What is the recommended treatment and dosage for major depressive disorder with Trintellix (vortioxetine)?

Trintellix (Vortioxetine) Treatment for Major Depressive Disorder

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

Dosing Recommendations

• The FDA-approved starting dose is 10 mg administered orally once daily without regard to meals 1
• Dose should be increased to 20 mg/day as tolerated for optimal efficacy 1, 2
• Consider 5 mg/day for patients who do not tolerate higher doses 1
• Maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers 1, 3
• Trintellix can be discontinued abruptly, but for doses of 15-20 mg/day, it's recommended to reduce to 10 mg/day for one week prior to full discontinuation 1

Efficacy and Dose Selection

• Vortioxetine was effective in treating MDD in the United States at a dose of 20 mg/day in clinical trials 2
• All doses (5 mg, 10 mg, and 20 mg) have demonstrated efficacy in preventing relapse of depression compared to placebo 4
• The 10 mg starting dose balances efficacy with tolerability for most patients 2
• Pharmacokinetics are linear and dose-proportional, with steady-state plasma concentrations generally achieved within 2 weeks 3

Treatment Duration

• For patients with a first episode of MDD who achieve remission, continue treatment for 4-9 months after symptom resolution 5, 6
• For patients with 2 or more previous depressive episodes, longer duration therapy (years to lifelong) may be beneficial due to higher risk of recurrence 5, 6
• Maintenance studies have shown that vortioxetine at doses of 5-20 mg/day effectively prevents relapse compared to placebo 4

Monitoring and Follow-up

• Assess patient status, therapeutic response, and adverse effects regularly beginning within 1-2 weeks of treatment initiation 5, 6
• Monitor closely for increases in suicidal thoughts and behaviors, especially during the first 1-2 months of treatment 5, 1
• If adequate response is not achieved within 6-8 weeks of initiating therapy, modify treatment 5
• Evaluate for emergence of agitation, irritability, or unusual changes in behavior that could indicate worsening depression 5

Adverse Effects

• Most common adverse events (≥5% and at least twice the rate of placebo) are nausea, constipation, and vomiting 1
• Nausea is the most common adverse event and is dose-dependent 2
• Long-term treatment with vortioxetine (15-20 mg) has been shown to be well-tolerated in 52-week extension studies 7
• Sexual dysfunction may occur but appears to have a different profile compared to some other SSRIs 2

Special Considerations

• No dose adjustment needed based on age, gender, or the presence of renal or mild to moderate hepatic impairment 3, 2
• Reduce Trintellix dose by half when co-administered with strong CYP2D6 inhibitors like bupropion 1
• Consider dose increase when co-administered with strong CYP inducers like rifampin for more than 14 days (maximum recommended dose should not exceed 3 times the original dose) 1
• Contraindicated with MAOIs: Do not use MAOIs within 21 days of stopping Trintellix, and do not start Trintellix within 14 days of stopping an MAOI 1

Clinical Pitfalls to Avoid

• Don't assume that initial improvement means treatment can be discontinued early; premature discontinuation increases relapse risk 6
• Don't overlook the need to reassess treatment if no improvement is seen after 6-8 weeks of therapy 5
• Be aware of potential increased risk of bleeding when used with aspirin, NSAIDs, warfarin, or other drugs affecting coagulation 1
• Monitor for signs of serotonin syndrome, especially when combined with other serotonergic agents 1