What is the recommended dosage of vortioxetine (Brintellix) for adults with major depressive disorder?

Vortioxetine Dosage for Major Depressive Disorder in Adults

The recommended dosage of vortioxetine (Trintellix) for adults with major depressive disorder is to start with 10 mg once daily, then increase to 20 mg daily as tolerated, with a lower 5 mg daily dose available for patients who cannot tolerate higher doses. 1

Initial Dosing and Titration

• Start with 10 mg administered orally once daily without regard to meals 1, 2
• Increase to 20 mg/day as tolerated, which is the most effective dose demonstrated in US studies 1, 2
• For patients who cannot tolerate higher doses, consider 5 mg/day 1, 2
• Maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers 1, 3

Pharmacokinetic Considerations

• Vortioxetine has linear and dose-proportional pharmacokinetics 3
• Mean terminal half-life is approximately 66 hours 3
• Steady-state plasma concentrations are generally achieved within 2 weeks of dosing 3
• Mean absolute oral bioavailability is 75% 3
• No food effect on pharmacokinetics has been observed 3

Efficacy by Dose

• 20 mg/day showed the most consistent efficacy in US studies 2, 4
• In one pivotal study, the 20 mg dose significantly reduced Montgomery-Asberg Depression Rating Scale (MADRS) total score compared to placebo (p=0.002), while the 10 mg dose approached but did not reach statistical significance (p=0.058) 4
• Response rates (≥50% decrease in MADRS score) were 28.4% for placebo, 33.8% for 10 mg, and 39.2% for 20 mg, with only the 20 mg dose showing statistically significant separation from placebo (p=0.044) 4

Special Populations

• No dose adjustment needed based on age, gender, or presence of renal or mild to moderate hepatic impairment 2, 3
• Reduce dose by half when co-administered with strong CYP2D6 inhibitors (e.g., bupropion) 1, 3
• Consider dose increase when co-administered with strong CYP inducers (e.g., rifampin) for more than 14 days, not exceeding 3 times the original dose 1

Discontinuation

• Vortioxetine can be discontinued abruptly 1
• 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 to avoid potential withdrawal symptoms 1, 2

Adverse Effects

• Most common adverse events are nausea (dose-dependent), constipation, and vomiting 1, 4
• Adverse event profile is similar to that of other selective serotonin reuptake inhibitors (SSRIs) 2
• Monitor for serotonin syndrome, increased risk of bleeding, activation of mania/hypomania, and hyponatremia 1

Treatment Duration

• For a first episode of major depressive disorder, continue treatment for 4 to 9 months after a satisfactory response 5
• For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 5

Vortioxetine's unique multimodal mechanism of action (SERT inhibition plus modulation of several serotonin receptors) may provide benefits for both depressive symptoms and cognitive deficits in MDD patients 6, but this should not influence the dosing strategy outlined above.