A Review of Vilazodone, Serotonin, and Major Depressive Disorder



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Objective: To review the mechanism of selective serotonin reuptake inhibitor (SSRI)–mediated serotonergic neurotransmission, focusing on serotonin 1A (5-HT1A) autoreceptors, which are proposed to be involved in delaying therapeutic efficacy. Vilazodone was specifically designed to function both as an SSRI and a partial agonist at 5-HT1A receptors. This combined mechanism is proposed to decrease time to efficacy, minimize sexual side effects, and provide concomitant anxiolytic properties.

Data Sources: A PubMed search of all English-language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT1A, depression and buspirone, depression and pindolol, and vilazodone.

Study Selection: We found 47 articles and abstracts that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol, buspirone, and vilazodone in depression.

Data Extraction: This review summarizes current literature involving antidepressant activity, the role of 5-HT1A autoreceptors, and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists, with a focus on vilazodone.

Results: Vilazodone has demonstrated efficacy in 2 large, randomized, double-blind, placebo-controlled trials in major depressive disorder. Results suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety. A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy.

Conclusions: If future studies corroborate the clinical benefits attributed to its mechanism of action, vilazodone may show potential advantages in terms of onset of action, sexual side effects, and anxiolytic activity in patients with major depressive disorder.

Prim Care Companion CNS Disord 2014;16(1):doi:10.4088/PCC.13r01554

Submitted: July 10, 2013; accepted October 1, 2013.

Published online: January 9, 2014.

Corresponding author: Kerri A. Pierz, PhD, c/o John Edwards, 185 Hudson St, Plaza 5 28th Floor, Jersey City, NJ 07311 (kerri.pierz@gmail.com).

Prim Care Companion CNS Disord 2014;16(1):doi:10.4088/PCC.13r01554