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

Trintellix (Vortioxetine) Treatment Protocol for Major Depressive Disorder

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

Initial Dosing Strategy

• Begin at 10 mg once daily as the recommended starting dose, administered orally without food restrictions 1
• Titrate to 20 mg daily as the target therapeutic dose once tolerance is established 1
• Reduce to 5 mg daily only for patients experiencing intolerable adverse effects at higher doses 1
• Vortioxetine demonstrates dose-proportional, linear pharmacokinetics with steady-state achieved within 2 weeks 2

Special Population Dosing

• CYP2D6 poor metabolizers require dose reduction: Maximum dose is 10 mg daily in known poor metabolizers 1
• No dose adjustment needed for sex, age, race, body size, renal impairment, or hepatic dysfunction 2
• Not approved for pediatric patients 1

Drug Interactions Requiring Dose Modification

• Strong CYP2D6 inhibitors (e.g., bupropion): Reduce vortioxetine dose by half when coadministered 1
• Strong CYP inducers (e.g., rifampin): Consider increasing vortioxetine dose up to 3 times the original dose when coadministered for more than 14 days, not exceeding maximum recommended dose 1
• Most other drug interactions do not require dose adjustments 2

Treatment Duration and Monitoring

• Continue treatment for 9-12 months minimum after achieving satisfactory response 3
• Monitor closely during weeks 1-2 after initiation, then throughout treatment for response and adverse effects 1
• Assess for suicidal ideation especially during the first 1-2 months, as vortioxetine carries a black box warning for increased suicidal thinking in young adults 1
• Modify treatment if inadequate response is not achieved within 6-8 weeks 3

Discontinuation Protocol

• Abrupt discontinuation is possible but not preferred 1
• For doses of 15-20 mg daily: Taper to 10 mg daily for one week before full discontinuation when feasible 1

Comparative Positioning

• Vortioxetine is equivalent to other second-generation antidepressants in efficacy for first-line treatment of MDD 3
• The American College of Physicians recommends selecting between cognitive behavioral therapy or second-generation antidepressants (including vortioxetine) based on patient preference, adverse effect profiles, cost, and accessibility 3
• Network meta-analyses show similar symptomatic benefits across different second-generation antidepressants, with low certainty of evidence for most direct comparisons 3

Common Adverse Effects to Monitor

• Nausea is the most common adverse effect (≥10% incidence) 4
• Headache occurs frequently (≥10% incidence) 4
• Constipation and vomiting occur in ≥5% of patients at twice the rate of placebo 1
• Sexual dysfunction may occur, particularly at the 20 mg dose 1, 5
• Bleeding risk increases when combined with NSAIDs, aspirin, antiplatelet drugs, or anticoagulants 1
• Serotonin syndrome risk when combined with other serotonergic agents 1
• Hyponatremia/SIADH can occur 1

Critical Safety Contraindications

• Absolute contraindication with MAOIs: Do not use within 21 days of stopping vortioxetine or within 14 days of stopping an MAOI 1
• Do not initiate in patients receiving linezolid or intravenous methylene blue 1
• Screen for bipolar disorder before initiating, as vortioxetine may precipitate mania/hypomania 1
• Caution in untreated narrow-angle glaucoma due to risk of angle closure 1

Unique Clinical Advantages

• Vortioxetine demonstrates independent cognitive benefits beyond depression symptom improvement, with significant improvements on objective measures (Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test) covering executive function, attention, processing speed, learning, and memory 6, 5
• Long-term treatment (52 weeks) shows sustained tolerability with continued improvement in depression, anxiety, and functional outcomes 4
• The multimodal mechanism (SERT inhibition plus 5-HT3/5-HT7 antagonism and 5-HT1A agonism) may contribute to improved outcomes in patients with cognitive dysfunction 7, 5