Maximum Recommended Dose of Trintellix (Vortioxetine)
The maximum recommended dose of Trintellix (vortioxetine) is 20 mg once daily.
Dosing Information
Trintellix is an antidepressant medication with a multimodal mechanism of action, primarily used in the treatment of major depressive disorder (MDD). The dosing recommendations are as follows:
- Starting dose: 10 mg once daily
- Dose range: 5-20 mg once daily
- Maximum approved dose: 20 mg once daily
Clinical Evidence and Considerations
The maximum dose of 20 mg daily is established based on clinical trials demonstrating efficacy and safety at this dosage. While some research has explored supratherapeutic dosing (doses above the FDA-approved maximum), these higher doses are not officially recommended for routine clinical practice.
A 2022 study examined supratherapeutic doses of 30-40 mg/day in treatment-resistant depression, reporting relative tolerability and effectiveness 1. However, this practice remains investigational and outside standard clinical guidelines.
Special Populations and Dose Adjustments
CYP2D6 Poor Metabolizers
- Dose adjustment may be necessary for patients who are known CYP2D6 poor metabolizers, as vortioxetine is primarily metabolized by this enzyme 2
Concomitant Medications
- Strong CYP2D6 inhibitors (e.g., bupropion): Consider reducing the vortioxetine dose by half when co-administered 2
- Strong CYP inducers (e.g., rifampin): May require dose adjustment due to potential reduction in vortioxetine exposure 2
Safety and Tolerability
Vortioxetine is generally well-tolerated at doses up to the maximum recommended 20 mg daily. Common side effects include:
- Nausea (20.9-31.2%)
- Vomiting (2.9-6.5%)
- Diarrhea
- Dry mouth 3
The incidence of insomnia (2.0-5.1%) and sexual dysfunction (1.6-1.8%) with vortioxetine is relatively low compared to some other antidepressants 3.
Clinical Pearls
- Vortioxetine has a long half-life of approximately 66 hours, with steady-state plasma concentrations generally achieved within 2 weeks of dosing 2
- Food does not significantly affect the pharmacokinetics of vortioxetine 2
- Unlike some antidepressants, vortioxetine shows minimal effects on body weight, heart rate, or blood pressure 3
- Discontinuation symptoms following abrupt discontinuation are comparable to placebo, suggesting a potentially favorable discontinuation profile 3
Caution
While some clinicians may consider doses above 20 mg in treatment-resistant cases, this practice is not supported by FDA labeling and should be approached with caution, weighing potential benefits against increased risk of side effects.