The discovery and development of vilazodone for the treatment of depression: a novel antidepressant or simply another SSRI?

  title={The discovery and development of vilazodone for the treatment of depression: a novel antidepressant or simply another SSRI?},
  author={Lee A. Dawson},
  journal={Expert Opinion on Drug Discovery},
  pages={1529 - 1539}
  • L. Dawson
  • Published 21 November 2013
  • Biology, Psychology
  • Expert Opinion on Drug Discovery
Introduction: Vilazodone is the newest serotonergic antidepressant to be approved by the FDA for the treatment of major depressive disorder (MDD). Vilazodone is a combined serotonin specific reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist. It was originally designed based on the premise that negative feedback circuitry mediated through somatodendritic 5-HT1 autoreceptors, limits the acute SSRI-induced enhancements in serotonergic neurotransmission. Therefore, the combination of… 
Evaluation of vilazodone for the treatment of depressive and anxiety disorders
Vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options, and more studies are needed to establish its efficacy and long-term safety.
Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs.
Health resource use and costs of vilazodone and other selective serotonin re-uptake inhibitors in treating major depressive disorder
MDD treatment with vilazodone was associated with significantly lower rates of inpatient and emergency services, and with significant lower all-cause medical service costs and numerically (non-significantly) lower total costs to payers than with the other SSRIs included in this study.
Emerging drugs for the treatment of anxiety
This review will provide a critical summary of current pharmacological approaches to the treatment of anxiety and will examine the pharmacotherapeutic pipeline for treatments in development.
[Multimodal serotonergic antidepressants].
  • D. S. Danilov
  • Psychology
    Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
  • 2017
The data presented suggest the rationale for unifying all selective serotonergic antidepressants, simultaneously inhibiting the serotonin reuptake and directly interacting with serotonin receptors, in one group of 'multimodal serotonergy antidepressants'.
Serotonin: a never-ending story.
  • B. Olivier
  • Psychology, Biology
    European journal of pharmacology
  • 2015
Evaluating the efficacy of vilazodone in achieving remission in patients with major depressive disorder: post-hoc analyses of a phase IV trial
Treatment with vilazodone 40 mg/day may help adult patients with major depressive disorder achieve remission of depression and/or anxiety symptoms and Odds ratios and numbers needed to treat (NNTs) were calculated.
Looking back (and in)to the future: A personal reflection on ‘Serotonin autoreceptor function and antidepressant drug action’ (Hjorth et al., 2000)
  • S. Hjorth
  • Biology, Psychology
    Journal of psychopharmacology
  • 2016
The results were summarised of rat microdialysis studies carried out to examine the relative importance of 5-HT1A and 5- HT1B autoreceptors, including possible regional variation, and potential changes in autoreceptor responsiveness following chronic selective serotonin reuptake inhibitor administration.
Focus on Human Monoamine Transporter Selectivity. New Human DAT and NET Models, Experimental Validation, and SERT Affinity Exploration
A computational study on three human monoamine transporters, i.e., DAT, NET, and SERT, which highlighted the differences in binding site arrangement statistically correlated to inhibitor selectivity and confirmed 4-(benzyloxy)-4-phenylpiperidine 20a–d and 21a-d as potent SERT inhibitors.
Translocator protein mediates the anxiolytic and antidepressant effects of midazolam


Clinical utility of vilazodone for the treatment of adults with major depressive disorder and theoretical implications for future clinical use
As a new option for the treatment of major depressive disorder, vilazodone, due to its unique SPARI mechanism of action, may hold promise for patients who cannot tolerate or have not responded to previous antidepressant monotherapies.
Vilazodone: a novel antidepressant.
  • Elizabeth Choi, M. Zmarlicka, M. Ehret
  • Medicine
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2012
Its relatively high cost and adverse-effect profile, as well as a lack of data demonstrating that vilazodone can produce long-term MDD remission and offer significant advantages over the current standard of care, may limit the usefulness of vilzodone in clinical practice.
5-HT1 receptor augmentation strategies as enhanced efficacy: therapeutics for psychiatric disorders.
The rationale behind the various augmentation strategies adopted and the progress made in identifying novel therapeutics for conditions such as depression and anxiety disorders are reviewed.
Effect of chronic fluoxetine and WAY-100635 treatment on serotonergic neurotransmission in the frontal cortex
The chronic effects of fluoxetine administered in combination with the selective 5-HT1A receptor antagonist WAY-100635 and the data suggest that augmentation of an SSRI by combined pharmacotherapy with a 5- HT1A antagonist would be effective upon prolonged exposure.
Vilazodone: A 5‐HT1A Receptor Agonist/Serotonin Transporter Inhibitor for the Treatment of Affective Disorders
Preclinical in vitro evaluation has confirmed vilazodone's primary pharmacological profile both in clonal and native systems, that is, serotonin reuptake blockade and 5‐HT1A partial agonism, and in vivo and in contrast to combination of 8‐OH‐DPAT and paroxetine, vilazdone selectively enhanced serotonergic output in the prefrontal cortex of rats.
The role of serotonin receptor subtypes in treating depression: a review of animal studies
The involvement of 5- HT receptors in the antidepressant-like effects of SSRIs is complex and involves the orchestration of stimulation and blockade at different 5-HT receptor subtypes.
A review of current evidence for vilazodone in major depressive disorder
Vilazodone is a newer antidepressant possessing different action mechanisms compared to currently available antidepressants but whether it has superiority to other class of antidepressants in terms of efficacy and safety should still warrant further evaluation through more well-controlled and direct comparison clinical trials.
Behavioral studies of serotonin receptor agonists as antidepressant drugs.
  • I. Lucki
  • Biology, Psychology
    The Journal of clinical psychiatry
  • 1991
Results from clinical and preclinical studies that support the efficacy of 5-HT1A receptor agonists as antidepressants are reviewed, and it is reviewed that the antidepressant activity may be due to the activation of postsynaptic 5- HT1A receptors, although 4-HT2 receptors also activate somatodendritic autoreceptors which diminish the release of5-HT.
Behavioral studies of serotonin receptor agonists as antidepressant drugs.
Evidence is reviewed that the antidepressant activity may be due to the activation of postsynaptic 5-HT1A receptors, although 5- HT1A receptor agonists also activate somatodendritic autoreceptors which diminish the release of 4-HT, and evidence does not support the involvement of a common metabolite 1-PP in the antidepressants activity of 5-ht1Aceptor-selective azapirones.
Effectiveness of pindolol with selected antidepressant drugs in the treatment of major depression.
The results of these studies indicate that pindolol is safe when used in combination with an SSRI or moclobemide and should be tested under double-blind conditions to establish its efficacy.