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Mechanism Of action

The mechanism of the antidepressant effect of vilazodone is not fully understood but is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone's antidepressant effect are unknown.


Vilazodone binds with high affinity to the serotonin reuptake site (Ki= 0.1 nM), but not to the norepinephrine (Ki=56 nM) or dopamine (Ki=37 nM) reuptake sites. Vilazodone potently and selectively inhibits reuptake of serotonin (IC50= 1.6 nM). Vilazodone also binds selectively with high affinity to 5-HT1A receptors (IC50=2.1 nM) and is a 5-HT1A receptor partial agonist.

Cardiac Electrophysiology

Treatment with VIIBRYD did not prolong the QTc interval. The effect of VIIBRYD [20, 40, 60, and 80 mg (2 times the recommended dosage)] on the QTc interval was evaluated in a randomized, placebo-, and active-controlled (moxifloxacin 400 mg), parallel-group, thorough QTc study in 157 healthy subjects. The study demonstrated an ability to detect small effects. The upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc interval was below 10 msec, based on the individual correction method (QTcI). Thus, at doses of 2 times the recommended dosage, VIIBRYD did not prolong the QTc interval to a clinically relevant extent.


Vilazodone activity is due primarily to the parent drug. The pharmacokinetics of vilazodone (5 mg – 80 mg) are dose-proportional. Accumulation of vilazodone after administration of single VIIBRYD doses did not vary with dose, and steady-state was achieved in about 3 days. Elimination of vilazodone is primarily by hepatic metabolism with a terminal half-life of approximately 25 hours. At steady-state, after daily dosing of VIIBRYD 40 mg under fed conditions, the mean Cmax value was 156 ng/mL, and the mean AUC (0-24 hours) value was 1645 ng·h/mL.


Vilazodone concentrations peaked at a median of 4-5 hours (Tmax) after VIIBRYD administration and declined with a terminal half-life of approximately 25 hours. The absolute bioavailability of vilazodone was 72% with food.Vilazodone AUC and Cmax in the fasted state can be decreased by approximately 50% and 60%, respectively, compared to the fed state. Administration without food can result in inadequate drug concentrations and may reduce effectiveness.

Coadministration of VIIBRYD with ethanol or with a proton pump inhibitor (pantoprazole) did not affect the rate or extent of vilazodone absorption. In addition, neither the Tmax nor terminal elimination rate of vilazodone was altered by coadministration with either pantoprazole or ethanol.

Absorption is decreased by approximately 25% if vomiting occurs within 7 hours of ingestion; no replacement dose is needed.


Vilazodone is widely distributed and approximately 96-99% protein-bound. Administration of VIIBRYD to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein. The interaction between vilazodone and other highly protein-bound drugs has not been evaluated.

Metabolism and Elimination

VIIBRYD is extensively metabolized through CYP and non-CYP pathways (possibly by carboxylesterase), with only 1% of the dose recovered in the urine and 2% of the dose recovered in the feces as unchanged vilazodone. CYP3A4 is primarily responsible for its metabolism among CYP pathways, with minor contributions from CYP2C19 and CYP2D6.

Drug Interaction Studies

Figure 1 below includes the impact of other drugs on the pharmacokinetics of vilazodone [see DRUG INTERACTIONS].

Figure 1: Effect of Other Drugs on Vilazodone Pharmacokinetics

Effect of Other Drugs on Vilazodone Pharmacokinetics - Illustration

In vitro studies indicate that vilazodone is unlikely to inhibit or induce the metabolism of substrates for CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 or 3A5, except for CYP2C8. The effect of vilazodone on CYP2C8 activity has not been tested in vivo. Figure 2 below includes the impact of vilazadone on the pharmacokinetics of other drugs in vivo.

Figure 2: Impact of Vilazodone on Other Drug Pharmacokinetics

Impact of Vilazodone on Other Drug Pharmacokinetics - Illustration

Studies in Specific Populations

The presence of mild to severe renal impairment or mild to severe hepatic impairment did not affect the apparent clearance of vilazodone (see Figure 3). There were no pharmacokinetic differences of vilazodone in geriatric patients compared to younger patients, or between males and females (see Figure 3).

Figure 3: Impact of Intrinsic Factors on Vilazodone Pharmacokinetics

Impact of Intrinsic Factors on Vilazodone Pharmacokinetics - Illustration

Clinical Studies

The efficacy of VIIBRYD as a treatment for major depressive disorder was demonstrated in four multicenter, randomized, double-blind, placebo-controlled studies in adult (18-70 years of age) outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for MDD. Three 8-week studies evaluated the efficacy of VIIBRYD 40 mg (Studies 1-3) and one 10-week study (Study 4) evaluated the efficacy of VIIBRYD 20 mg and 40 mg (see Table 5). In these studies, patients were randomized to either 20 mg or 40 mg, or placebo once daily with food. Patients were either titrated over 1week to a dose of 20 mg daily or over 2 weeks to a dose of 40 mg once daily of VIIBRYD with food. VIIBRYD was superior to placebo in the improvement of depressive symptoms as measured by the change from baseline to endpoint visit in the Montgomery-Asberg Depression Rating Scale (MADRS) total score for both doses. The MADRS is a ten-item, clinician-rated scale used to assess severity of depressive symptoms. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression. Clinical Global Improvement - Severity (CGI-S) was evaluated in Studies 3 and 4. VIIBRYD 20 mg and 40 mg demonstrated superiority over placebo as measured by improvement in CGI-S score.

Table 5: Summary of Results for the Primary Efficacy Endpoint - MADRS Total Score

Study Number Treatment Group Number of Patients a Mean Baseline Score
LS Mean Change from Baseline
Placebo-subtracted Difference b (95% CI)
Study 1 VIIBRYD 40mg/day 198 30.8
(-5.2, -1.3)
Placebo 199 30.7
Study 2 VIIBRYD 40 mg/day 231 31.9
(-4.4, -0.6)
Placebo 232 32.0
Study 3 VIIBRYD 40 mg/day 253 30.7
(-6.9, -3.3)
Placebo 252 30.9
Study 4 VIIBRYD 20 mg/day* 288 31.3
(-4.3, -0.8)
VIIBRYD 40 mg/day* 284 31.2
(-4.6, -1.1)
Placebo 281 31.4
SD = standard deviation; SE = standard error; LS Mean = least-square mean; CI = confidence interval
a based on patients who took study medication and had baseline and postbaseline MADRS assessments
b difference
(drug minus placebo) in least-square mean change from baseline to endpoint
* All VIIBRYD treatment dose groups remained statistically significant compared with placebo after adjusting for multiplicity

Baseline demographics information were generally similar across all treatment groups. Examination of population subgroups based on age (there were few patients over 65), gender and race did not reveal any clear evidence of differential responsiveness.

Last reviewed on RxList: 1/9/2016
This monograph has been modified to include the generic and brand name in many instances.

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