VORTIOXETINE HYDROBROMIDE
Clinical safety rating: safe
MAOIs can cause serotonin syndrome Can cause nausea and increased risk of bleeding.
Vortioxetine is a serotonin modulator and stimulator. It acts as a 5-HT3 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist, and inhibits the serotonin transporter (SERT), leading to increased serotonin concentrations in the synaptic cleft.
| Metabolism | Extensively metabolized primarily via CYP2D6, with minor contributions from CYP3A4, CYP2C9, CYP2C19, and CYP2A6. The major metabolite is an inactive carboxylic acid. |
| Excretion | Renal: <1% unchanged, fecal: primarily as metabolites (~59% fecal, ~26% urinary as conjugated metabolites) |
| Half-life | Terminal elimination half-life: ~66 hours (range 59-72 hours), allowing once-daily dosing. |
| Protein binding | ~98-99% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent Vd: ~2600 L (approximately 37 L/kg for a 70 kg individual), indicating extensive extravascular distribution. |
| Bioavailability | Oral: ~75% (range 73-83%), unaffected by food. |
| Onset of Action | Oral: clinical improvement (antidepressant effect) may begin within 1-2 weeks, with full effect often seen by 4-6 weeks. |
| Duration of Action | Due to long half-life, therapeutic effects persist for several days after discontinuation; steady state reached in ~2 weeks. |
| Molecular Weight | 298.4 |
10 mg orally once daily; may increase to 20 mg once daily. Maximum 20 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min. Not recommended for GFR <15 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 10 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Not approved for patients <18 years of age. |
| Geriatric use | The recommended dose is 10 mg once daily; maximum dose 20 mg once daily, with careful titration due to increased sensitivity. |
| 1st trimester | Limited human data; animal studies showed no teratogenicity at clinically relevant doses, but risks cannot be excluded. Use only if potential benefit justifies potential risk. |
| 2nd trimester | Limited human data; consider maternal mental health risks of untreated depression. Monitor for adverse effects. |
| 3rd trimester | Risk of persistent pulmonary hypertension of the newborn (PPHN) and neonatal withdrawal syndrome (irritability, tachypnea, poor feeding). Use only if clearly needed. |
Clinical note
MAOIs can cause serotonin syndrome Can cause nausea and increased risk of bleeding.
| FDA category | Animal |
| Placental transfer | Vortioxetine crosses the placenta; human data limited but molecular weight and lipophilicity suggest significant transfer. Animal studies confirm placental transfer. |
■ FDA Black Box Warning
Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Common Effects | Nausea |
| Serious Effects |
Hypersensitivity to vortioxetine or any excipientConcomitant use with MAOIs (risk of serotonin syndrome)Concomitant use with linezolid or intravenous methylene blue
| Precautions | Suicidal thoughts and behaviors in pediatric and young adult patients, Serotonin syndrome or neuroleptic malignant syndrome-like reactions, Activation of mania/hypomania in patients with bipolar disorder, Angle-closure glaucoma (pupillary dilation), Hyponatremia (especially in elderly or volume-depleted patients), Abnormal bleeding (increased risk with NSAIDs, aspirin, anticoagulants), Sexual dysfunction, Potential for cognitive and motor impairment |
| Food/Dietary |
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| Breastfeeding |
| Vortioxetine is excreted into human milk; infant exposure estimated at 1-2% of maternal weight-adjusted dose. No adverse effects reported in small studies. Monitor infant for sedation, poor feeding, or irritability. Benefit of breastfeeding generally outweighs risk. |
| Lactation Rating | L2 (Limited data - possibly compatible) |
| Teratogenic Risk | Pregnancy category C. First trimester: limited human data; animal studies show no teratogenicity at exposures up to 20 times MRHD, but increased fetal mortality and delayed ossification at maternally toxic doses. Second/third trimester: neonatal adaptation syndrome (respiratory distress, feeding difficulties, jitteriness) reported with late third trimester use. Risk of persistent pulmonary hypertension of the newborn (PPHN) is not established. |
| Fetal Monitoring | Monitor maternal mood and suicidal ideation throughout pregnancy. Assess fetal growth (ultrasound) if exposure in third trimester. Observe neonate for signs of toxicity or withdrawal syndrome for 48-72 hours after delivery. |
| Fertility Effects | No human data on fertility effects. Animal studies show no impairment of fertility or reproductive performance in rats at doses up to 400 mg/kg (≥20 times MRHD). |
| No significant food interactions. Grapefruit juice may modestly increase vortioxetine exposure (weak CYP3A4 inhibition) but not clinically relevant. Avoid excessive alcohol intake due to additive CNS depression. |
| Clinical Pearls | Vortioxetine is a multimodal antidepressant with serotonin reuptake inhibition and receptor modulation (5-HT1A agonist, 5-HT1B partial agonist, 5-HT3 and 5-HT7 antagonist). It has a favorable cognitive profile, particularly in domains of processing speed, learning, and memory. No significant QTc prolongation at therapeutic doses; but caution in hepatic impairment (Child-Pugh C: dose ≤10 mg/day). Onset of therapeutic effect may be delayed (2–4 weeks). Taper when discontinuing to avoid discontinuation syndrome. Contraindicated with MAOIs (including linezolid, methylene blue); allow 2-week washout. Dose adjustments needed in poor CYP2D6 metabolizers (reduce dose by half). |
| Patient Advice | Take once daily with or without food at roughly the same time each day. · Do not crush, chew, or split the tablet; swallow whole. · It may take several weeks to feel the full benefit; do not stop taking without consulting your doctor. · Common side effects include nausea, vomiting, constipation, and dizziness. Nausea often improves with continued use. · Avoid alcohol and grapefruit juice (may alter drug levels). · Contact your doctor immediately if you experience severe headache, confusion, or vision changes (signs of serotonin syndrome or hyponatremia). · Do not drive or operate heavy machinery until you know how this medication affects you, as dizziness and somnolence may occur. · Inform all healthcare providers you are taking vortioxetine. |