What is the recommended treatment regimen for a patient with moderate depression and anxiety using Vortioxetine (Brintellix)?

Vortioxetine Treatment Regimen for Moderate Depression and Anxiety

For a patient with moderate depression and anxiety, start vortioxetine at 10 mg once daily, then increase to 20 mg daily as tolerated, with the option to reduce to 5 mg daily if higher doses are not tolerated. 1

Dosing Algorithm

Initial Dosing

• Start with 10 mg once daily without regard to meals 1
• This represents the FDA-approved starting dose for major depressive disorder 1
• No "test dose" is required, unlike some SSRIs where subtherapeutic dosing may be advisable due to initial anxiety/agitation 2

Dose Titration

• Increase to 20 mg daily as tolerated 1
• The 20 mg dose was specifically shown to be effective in US studies for major depressive disorder 3
• For patients with comorbid depression and anxiety, forced up-titration to 20 mg after 1 week was well tolerated and demonstrated significant improvements in both depressive and anxiety symptoms 4
• Consider 5 mg daily only for patients who do not tolerate higher doses 1

Timeline for Dose Adjustment

• Vortioxetine has a mean terminal half-life of approximately 66 hours, with steady-state achieved within 2 weeks 5
• In clinical studies with comorbid depression and anxiety, up-titration to 20 mg occurred after 1 week and was well tolerated 4
• This contrasts with shorter half-life SSRIs (sertraline, citalopram) which require 1-2 week titration intervals, or longer half-life SSRIs (fluoxetine) requiring 3-4 week intervals 2

Monitoring and Assessment

Response Assessment Timeline

• Assess treatment response at 4 and 8 weeks using standardized validated instruments 2
• Monitor for symptom relief, side effects, adverse events, and patient satisfaction 2
• In clinical trials, clinically meaningful improvements were observed after 8 weeks of treatment 4

Treatment Adjustment at 8 Weeks

• If little improvement despite good adherence after 8 weeks, adjust the regimen 2
• Options include: adding psychological intervention, changing medication, or switching from group to individual therapy 2
• For patients with both depression and anxiety, prioritize treatment of depressive symptoms, or consider a unified CBT protocol addressing both 2

Special Dosing Considerations

CYP2D6 Poor Metabolizers

• Maximum recommended dose is 10 mg daily in known CYP2D6 poor metabolizers 1
• Vortioxetine is metabolized by cytochrome P450 enzymes, with CYP2D6 playing a significant role 5

Drug Interactions Requiring Dose Adjustment

• Reduce vortioxetine dose by half when coadministered with strong CYP2D6 inhibitors (e.g., bupropion) 1, 5
• Consider dose increase (up to 3 times original dose maximum) when coadministered with strong CYP inducers (e.g., rifampin) for more than 14 days 1, 5

No Adjustment Needed

• No dose adjustment required based on age, sex, race, body size, or renal/mild-to-moderate hepatic impairment 5, 3

Discontinuation Strategy

• Vortioxetine can be discontinued abruptly 1
• However, for doses of 15 or 20 mg daily, reduce to 10 mg daily for one week prior to full discontinuation to avoid potential withdrawal symptoms 1, 3
• This is more favorable than shorter-acting SSRIs (paroxetine, fluvoxamine, sertraline) which have higher risk of discontinuation syndrome 2

Safety Monitoring

Critical Warnings

• Monitor closely for suicidal thoughts and behaviors, especially in patients under 25 years old, during initial months of therapy and at dosage changes 1
• Monitor for serotonin syndrome, particularly if combining with other serotonergic agents 1
• Assess bleeding risk, especially with concomitant use of NSAIDs, aspirin, anticoagulants, or antiplatelet drugs 1

Common Adverse Effects

• Nausea is the most common adverse event and is dose-dependent 3, 6
• Other common adverse effects (≥5% and twice placebo rate) include constipation and vomiting 1
• In long-term studies, nausea and headache were most common (≥10%), but treatment was generally well tolerated 6

Efficacy in Comorbid Depression and Anxiety

• Vortioxetine demonstrates effectiveness in reducing both depression and anxiety symptoms in patients with severe MDD comorbid with severe GAD 4
• At 8 weeks with 20 mg dosing: 61% achieved depression response, 55% achieved anxiety response, and 52% achieved response on both measures 4
• All doses (5,10, and 20 mg) were effective for relapse prevention in patients achieving remission, with relapse rates of 17-19% versus 32.5% for placebo over 28 weeks 7