Brintellix (Vortioxetine) for Major Depressive Disorder
Recommended Dosage
Start vortioxetine at 10 mg orally once daily, then increase to 20 mg daily as tolerated for optimal efficacy. 1
Dosing Algorithm
- Initial dose: 10 mg once daily, taken without regard to meals 1
- Target dose: Increase to 20 mg daily as tolerated, as this dose demonstrated superior efficacy in reducing depressive symptoms (mean MADRS reduction of -14.41 vs -10.77 for placebo, p=0.002) 2
- Lower dose option: Consider 5 mg daily only for patients who cannot tolerate higher doses 1
- Maximum dose: 10 mg daily in known CYP2D6 poor metabolizers 1
Special Dosing Considerations
Reduce dose by half when co-administering strong CYP2D6 inhibitors (such as bupropion), as vortioxetine is primarily metabolized by CYP2D6 enzymes 1, 3
Consider dose increase up to 3 times the original dose (not exceeding maximum recommended) when co-administering strong CYP inducers (such as rifampin) for more than 14 days 1
Treatment Duration
Continue treatment for 4 to 9 months after achieving satisfactory response for a first depressive episode. 4
For patients with 2 or more prior episodes, maintain treatment for an even longer duration to prevent relapse, as recurrent MDD carries higher relapse risk 4
Relapse Prevention Data
All three maintenance doses (5 mg, 10 mg, and 20 mg) significantly reduced relapse rates compared to placebo over 28 weeks in patients who achieved remission on 10 mg:
- Vortioxetine 5 mg: 19.3% relapse rate
- Vortioxetine 10 mg: 17.9% relapse rate
- Vortioxetine 20 mg: 17.4% relapse rate
- Placebo: 32.5% relapse rate (p<0.05 for all comparisons) 5
Discontinuation Approach
For doses of 15 mg or 20 mg daily, taper to 10 mg daily for one week before full discontinuation when possible. 1
Vortioxetine can be discontinued abruptly without significant withdrawal symptoms, but gradual taper from higher doses minimizes potential discontinuation effects 1
Safety Profile
Common Adverse Events (≥5% incidence)
The most frequent side effects are nausea, constipation, and vomiting, though these are generally mild-to-moderate in severity 1
In long-term treatment (52 weeks), nausea and headache were the most common adverse events (≥10%), with only 10.7% of patients withdrawing due to adverse effects 6
Critical Safety Warnings
Do not use with MAOIs: Contraindicated within 14 days of stopping an MAOI or within 21 days after stopping vortioxetine 1
Monitor for serotonin syndrome when co-administered with other serotonergic agents, though risk also exists with vortioxetine alone 1
Increased bleeding risk when combined with aspirin, NSAIDs, antiplatelet drugs, warfarin, or other anticoagulants 1
Screen for bipolar disorder before initiating treatment, as vortioxetine may activate mania/hypomania 1
Monitor for suicidal thoughts and behaviors, particularly in young adults, as all antidepressants carry this black box warning 1
Clinical Context
Vortioxetine is classified as a second-generation antidepressant with multimodal activity, functioning as a serotonin transporter inhibitor, 5-HT3 and 5-HT7 receptor antagonist, and 5-HT1A receptor agonist 7, 8
The American College of Physicians recommends selecting between cognitive behavioral therapy or second-generation antidepressants (including vortioxetine) after discussing treatment effects, adverse effects, cost, accessibility, and patient preferences 8
The 20 mg dose achieved 39.2% response rate and 22.3% remission rate at 8 weeks, compared to 28.4% response and 14.2% remission with placebo 2