Vilazodone is a selective serotonin reuptake inhibitor (SSRI) and partial serotonin receptor agonist which is used in the therapy of major depressive disorders. In premarketing clinical trials, vilazodone therapy was not associated with an increased rate of elevations in serum aminotransferase levels, and it has yet to be linked to instances of clinically apparent acute liver injury.


Vilazodone (vil az' oh done) is an SSRI that acts by blocking the reuptake of serotonin in CNS synaptic clefts, thus increasing serotonin levels in the brain which is associated with its psychiatric effects. Vilazodone is also a partial serotonin (5-HT1A) receptor agonist, which may add to its antidepressant effects. Vilazodone was approved for use in the United States in 2011 for use in treatment of major depressive disorder. There is limited clinical experience with its use. Vilazodone is available as tablets of 10, 20 and 40 mg under the brand name Viibryd. The recommended initial dose of vilazodone in adults is 10 mg daily, which can then be increased to the typical maintenance dose of 40 mg once daily. Common, non-serious side effects include diarrhea, nausea, fatigue, drowsiness, headache, insomnia, weight gain and sexual dysfunction. Overdose is associated with acute serotonin syndrome. Rare, but potentially severe adverse effects include suicidal thinking and behavior, activation of symptoms of mania, serotonin syndrome, sexual dysfunction, hyponatremia and hypersensitivity reactions.


In premarketing studies, liver test abnormalities were uncommon in patients taking vilazodone (<1%) and no more frequent than in placebo recipients. No instances of acute, clinically apparent liver injury attributed to vilazodone have been reported. However, vilazodone has been in use for a short period of time. Most other SSRIs in clinical use have been associated with rare instances of acute liver injury, usually arising within 2 to 8 weeks of starting therapy. The pattern of serum enzyme elevations varied from hepatocellular to cholestatic. Autoimmune markers are not common, but immunoallergic features (rash, fever, eosinophilia) are frequent but usually not prominent. Most cases of acute liver injury due to SSRIs are mild-to-moderate in severity and resolve within one to three months. Acute liver failure due to the SSRIs has been described, but is very rare. No such cases have been linked to vilazodone use.

Likelihood score: E* (unproven but suspected rare cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which vilazodone might cause liver injury is not known. Vilazodone is metabolized in the liver at least in part through cytochrome P450 pathways, predominantly CYP 3A4. It is susceptible to significant drug-drug interactions with increased serum levels when given with strong CYP 3A4 inhibitors (such as ketoconazole) and with reduced concentrations when given with strong inducers (such as carbamazepine).

Outcome and Management

The serum aminotransferase elevations that occur on amoxapine therapy are usually self-limited and do not require dose modification or discontinuation of therapy. No instances of acute liver failure or vanishing bile duct syndrome due to amoxapine have been reported. There is no information on cross sensitivity to liver injury between amoxapine and other tricyclic antidepressants, but switching to another class of agents (such as the selective serotonin reuptake inhibitors) is probably prudent.

Drug Class: Antidepressant Agents

Other Drugs in the Subclass, SNRIs/SSRIs: Citalopram, Escitalopram, Duloxetine, Fluoxetine, Fluvoxamine, Levomilnacipran, Paroxetine, Sertraline, Venlafaxine, Vortioxetine



Vilazodone – Viibryd®


Antidepressant Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 08 April 2020

Abbreviations: MAO inhibitor, monoamine oxidase inhibitor; SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin and norepinephrine reuptake inhibitor.

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    (Among 1485 patients with major depression enrolled in two controlled trials of vilazodone, diarrhea, nausea and insomnia were the most frequent adverse events and there were no serum ALT elevations above 3 times ULN or serious hepatic adverse events).
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    (Analysis of data sources from 4 European countries identified 3.2 million persons initiating antidepressant therapy among whom there was no increased risk for acute liver injury for agomelatine compared to citalopram, an SSRI with a low rate of hepatotoxicity).
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