Vilazodone: A Novel Antidepressant

Vilazodone was approved by the Food and Drug Administration in the U.S. earlier this year, but is just now becoming available in pharmacies for prescription use.  The drug is marketed in the U.S. under the trade name Viibyd.  It is novel in that it the only antidepressant that combines two mechanisms that can increase serotonin in the brain cortex: selective serotonin reuptake inhibition and partial agonism of the 5HT1A receptor.  There are multiple selective serotonin reuptake inhibitors, i.e. fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro).  

There are also compounds that have an agonistic effect on the 5HT1A receptor.  These include:
Antidepressants: trazodone, nefazodone
Antianxiety drugs: buspirone
Atypical antipsyhotics: aripiprazole, ziprasidone, clozapine, asenapine
Illicit drugs/compounds: MDMA (ecstasy), LSD, psylocybin, cannabidiol (cannabis)
Antimigraine compounds: ergotamine
Other compounds: yohimbine

The combination of SSRI and 5HT1A agonist effect may synergistically increase serotonergic transmission.  

Two published clinical trials on vilazodone are available on PubMed.  The table below summarizes some of the key findings from the two published trials.

The dose of vilazodone studied was 40 mg in both studies.  Because of the common occurrence of gastrointestinal side effects, doses are typically initiated at a smaller level and increased to 40 mg over the first week or so.  The pattern and prevalence of gastrointestinal side effects with vilazodone appears similar to levels seen in previous SSRI trials.  Although headache was commonly reported with vilazodone, the rate did not differ from the rate endorsed by placebo.  Dizziness, dry mouth, insomnia and abnormal dreaming were endorsed at a higher level with vilazodone but by less than 10% of the subjects.

Although vilazodone was statistically superior to placebo on almost all depression measures, it was not statistically superior in remission rates in the Kahn study.  This finding along with the relatively low absolute response rate of 27.3% in the vilazodone group is a little disappointing.

The response and remission rates found in these two studies were similar to SSRIs.  Head to head comparison with an SSRI would be informative to see if vilazdone has any effectiveness or adverse event superiority.  Sexual side effects are common with the SSRIs and the two randomized vilazodone studies reported no difference in sexual side effects between vilazodone and placebo.  Additionally, the Rickels study showed some evidence for anxiety symptom reduction.  Clinical trials examining the effectiveness of vilazodone for anxiety disorders will likely be soon completed.

Disclosure:  The author has no stock in the parent company of vilazodone (Forest Labs).  Additionally no honoraria or research grant support has been received related to this drug.  The author received no reimbursement for writing this post and the comments are entirely those of the author.

Information on the agonists for the 5HT1A receptor obtained from Wikipedia.

Chemical molecular structure of vilazodone from Creative Commons file at Wikepedia by author Meodipt.

Rickels K, Athanasiou M, Robinson DS, Gibertini M, Whalen H, & Reed CR (2009). Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. The Journal of clinical psychiatry, 70 (3), 326-33 PMID: 19284933


Khan A, Cutler AJ, Kajdasz DK, Gallipoli S, Athanasiou M, Robinson DS, Whalen H, & Reed CR (2011). A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. The Journal of clinical psychiatry, 72 (4), 441-7 PMID: 21527122