Vilazodone: a brief pharmacological and clinical review of the novel serotonin partial agonist and reuptake inhibitor

Abstract

Abstract:Background: Vilazodone is the latest US Food and Drug Administration approved antidepressant agent available in the USA. Its putative mechanism of antidepressant action enhances the release of serotonin across the brain's serotonergic pathways specifically by inhibiting the serotonin transporter, similar to a selective serotonin reuptake inhibitor (SSRI), and simultaneously stimulating serotonin-1a receptors via partial agonism, similar to the anxiolytic buspirone. This combined activity in the single vilazodone agent has been termed by the authors as being a serotonin partial agonist and reuptake inhibitor or (SPARI). Methods: A MEDLINE and Internet search was conducted and the resultant preclinical and clinical evidence was reviewed. The authors attempt to review laboratory data, animal model data and human trial data to develop a translational theory on the mechanism of antidepressant action of this agent and also its adverse effect potential. Results: Randomized, controlled empirical data for vilazodone have gained it approval for treating major depressive disorder. It combines two well known pharmacodynamic mechanisms of serotonergic action into a novel agent. Although no head-to-head studies against other antidepressants have been published, the efficacy data for vilazodone appear comparable to other known antidepressants, with similar gastrointestinal side effects to SSRI or serotonin norepinephrine reuptake inhibitor (SNRI) antidepressants, but possibly with a lower incidence of sexual side effects and weight gain. Discussion: Vilazodone will lend itself to the current armamentarium in the treatment of major depressive disorder and may hold promise for patients who cannot tolerate other antidepressants. Its unique SPARI mechanism of action could also be efficacious for patients who do not respond to SSRI or SNRI antidepressant monotherapies.

The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management

“…Vilazodone appears to have a low incidence of spontaneously reported adverse effects on sexual function, which may be related to partial agonist effects at the 5-HT1A receptor: it does not differ from placebo in improvement of sexual function during acute treatment of major depressive episodes, and the "number needed to harm" for sexual adverse effects has been estimated as 7 in men and 23 in women [79][80][81] . Treatment with the novel "multimodal" antidepressant vortioxetine is associated with a low incidence of reported adverse effects on sexual function in men (3-5%) and women (1-2%), which may relate to its antagonist effects at the 5-HT3 receptor, and to indirect effects in increasing the availability of dopamine and noradrenaline 82 .…”

Vilazodone for the Treatment of Paternal Post Natal Depression

“…SPARI actions could hypothetically lead to more antidepressant efficacy than selective SERT inhibition, and lesser sexual dysfunction due to lesser degrees of SERT inhibition than SSRIs. However these advantages have only been demonstrated in placebo controlled trials, but not in head-to-head trials of vilazodone against the SSRIs or the SNRIs [23][24][25][26][27]. Thus, there are many theoretical advantages to the SPARI combined mechanism, but proof of that advantage over current antidepressants or well-known combinations of two agents to achieve the same pharmacologic actions is still awaiting more clinical trials.…”

“…Without treatment PPND could lead to dire consequences including, deterioration in paternal mental health, loss of paternal bonding with the newborn child, which has been associated with long term later child psychiatric complications such as conduct disorders, hyperactivity, anxiety, depression, posttraumatic stress disorder and delays in language Vilazodone (Viibryd) is an oral antidepressant that is unrelated to tricyclic or tetracyclic antidepressants which was approved for the treatment of adults MDD in January 2011 [23]. It is the first-of-class of antidepressants which is classified as a serotonin partial agonist reuptake inhibitor (SPARI).…”

Developments in Psychopharmacology for Major Depressive Disorder

“…Whether this additional action of 5HT1A partial agonism boosts the efficacy of serotonin inhibition or mitigates the side effects of 5HT1A partial agonism remains unknown, but this combination of mechanisms may result in lower rates of sexual dysfunction and weight gain. (4) Another multimodal serotonergic medication in development is vortioxetine, a 5HT3a receptor antagonist, 5HT7 receptor antagonist, 5HT1B partial agonist, 5HT1A agonist, and 5HT transporter inhibitor (6). Vortioxetine has been found to reduce symptoms of depression in several Phase III trials (7-9) and has been associated with a more favorable cognitive effect profile (9); it has also been found to be effective in preventing relapse of depression in an open-label trial (10).…”

“…This medication both inhibits the serotonin transporter and acts as a partial agonist at 5HT1A receptors; thus, it is sometimes also called a SPARI (serotonin partial agonist reuptake inhibitor) (4,5). Whether this additional action of 5HT1A partial agonism boosts the efficacy of serotonin inhibition or mitigates the side effects of 5HT1A partial agonism remains unknown, but this combination of mechanisms may result in lower rates of sexual dysfunction and weight gain.…”