Starting Dose of Trintellix (Vortioxetine)
The recommended starting dose of Trintellix (vortioxetine) is 10 mg administered orally once daily without regard to meals. 1
Dosing Guidelines
Trintellix dosing follows a specific protocol:
- Initial dose: 10 mg once daily
- Titration: The dose should be increased to 20 mg/day as tolerated
- Lower dose option: 5 mg/day can be considered for patients who do not tolerate higher doses
- Special populations: Maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers
Pharmacokinetic Considerations
Vortioxetine has favorable pharmacokinetic properties that support once-daily dosing:
- Linear and dose-proportional pharmacokinetics
- Mean terminal half-life of approximately 66 hours
- Steady-state plasma concentrations generally achieved within 2 weeks
- Mean absolute oral bioavailability of 75%
- No food effect on pharmacokinetics 2
Efficacy Across Dose Range
Clinical evidence supports the efficacy of multiple vortioxetine doses:
- A randomized withdrawal study demonstrated that vortioxetine at 5 mg (19.3% relapse rate), 10 mg (17.9% relapse rate), and 20 mg (17.4% relapse rate) all significantly reduced relapse risk compared to placebo (32.5% relapse rate) 3
- The multimodal mechanism of action involves both serotonin reuptake inhibition and direct modulation of multiple serotonin receptors (5-HT3, 5-HT7, 5-HT1D, and 5-HT1B) 4
Tolerability and Side Effects
Common side effects to monitor when initiating Trintellix include:
- Nausea (20.9-31.2%)
- Vomiting (2.9-6.5%)
- Constipation (incidence ≥5% and at least twice the rate of placebo) 1, 5
The side effect profile is generally favorable compared to other antidepressants:
- Low incidence of insomnia (2.0-5.1% vs 4.0% for placebo)
- Low incidence of sexual dysfunction (1.6-1.8% vs 1.0% for placebo)
- Minimal effect on body weight, heart rate, or blood pressure 5
Special Considerations
- Discontinuation: Trintellix can be discontinued abruptly. However, it's 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
- Drug interactions: Dose reduction by half is recommended when coadministered with strong CYP2D6 inhibitors 1
- Contraindications: Hypersensitivity to vortioxetine and concomitant use of MAOIs 1
Clinical Pearls
- Vortioxetine has shown efficacy in treating both depressive and anxiety symptoms
- The drug's clinical action is believed to be mediated by selective blockade of serotonin reuptake and direct modulation of serotonin receptor activity
- Vortioxetine has demonstrated a favorable tolerability profile with lower risk of common antidepressant-induced adverse effects compared to some other antidepressants 4