Vilazodone hydrochloride, a combined SSRI and 5-HT1A receptor agonist for major depressive disorder

Vilazodone (VIIBRYD, Trovis Pharmaceuticals; New Haven, Connecticut, also known as 659746, EMD68843, SB-659746-A) is a newly introduced antidepressant that has taken approximately a decade from its discovery to approval by the Food and Drug Administration. This paper will review the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug-drug interaction potential, dosing, and administration of this agent.

Medline/PubMed/IPA/EMBASE databases were searched using the terms "vilazodone," "659746," "EMD68843," and "SB-659746-A." All English-language papers from 1985 to April 2012 were reviewed for relevance. Bibliographies of all papers were reviewed to identify further papers.

All English-language papers from 1985 to present appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any papers not identified in the searches. Data are expressed as mean or mean ± standard deviation, unless otherwise noted.

Vilazodone is the first combined selective serotonin reuptake inhibitor (SSRI)/5-HT1A receptor agonist antidepressant. Vilazodone must be administered with food to optimize bioavailability. The primary route of elimination is metabolism followed by excretion of metabolites. Advancing age and renal and hepatic impairment do not alter its disposition. Early phase II clinical trials were unable to demonstrate antidepressant efficacy. However, later phase III trials using 40 mg daily doses were able to demonstrate superior efficacy compared with placebo treatment. Adverse events, warnings, and precautions mirror those of other SSRIs.

Although there are theoretical reasons why 5-HT1A agonism may be a desirable additional property in antidepressants, there is no evidence to date that vilazodone has any advantage over existing post-tricyclic antidepressants. It has a narrow therapeutic dosing range whose upper boundary is close to that producing intolerable gastrointestinal and central nervous system adverse events. Further research will clarify and refine the role of vilazodone in the management of psychiatric disorders.