VORTIOXETINE
Clinical safety rating: safe
Animal studies have demonstrated safety
Vortioxetine is a multimodal antidepressant that acts as a serotonin reuptake inhibitor (SRI), 5-HT1A receptor agonist, 5-HT1B receptor partial agonist, and antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors. This complex pharmacology enhances serotonergic activity in specific brain regions while modulating other neurotransmitter systems.
| Metabolism | Primarily metabolized by CYP2D6, with minor contributions from CYP3A4 and CYP2C9. Also undergoes oxidation followed by glucuronide conjugation. |
| Excretion | Vortioxetine is extensively metabolized, and the majority of the dose is excreted in urine (approximately 59%) as metabolites, with about 26% excreted in feces as unchanged drug or metabolites. Renal excretion of unchanged vortioxetine is negligible (<1%). |
| Half-life | The terminal elimination half-life of vortioxetine is approximately 66 hours (range 59–75 hours), supporting once-daily dosing. Steady-state concentrations are achieved within 14 days. |
| Protein binding | Approximately 98–99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The apparent volume of distribution is approximately 2600 L (or ~37 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 75% (range 60–90%) and is not significantly affected by food. |
| Onset of Action | Therapeutic effects (antidepressant response) are typically observed within 2–4 weeks of starting oral therapy, although some improvement may be seen as early as 2 weeks. No other routes are clinically available. |
| Duration of Action | Due to its long half-life, the pharmacodynamic effect persists for several days after discontinuation; gradual dose tapering is recommended to avoid withdrawal symptoms. |
10 mg orally once daily; may increase to 20 mg once daily. Maximum dose 20 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR >= 30 mL/min). Insufficient data for severe renal impairment (eGFR < 30 mL/min); use with caution. |
| Liver impairment | Child-Pugh A (mild): no dose adjustment. Child-Pugh B (moderate): maximum dose 10 mg once daily. Child-Pugh C (severe): not recommended. |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No dose adjustment required based solely on age; consider lower starting dose of 5 mg once daily due to increased sensitivity and potential for hyponatremia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome Can cause nausea and increased risk of bleeding.
| Breastfeeding | Vortioxetine is excreted into breast milk in low concentrations; M/P ratio approximately 0.2. Estimated relative infant dose is about 1-2% of maternal weight-adjusted dose. Limited human data suggest no adverse effects in breastfed infants, but caution is advised. Monitor infant for drowsiness, poor feeding, and weight gain. |
| Teratogenic Risk | Pregnancy category not formally assigned; data limited. Animal studies show no major teratogenicity at clinically relevant doses, but fetal exposure occurs. First trimester: risk of major malformations not significantly increased based on small human studies; second and third trimesters: potential risk of poor neonatal adaptation syndrome including respiratory distress, feeding difficulties, irritability, and muscle tone abnormalities due to serotonergic effects. |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor closely for clinical worsening, suicidality, or unusual changes in behavior.
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to vortioxetine or any excipient","Concomitant use with MAOIs (including linezolid and IV methylene blue)","Concomitant use with serotonergic drugs (risk of serotonin syndrome)"]
| Precautions | ["Activation of mania/hypomania","Hyponatremia (SIADH)","Serotonin syndrome","Angle-closure glaucoma","Sexual dysfunction","Increased bleeding risk (especially with NSAIDs/anticoagulants)","Cognitive and motor impairment"] |
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| Fetal Monitoring | Monitor for signs of serotonin syndrome (e.g., hyperthermia, rigidity, myoclonus) in mother. Assess fetal growth via ultrasound. Monitor neonate for poor neonatal adaptation syndrome (including respiratory distress, feeding difficulties, irritability, tremor, and hypotonia) for 2-4 days postpartum. |
| Fertility Effects | No specific human studies on fertility; animal studies showed no significant impairment of fertility at exposures up to 2.5 times the maximum recommended human dose. However, hyperprolactinemia may occur with SSRIs, potentially affecting gonadal function, though not specifically reported for vortioxetine. |