Limits...
Vilazodone for the treatment of major depressive disorder: focusing on its clinical studies and mechanism of action.

Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU - Psychiatry Investig (2015)

Bottom Line: In terms of its mechanism of actions, we sought to elaborate them mainly through preclinical animal studies.Vilazodone is an antidepressant with novel mechanism of action because its chemical structure is unrelated to conventional antidepressant, and it has a selective serotonin (5-HT) reuptake inhibitor and 5-HT1A receptor partial agonist profile.Vilazodone is an effective and safe treatment option with its novel action mechanisms for patients with depression.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.

ABSTRACT
We tried to review and update clinical and preclinical studies evaluating vilazodone's role as an antidepressant for patients with major depressive disorder (MDD). In terms of its mechanism of actions, we sought to elaborate them mainly through preclinical animal studies. A data search was conducted in November 1, 2013, using the key terms "vilazodone" or "Viibryd," in PubMed and Medline databases. All published and unpublished studies are included and citations from publications were also reviewed for additional references. Five unpublished, phase-II and two pivotal published phase-III clinical trials with nearly identical design (8-week, double-blind, randomized, and placebo-controlled) investigated efficacy of vilazodone, were found for the treatment of patients with MDD. Two post-hoc studies and one long-term open study were also included. Data were thoroughly reviewed to incorporate the pharmacology, action mechanism, efficacy and safety for the vilazodone in the treatment of major depressive disorder. Vilazodone is an antidepressant with novel mechanism of action because its chemical structure is unrelated to conventional antidepressant, and it has a selective serotonin (5-HT) reuptake inhibitor and 5-HT1A receptor partial agonist profile. Vilazodone is an effective and safe treatment option with its novel action mechanisms for patients with depression. Its putative benefits compared with other antidepressants must be thoroughly studied in adequately-powered and well-designed future clinical trials.

No MeSH data available.


Related in: MedlinePlus

Opposite role of pre- and post-synpatic 5HT1A receptors in depression. 1) Activation of pre-synaptic 5HT1A receptors, autoreceptors, decrease the firing and secretion of 5-HT, where as 2) activation of post-synaptic 5HT1A receptors increase firing and secretion of 5HT, 3) Acute SSRI administration results in net increase of extracellular 5HT, 4) which is immediately counteracted by neuronal negative feedback mechanisms mediated by 5-HT1A auto-receptors causing therapeutic lag of SSRI. 5HT: serotonin, SERT: serotonin transporter.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4390584&req=5

Figure 1: Opposite role of pre- and post-synpatic 5HT1A receptors in depression. 1) Activation of pre-synaptic 5HT1A receptors, autoreceptors, decrease the firing and secretion of 5-HT, where as 2) activation of post-synaptic 5HT1A receptors increase firing and secretion of 5HT, 3) Acute SSRI administration results in net increase of extracellular 5HT, 4) which is immediately counteracted by neuronal negative feedback mechanisms mediated by 5-HT1A auto-receptors causing therapeutic lag of SSRI. 5HT: serotonin, SERT: serotonin transporter.

Mentions: Cumulative evidence suggests that pre- and postsynaptic 5HT1A receptors have opposite role in depression.23 Pre-synaptic 5HT1A receptors located on raphe nuclei are autoreceptors, so activating these pre-synaptic 5HT1A receptors could decreases the firing and secretion of 5-HT.24,25 In contrast, post-synaptic receptors located on the hippocampus may activate firing and secretion of 5-HT.26 When an antidepressant (i.e., SSRI) is administered acutely, it results in increase of extra-neuronal 5-HT level. However, this increase of 5-HT is immediately counteracted by neuronal negative feedback mechanisms mediated by 5-HT1A autoreceptors (Figure 1).27 Chronic stimulation of 5HT1A receptors (via continuous antidepressant) may result in desensitization of pre-synaptic autoreceptor but not the postsynaptic receptors.28,29 Efficacy of the autoreceptor-mediated negative feedback will be reduced, enabling a normalization of 5-HT release and a greater activation of post-synaptic 5-HT receptors result in improvement of depression symptoms.23 Thus, negative feedback mechanism described above is speculated to play major role in the delayed action of antidepressants because it takes time to overcome the autoreceptor-mediated serotonin inhibition and 5-HT1A autoreceptor down-regulation with SSRI.30 Desensitization of the autoreceptors before increasing extracellular serotonin concentration is thought to be important in determining the fast onset of antidepressants. 31,32


Vilazodone for the treatment of major depressive disorder: focusing on its clinical studies and mechanism of action.

Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU - Psychiatry Investig (2015)

Opposite role of pre- and post-synpatic 5HT1A receptors in depression. 1) Activation of pre-synaptic 5HT1A receptors, autoreceptors, decrease the firing and secretion of 5-HT, where as 2) activation of post-synaptic 5HT1A receptors increase firing and secretion of 5HT, 3) Acute SSRI administration results in net increase of extracellular 5HT, 4) which is immediately counteracted by neuronal negative feedback mechanisms mediated by 5-HT1A auto-receptors causing therapeutic lag of SSRI. 5HT: serotonin, SERT: serotonin transporter.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390584&req=5

Figure 1: Opposite role of pre- and post-synpatic 5HT1A receptors in depression. 1) Activation of pre-synaptic 5HT1A receptors, autoreceptors, decrease the firing and secretion of 5-HT, where as 2) activation of post-synaptic 5HT1A receptors increase firing and secretion of 5HT, 3) Acute SSRI administration results in net increase of extracellular 5HT, 4) which is immediately counteracted by neuronal negative feedback mechanisms mediated by 5-HT1A auto-receptors causing therapeutic lag of SSRI. 5HT: serotonin, SERT: serotonin transporter.
Mentions: Cumulative evidence suggests that pre- and postsynaptic 5HT1A receptors have opposite role in depression.23 Pre-synaptic 5HT1A receptors located on raphe nuclei are autoreceptors, so activating these pre-synaptic 5HT1A receptors could decreases the firing and secretion of 5-HT.24,25 In contrast, post-synaptic receptors located on the hippocampus may activate firing and secretion of 5-HT.26 When an antidepressant (i.e., SSRI) is administered acutely, it results in increase of extra-neuronal 5-HT level. However, this increase of 5-HT is immediately counteracted by neuronal negative feedback mechanisms mediated by 5-HT1A autoreceptors (Figure 1).27 Chronic stimulation of 5HT1A receptors (via continuous antidepressant) may result in desensitization of pre-synaptic autoreceptor but not the postsynaptic receptors.28,29 Efficacy of the autoreceptor-mediated negative feedback will be reduced, enabling a normalization of 5-HT release and a greater activation of post-synaptic 5-HT receptors result in improvement of depression symptoms.23 Thus, negative feedback mechanism described above is speculated to play major role in the delayed action of antidepressants because it takes time to overcome the autoreceptor-mediated serotonin inhibition and 5-HT1A autoreceptor down-regulation with SSRI.30 Desensitization of the autoreceptors before increasing extracellular serotonin concentration is thought to be important in determining the fast onset of antidepressants. 31,32

Bottom Line: In terms of its mechanism of actions, we sought to elaborate them mainly through preclinical animal studies.Vilazodone is an antidepressant with novel mechanism of action because its chemical structure is unrelated to conventional antidepressant, and it has a selective serotonin (5-HT) reuptake inhibitor and 5-HT1A receptor partial agonist profile.Vilazodone is an effective and safe treatment option with its novel action mechanisms for patients with depression.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.

ABSTRACT
We tried to review and update clinical and preclinical studies evaluating vilazodone's role as an antidepressant for patients with major depressive disorder (MDD). In terms of its mechanism of actions, we sought to elaborate them mainly through preclinical animal studies. A data search was conducted in November 1, 2013, using the key terms "vilazodone" or "Viibryd," in PubMed and Medline databases. All published and unpublished studies are included and citations from publications were also reviewed for additional references. Five unpublished, phase-II and two pivotal published phase-III clinical trials with nearly identical design (8-week, double-blind, randomized, and placebo-controlled) investigated efficacy of vilazodone, were found for the treatment of patients with MDD. Two post-hoc studies and one long-term open study were also included. Data were thoroughly reviewed to incorporate the pharmacology, action mechanism, efficacy and safety for the vilazodone in the treatment of major depressive disorder. Vilazodone is an antidepressant with novel mechanism of action because its chemical structure is unrelated to conventional antidepressant, and it has a selective serotonin (5-HT) reuptake inhibitor and 5-HT1A receptor partial agonist profile. Vilazodone is an effective and safe treatment option with its novel action mechanisms for patients with depression. Its putative benefits compared with other antidepressants must be thoroughly studied in adequately-powered and well-designed future clinical trials.

No MeSH data available.


Related in: MedlinePlus