Vortioxetine Treatment Regimen for Major Depressive Disorder
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.
Initial Dosing Strategy
- Begin with 10 mg once daily as the recommended starting dose, administered orally without regard to food 1, 2.
- Titrate to 20 mg daily as tolerated, as this represents the target therapeutic dose with increasing efficacy at higher doses 1, 3.
- Reserve 5 mg daily exclusively for patients who demonstrate intolerance to higher doses 1.
- Steady-state plasma concentrations are achieved within approximately 2 weeks of consistent dosing 2.
Monitoring and Response Assessment
- Assess patient status within 1-2 weeks of initiating therapy for therapeutic response, adverse effects, and emergence of suicidal thoughts or behaviors 4.
- Continue regular monitoring throughout the acute treatment phase, particularly during the first 1-2 months when suicide risk is highest 4.
- Evaluate treatment adequacy at 6-8 weeks: if inadequate response occurs, modify treatment strategy 4.
Treatment Duration
- Continue for 4-9 months after achieving satisfactory response in patients with a first episode of major depressive disorder 4.
- Extend treatment duration (potentially years to lifelong) for patients with 2 or more previous depressive episodes 4.
- Long-term treatment with vortioxetine 15-20 mg has demonstrated safety and tolerability over 52 weeks 5.
Discontinuation Protocol
- Vortioxetine can be discontinued abruptly without significant withdrawal symptoms 1.
- For doses of 15-20 mg daily, reduce to 10 mg daily for one week prior to full discontinuation when possible 1.
Special Populations and Dose Adjustments
CYP2D6 Poor Metabolizers
- Maximum dose is 10 mg daily in known CYP2D6 poor metabolizers 1.
- Reduce dose by half when coadministered with strong CYP2D6 inhibitors (e.g., bupropion) 1.
Strong CYP Inducers
- Consider dose increase when coadministered with strong CYP inducers (e.g., rifampin) for more than 14 days 1.
- Maximum dose should not exceed 3 times the original dose 1.
No Adjustment Required
- No dose adjustments needed based on age, sex, race, body size, renal function, or hepatic function 1, 2, 6.
Common Pitfalls and Safety Considerations
Adverse Effects
- Nausea is the most common adverse effect (≥10% incidence), typically transitory 1, 5, 3.
- Other common adverse effects include constipation, vomiting, and headache (≥5% incidence) 1, 5.
- Vortioxetine demonstrates minimal effects on weight gain and sexual dysfunction compared to other antidepressants 3.
Critical Safety Warnings
- Screen for bipolar disorder before initiating treatment to avoid activation of mania/hypomania 1.
- Monitor for serotonin syndrome, particularly when combined with other serotonergic agents 1.
- Assess bleeding risk when used concomitantly with NSAIDs, aspirin, antiplatelet drugs, or anticoagulants 1.
- Monitor for hyponatremia, especially in elderly patients or those at risk for SIADH 1.
Contraindications
- Absolute contraindication: hypersensitivity to vortioxetine or formulation components 1.
- Do not use with MAOIs intended to treat psychiatric disorders, or within 21 days of stopping vortioxetine 1.
- Do not start vortioxetine within 14 days of stopping an MAOI intended to treat psychiatric disorders 1.
- Avoid concurrent use with linezolid or intravenous methylene blue 1.
Comparative Effectiveness Context
- Vortioxetine functions as a second-generation antidepressant with multimodal activity (SERT inhibitor, 5-HT3/5-HT7 antagonist, 5-HT1A agonist) 7, 3.
- Evidence shows similar efficacy between switching to vortioxetine versus other second-generation antidepressants in patients with inadequate initial response 4.
- Selection among second-generation antidepressants should be based on adverse effect profiles, cost, and patient preferences, as efficacy differences are not established 4.