What is the recommended dosing for Trintellix (vortioxetine)?

Trintellix (Vortioxetine) Dosing Recommendations

The recommended dosing for Trintellix (vortioxetine) is to start at 10 mg once daily, then increase to 20 mg once daily as tolerated, with 5 mg daily available for patients who cannot tolerate higher doses. 1

Initial Dosing and Titration

• Start with 10 mg administered orally once daily
• Can be taken without regard to meals (no food effect on pharmacokinetics) 2
• Increase to 20 mg/day as tolerated
• For patients who cannot tolerate higher doses, consider 5 mg/day

Special Populations and Considerations

CYP2D6 Poor Metabolizers

• Maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers 1
• Vortioxetine is metabolized primarily by cytochrome P450 enzymes 2

Drug Interactions

• Strong CYP2D6 inhibitors (e.g., bupropion): Reduce Trintellix dose by half 1
• Strong CYP inducers (e.g., rifampin): Consider dose increase when coadministered for more than 14 days. Maximum recommended dose should not exceed 3 times the original dose 1

No Dose Adjustments Required For:

• Age
• Gender
• Race
• Body size
• Renal function
• Mild to moderate hepatic impairment 2

Maintenance Therapy

• Effective maintenance doses range from 5-20 mg daily 3
• In a US-based study, all doses (5 mg, 10 mg, and 20 mg) were effective for relapse prevention in patients who achieved remission on 10 mg daily 3
• Time to relapse was longer and cumulative relapse rates were lower for all vortioxetine doses compared to placebo over 28 weeks 3

Discontinuation

• Trintellix can be discontinued abruptly
• However, it is recommended that doses of 15 mg/day or 20 mg/day be reduced to 10 mg/day for one week prior to full discontinuation if possible 1
• This tapering approach helps avoid potential withdrawal symptoms

Pharmacokinetic Considerations

• Linear and dose-proportional pharmacokinetics
• Mean terminal half-life of approximately 66 hours
• Steady-state plasma concentrations generally achieved within 2 weeks of dosing
• Mean absolute oral bioavailability of 75% 2

Common Side Effects

• Most common adverse reactions (incidence ≥5% and at least twice the rate of placebo):
  • Nausea (dose-dependent)
  • Constipation
  • Vomiting 1, 4

Clinical Pearls

• Vortioxetine has a multimodal mechanism of action, targeting multiple serotonin receptors (5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7) and the serotonin transporter 5
• The medication has shown efficacy in treating major depressive disorder with a favorable tolerability profile
• Vortioxetine has demonstrated positive effects on cognitive symptoms of major depressive episodes 5
• The long half-life (66 hours) may provide some forgiveness for occasional missed doses 2

Monitoring

• Monitor for signs of serotonin syndrome, especially when combined with other serotonergic agents 1
• Be alert for increased risk of bleeding, particularly when used with aspirin, NSAIDs, antiplatelet drugs, or anticoagulants 1
• Screen for bipolar disorder before initiating treatment due to risk of mania/hypomania activation 1