What is the maximum recommended dose of Viibryd (vilazodone) for an adult with major depressive disorder, and are dose adjustments required for elderly patients or those with moderate to severe hepatic impairment?

Maximum Dosing of Viibryd (Vilazodone)

The maximum recommended dose of vilazodone is 40 mg once daily taken with food, and no dose adjustment is required for elderly patients or those with hepatic impairment of any severity. 1

Standard Dosing Protocol

• Target dose: 20–40 mg orally once daily with food 1
• Titration schedule:
  • Start at 10 mg once daily with food for 7 days
  • Increase to 20 mg once daily with food
  • May increase to 40 mg once daily after a minimum of 7 additional days 1
• Absolute maximum: 40 mg per day—this is the ceiling dose and should not be exceeded 1, 2

Food requirement is critical: Vilazodone must be taken with food to ensure adequate plasma concentrations and therapeutic effect 1, 2. Without food, systemic exposure is significantly reduced, potentially compromising efficacy.

Dose Adjustments for Special Populations

Elderly Patients (≥65 years)

• No dose reduction required based on age alone 1
• Pharmacokinetic studies demonstrate similar drug exposure in elderly subjects (>65 years) compared with younger adults (24–55 years) 1
• The standard 40 mg maximum dose applies to elderly patients 1
• Caution: Elderly patients may be at greater risk for hyponatremia with serotonergic antidepressants, so monitor sodium levels 1

Hepatic Impairment

• No dose adjustment necessary for mild, moderate, or severe hepatic impairment (Child-Pugh scores 5–15) 1, 3
• Pharmacokinetic data show that vilazodone exposure (Cmax and AUC) remains similar across all degrees of hepatic dysfunction 3
• In severe hepatic impairment, mean Cmax and AUC were actually 29% and 17% lower than in healthy controls, not higher—eliminating concern for drug accumulation 3
• The standard 40 mg maximum dose is safe in hepatic impairment 1, 3

Renal Impairment

• No dose adjustment necessary for mild to severe renal impairment (GFR 15–90 mL/min) 1, 4
• Vilazodone is extensively hepatically metabolized with minimal renal excretion (<1% recovered unchanged in urine) 4
• Pharmacokinetic parameters (Cmax, AUC, half-life, clearance) are not substantially affected by renal dysfunction 4
• The standard 40 mg maximum dose applies to patients with renal impairment 4

Drug Interaction Dose Modifications

Strong CYP3A4 Inhibitors

• Reduce maximum dose to 20 mg once daily during concomitant use of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, voriconazole, ketoconazole) 1, 2
• Resume original dose when the CYP3A4 inhibitor is discontinued 1

Strong CYP3A4 Inducers

• Consider increasing dose up to 80 mg once daily (2-fold increase) over 1–2 weeks in patients taking strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) for >14 days 1
• Gradually reduce back to original dose over 1–2 weeks when the inducer is discontinued 1
• This is the only scenario where vilazodone may exceed 40 mg daily 1

Discontinuation Protocol

• Gradual taper is recommended rather than abrupt cessation to minimize discontinuation symptoms 1
• From 40 mg daily:
  • Taper to 20 mg once daily for 4 days
  • Then 10 mg once daily for 3 days
  • Then discontinue 1
• From 20 mg daily:
  • Taper to 10 mg once daily for 7 days
  • Then discontinue 1

Common Pitfalls to Avoid

• Do not exceed 40 mg daily except when using strong CYP3A4 inducers (where up to 80 mg may be considered) 1
• Do not adjust dose for age, gender, renal function, or hepatic function—the standard dosing applies across these populations 1, 4, 3
• Do not administer without food—this significantly reduces bioavailability and therapeutic effect 1, 2
• Do not increase dose more frequently than every 7 days—allow adequate time between titration steps 1
• Do not combine with MAOIs or start within 14 days of MAOI discontinuation (and vice versa) due to serotonin syndrome risk 1