Generic Name

Vortioxetine

Brand Names

*Luvoxix* in some markets, generic *vortioxetine*) is a multimodal serotonin‑modulating antidepressant approved for major depressive disorder (MDD).

Mechanism

• Primary action: Selective serotonin reuptake inhibitor (SSRI) with high affinity for the serotonin transporter (SERT).
• Secondary actions:
• Agonist at *5‑HT₁A* receptors (enhances serotonergic neurotransmission).
• Partial agonist at *5‑HT₁B* receptors.
• Antagonist at *5‑HT₃, 5‑HT₁D, 5‑HT₂C,* and *5‑HT₂B* receptors.
• The combination of SERT inhibition and receptor modulation is thought to improve serotonergic tone and mitigate some SSRI‑associated side‑effects (e.g., gastrointestinal distress, sexual dysfunction).

Pharmacokinetics

• Absorption: Oral bioavailability ~27 % at 10 mg; absorption is dose‑dependent. Peak plasma levels reached ~3 h post‑dose.
• Distribution: Protein‑binding ~94 %; penetrates the blood–brain barrier efficiently.
• Metabolism: Primarily hepatic CYP2D6 and CYP3A4; minor metabolite is *norvortioxetine* (inactive).
• Elimination: 90 % renal excretion; half‑life ~66 h (steady‑state ~10 days).
• Drug interactions:
• Moderate inhibitors of CYP2D6 (e.g., fluconazole) can raise levels.
• Strong CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin) may alter exposure.
• Combined use with MAO‑Is is contraindicated.

Indications

• Major depressive disorder (MDD) in adults (≥18 yr).
• FDA‑approved adult dose range: 5 – 20 mg/day.

Contraindications

• Contraindicated: concomitant use with monoamine oxidase inhibitors (MAO‑Is).
• Warnings:
• Serotonin syndrome risk when combined with other serotonergic agents (e.g., other SSRIs, SNRIs, TCA, tramadol).
• QTc prolongation – monitor in patients with pre‑existing QT prolongation or arrhythmias, or when combined with other QT‑prolonging drugs.
• Age: No formal restriction, but evidence primarily in 18‑65 yr cohort.
• Pregnancy/Lactation: Limited data; weigh benefits vs. risks.

Dosing

• Starting dose: 5 mg orally once daily (no morning/evening preference).
• Maintenance/ titration: Increase weekly by 5 mg increments; maximum 20 mg/day.
• Titration schedule (example):
• Week 1: 5 mg/day
• Week 2: 10 mg/day
• Week 3: 15 mg/day (if needed)
• Week 4: 20 mg/day (if still inadequate)
• Adjustments:
• Reduce in severe hepatic impairment.
• Reduce if severe renal insufficiency (CrCl < 30 mL/min) or consider alternative therapy.
• Missed dose: Take as soon as remembered; skip if near next dose.
• Adjunctive therapy: Not routinely indicated.

Adverse Effects

• Common (≥5 %):
• Nausea, constipation, diarrhea, dry mouth, dizziness, headaches.
• Less common (1–5 %):
• Abdominal cramps, increased sweating, insomnia, sedation.
• Serious (≤1 %):
• Serotonin syndrome (hyperthermia, clonus, agitation).
• QTc prolongation (severe arrhythmia).
• Severe hepatotoxicity (rare).

Monitoring

• Baseline:
• ECG if possible (baseline QTc).
• Creatinine clearance, liver function tests.
• During therapy:
• Symptom improvement (e.g., HDRS/HAMD score changes).
• Liver enzymes every 3–4 months (or earlier if symptomatic).
• Renal function if dose adjustment required.
• Patient education: Recognize signs of serotonin syndrome (e.g., tremor, hyperreflexia).

Clinical Pearls

• Multimodal advantage: The antagonism at *5‑HT₃* and *5‑HT₂C* receptors may reduce nausea and sexual dysfunction, common barriers to adherence with typical SSRIs.
• Steady‑state attainment: Because of its long half‑life (~66 h), therapeutic effects usually emerge within 2–4 weeks; counsel patients accordingly.
• Drug–drug interaction insight: Co‑administration with *fluoxetine* or *paroxetine* (strong CYP2D6 inhibitors) can increase serum levels; consider lower starting dose or monitor.
• QTc risk mitigation: Use caution in patients on *tricyclic antidepressants* (e.g., amitriptyline) or *serotonergic opioids* (e.g., tramadol).
• Elderly and renal impairment: No dosage adjustment is required for mild CKD, but caution in severe CKD due to limited data.
• Mental status monitoring: As with all antidepressants, there is a potential for increased agitation or suicidality in adolescents and young adults; regular screening recommended.

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• Key take‑away: Vortioxetine is a uniquely multimodal SSRI with a favorable side‑effect profile, especially regarding sexual and gastrointestinal tolerability, making it an attractive first‑line option for adult MDD when adherence and tolerability are paramount.