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

Trintellix (Vortioxetine) for Major Depressive Disorder

Recommended Dosing

Start vortioxetine at 10 mg once daily orally without regard to meals, then increase to 20 mg daily as tolerated; consider 5 mg daily only for patients who cannot tolerate higher doses. 1

• The FDA-approved starting dose is 10 mg once daily, which should be increased to the target dose of 20 mg daily as tolerated 1
• The 5 mg dose is reserved specifically for patients who do not tolerate higher doses 1
• Vortioxetine demonstrates dose-dependent efficacy, with 20 mg daily being the effective dose in US clinical trials 2
• No food restrictions apply—administer without regard to meals 1

Treatment Monitoring

Begin monitoring within 1-2 weeks of initiation, focusing on suicidal ideation, agitation, irritability, and unusual behavioral changes, as suicide risk peaks during the first 1-2 months of treatment. 3, 4, 5

• Assess therapeutic response and adverse effects at regular intervals starting within 1-2 weeks 3, 4
• The FDA mandates close monitoring for increased suicidal thoughts and behaviors, particularly in the first 1-2 months when risk is highest 3, 5
• Watch specifically for emergence of agitation, irritability, or unusual behavioral changes as indicators of worsening depression 3, 5

Treatment Response Timeline

If inadequate response occurs after 6-8 weeks, modify treatment—do not continue ineffective therapy. 3, 4, 5

• Response rates to antidepressant therapy may be as low as 50%, making treatment modification common 3
• The 6-8 week timeframe is the standard window for assessing adequate response to pharmacotherapy 3, 4
• Insufficient evidence exists to prefer one second-generation antidepressant over another as second-line therapy 3

Treatment Duration

Continue vortioxetine for 4-9 months after achieving satisfactory response in first-episode major depressive disorder; patients with 2 or more previous episodes require years to lifelong therapy. 3, 4, 5

• The 4-9 month continuation phase prevents relapse (defined as symptom return during acute or continuation phases) 3
• Patients with recurrent depression (≥2 episodes) benefit from extended maintenance therapy to prevent recurrence (new distinct episodes) 3, 4
• In the RESET study, all vortioxetine doses (5,10, and 20 mg) effectively prevented relapse compared to placebo (17.4-19.3% vs 32.5% relapse rates over 28 weeks) 6

Discontinuation Strategy

Vortioxetine can be discontinued abruptly, but for doses of 15-20 mg daily, reduce to 10 mg daily for one week before full discontinuation to minimize withdrawal symptoms. 1, 2

• Unlike many antidepressants, vortioxetine does not require prolonged tapering 1
• The one-week step-down from higher doses (15-20 mg) to 10 mg represents a practical compromise to avoid potential withdrawal effects 1, 2

Dose Adjustments for Drug Interactions

Reduce vortioxetine dose by half when coadministering strong CYP2D6 inhibitors (e.g., bupropion); consider tripling the dose (not exceeding 3 times original) when coadministering strong CYP inducers for more than 14 days. 1

• The maximum recommended dose is 10 mg daily in known CYP2D6 poor metabolizers 1, 2
• Strong CYP2D6 inhibitors significantly increase vortioxetine exposure, necessitating dose reduction 1, 7
• Rifampin and other broad CYP inducers decrease vortioxetine levels, potentially requiring dose escalation 1, 7
• No dose adjustment needed for age, sex, race, body size, or mild-to-moderate renal/hepatic impairment 7, 2

Common Adverse Effects

Nausea is the most common adverse effect (dose-dependent), followed by headache and constipation; monitor for bleeding risk when combined with antiplatelet agents or anticoagulants. 1, 8, 2

• Nausea occurs most frequently and demonstrates dose-dependent severity 1, 8, 2
• The adverse event profile resembles other SSRIs, with generally mild-to-moderate severity 8, 2, 6
• Concomitant use with aspirin, NSAIDs, antiplatelet drugs, or anticoagulants increases bleeding risk 1
• Screen for bipolar disorder before initiating treatment due to risk of manic activation 1
• Monitor for hyponatremia, particularly SIADH, and angle-closure glaucoma in susceptible patients 1

Clinical Pearls

• Vortioxetine's terminal half-life of approximately 66 hours means steady-state concentrations are achieved within 2 weeks 7
• The drug demonstrates linear, dose-proportional pharmacokinetics with 75% oral bioavailability 7
• Long-term treatment (52 weeks) shows continued improvement in depression and anxiety symptoms with acceptable tolerability 8
• For patients achieving remission at 10 mg daily, all doses (5,10,20 mg) effectively prevent relapse 6