What is the starting dose of vortioxetine (Brintellix) for an adult patient with Major Depressive Disorder (MDD), potentially with a history of treatment-resistant depression and previous Electroconvulsive Therapy (ECT), considering factors such as age, renal function, and liver disease?

Starting Dose of Vortioxetine

The recommended starting dose of vortioxetine is 10 mg administered orally once daily without regard to meals, with planned increase to 20 mg/day as tolerated to achieve optimal efficacy. 1

Standard Dosing Protocol

Initial dosing:

• Start at 10 mg once daily (can be taken with or without food) 1, 2
• This represents the FDA-approved starting dose for all adult patients with major depressive disorder 1

Dose escalation:

• Increase to 20 mg/day as tolerated, as this dose demonstrates superior efficacy compared to 10 mg/day 1, 3
• In flexible-dose studies, 48% of patients were increased to 20 mg/day after just 1 week, and 64.3% ultimately received 20 mg/day as their final maintenance dose 3
• The 20 mg dose shows significant separation from placebo starting at week 2, while 10 mg does not separate until week 4 3
• At 8 weeks, 20 mg/day produces significantly greater improvement in depression scores compared to 10 mg/day (difference of -1.03 MADRS points, p<0.05) 3

Lower dose option:

• Consider 5 mg/day only for patients who cannot tolerate higher doses 1
• The 5 mg dose has limited efficacy data and should not be used as a routine starting dose 4

Dose Modifications for Specific Populations

CYP2D6 poor metabolizers:

• Maximum recommended dose is 10 mg/day (do not exceed this) 1
• No adjustment needed for the starting dose of 10 mg 1

Age considerations:

• No dose adjustment needed based on age alone 2
• The same 10 mg starting dose applies to elderly patients 1

Renal impairment:

• No dose adjustment required regardless of severity 2

Hepatic impairment:

• No dose adjustment needed for mild to moderate hepatic disease 2
• Data for severe hepatic impairment are limited 1

Treatment-Resistant Depression Context

For patients with treatment-resistant depression or previous ECT history:

• Use the same standard starting dose of 10 mg/day 1
• Plan for dose escalation to 20 mg/day within 1-2 weeks if tolerated, as these patients may benefit from the higher dose more rapidly 3
• The 20 mg dose demonstrates clear dose-response superiority and should be the target dose for most patients 3

Tolerability Considerations

Adverse event profile:

• Nausea is the most common adverse event and is dose-dependent 2
• The incidence of adverse events is not significantly increased at 20 mg/day compared to 10 mg/day 3
• Most adverse events are mild to moderate in severity 5

Key clinical pitfall:

• Do not routinely start at 5 mg or maintain patients at subtherapeutic doses—vortioxetine 20 mg/day was the effective dose in US studies, and lower doses (2.5 mg and 5 mg) failed to separate from placebo in controlled trials 2, 4

Discontinuation Protocol

• Vortioxetine can be discontinued abruptly without tapering 1
• However, for doses of 15 mg/day or 20 mg/day, reduce to 10 mg/day for one week prior to full discontinuation to minimize potential withdrawal symptoms 1, 2