness; report if severe. · Inform all healthcare providers you are taking this medication. |