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

Recommended Treatment and Dosing for Trintellix (Vortioxetine) in Adults with Major Depressive Disorder

The recommended treatment for adults with major depressive disorder (MDD) using Trintellix (vortioxetine) is to start with 10 mg administered orally once daily without regard to meals, then increase to 20 mg/day as tolerated, with consideration of 5 mg/day for patients who cannot tolerate higher doses. 1

Initial Dosing and Titration

• The FDA-approved starting dose for Trintellix is 10 mg once daily, which can be taken with or without food 1
• After initial dosing, the dose should be increased to 20 mg/day as tolerated for optimal therapeutic effect 1
• For patients who cannot tolerate higher doses, a lower dose of 5 mg/day may be considered 1
• The maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers 1

Treatment Duration and Phases

• Treatment of MDD occurs in three phases: acute (6-12 weeks), continuation (4-9 months), and maintenance (≥1 year) 2
• After achieving remission in the acute phase, treatment should be continued for 4-9 months for patients with a first episode of MDD 2
• For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 2
• Long-term treatment with vortioxetine has been shown to be well-tolerated in studies up to 52 weeks 3

Dose Adjustments in Special Populations

• No clinically relevant differences in vortioxetine exposure have been observed based on sex, age, race, body size, or renal function 4
• Dose adjustment is only recommended for CYP2D6 poor metabolizers (maximum 10 mg/day) 1, 4
• When co-administered with strong CYP2D6 inhibitors (e.g., bupropion), the Trintellix dose should be reduced by half 1
• When co-administered with strong CYP inducers (e.g., rifampin) for more than 14 days, consider increasing the Trintellix dose, not exceeding 3 times the original dose 1

Discontinuation

• Trintellix can be discontinued abruptly, but 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
• The long half-life of vortioxetine (approximately 66 hours) may help minimize discontinuation symptoms 4

Efficacy and Clinical Considerations

• Vortioxetine has demonstrated efficacy at doses of 10 mg and 20 mg in reducing depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) 5
• The 20 mg dose has shown statistically significant separation from placebo in reducing MADRS total scores at 8 weeks 5
• All doses (5 mg, 10 mg, and 20 mg) have demonstrated efficacy in relapse prevention for patients who achieved remission on vortioxetine 10 mg daily 6
• In a recent study comparing vortioxetine to desvenlafaxine, vortioxetine showed similar response rates (43.4% vs. 36.7%) and remission rates (18.0% vs. 20.3%) 2

Safety and Monitoring

• Regular assessment of patient status, therapeutic response, and adverse effects should begin within 1-2 weeks of treatment initiation 2
• Treatment should be modified if the patient does not have an adequate response within 6-8 weeks of initiation 2
• The most common adverse events (≥5% and at least twice the rate of placebo) are nausea, constipation, and vomiting 1
• Other common adverse events include headache 3
• Monitor for signs of serotonin syndrome, especially when combined with other serotonergic agents 1
• Increased risk of bleeding may occur, particularly when used with aspirin, NSAIDs, antiplatelet drugs, or anticoagulants 1
• As with other antidepressants, monitor for activation of mania/hypomania and screen patients for bipolar disorder 1

Pharmacological Properties

• Vortioxetine has a multimodal mechanism of action that includes inhibition of the serotonin transporter (SERT) and modulation of several serotonin receptors (5-HT3, 5-HT1A, 5-HT7) 7
• The mean absolute oral bioavailability is 75% with no significant food effect on pharmacokinetics 4
• Steady-state plasma concentrations are generally achieved within 2 weeks of dosing 4
• The mean terminal half-life is approximately 66 hours 4