Efficacy and Safety of Vilazodone in Patients With Generalized Anxiety Disorder

Abstract

Objective: To evaluate the efficacy, safety, and tolerability of vilazodone as an acute treatment for generalized anxiety disorder (GAD). Vilazodone is a selective serotonin reuptake inhibitor and 5-HT 1A receptor partial agonist approved for the treatment of major depressive disorder in adults. Methods: This was a randomized, placebo-controlled, parallel-group, multicenter, flexible-dose study conducted from May 2013-March 2014. Adult patients (18-70 years, inclusive) who met DSM-IV-TR criteria for GAD were randomized (1:1) to placebo or vilazodone 20-40 mg/d for 8 weeks of double-blind treatment. Primary and secondary efficacy parameters were change from baseline to week 8 in the Hamilton Anxiety Rating Scale (HARS) total score and in the Sheehan Disability Scale (SDS) total score, respectively, analyzed using a mixed-effects model for repeated measures approach on a modified intent-to-treat population. Safety outcomes were summarized descriptively. Results: Efficacy analyses were based on 400 patients (placebo = 200, vilazodone = 200); 76% completed the study (placebo = 81%, vilazodone = 71%). The least squares mean difference (95% CI) in total score change from baseline to week 8 was statistically significant for vilazodone versus placebo on the HARS (−2.20 [−3.72 to −0.68]; P = .0048) and on the SDS (−1.89 [−3.52 to −0.26]; P = .0236). Treatment-emergent adverse events reported in ≥ 5% of vilazodone patients and at least twice the rate of placebo were nausea, diarrhea, dizziness, fatigue, delayed ejaculation, and erectile dysfunction. Conclusion: Statistically significant differences in favor of vilazodone 20-40 mg/d versus placebo were seen on all measures of anxiety and functional impairment in patients with GAD. Vilazodone was generally well tolerated, and no new safety concerns were noted. A lthough worrying is a ubiquitous human experience, the worries that characterize generalized anxiety disorder (GAD) are so pervasive and excessive that they distort cognition and create a considerable burden of illness. The physical symptoms, psychiatric symptoms, and functional impairment associated with GAD collectively generate significant individual, societal, and economic costs.1 As such, GAD is an important mental health issue that affects patients, families, health care providers, payers, employers, and society at large. 1,2 Vilazodone is a selective serotonin reuptake inhibitor (SSRI) and 5-HT 1A receptor partial agonist that is approved by the US Food and Drug Administration (FDA) for treating major depressive disorder (MDD) in adults. SSRIs are first-line agents approved for treating GAD 3 ; unlike other SSRIs, vilazodone also is a 5-HT 1A receptor partial agonist. Based on clinical-trial evidence in MDD, 4-7 the recommended daily dose of vilazodone is 20-40 mg.8 Since SSRI antidepressants used for the treatment of GAD have efficacy at the same dose levels that are effective in treating MDD, 9 vilazodone 20-40 mg/d is being evaluated for GAD treatment.A potential anxiolytic effect for vilazodone wa...

Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder

“…Five studies were carried out in adults with MDD, including four short-term (8 or 10 weeks), randomized, double-blind, placebo-controlled trials ( Rickels et al , 2009 ; Khan et al , 2011 ; Croft et al , 2014 ; Mathews et al , 2015 ) and one long-term (52 weeks), open-label study ( Robinson et al , 2011 ). Three 8-week, randomized, double-blind, placebo-controlled studies were carried out in adults with GAD ( Gommoll et al , 2015a , 2015b ; Durgam et al , 2016 ). All studies were carried out in accordance with good clinical practice guidelines (FDA guidelines, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, and/or Declaration of Helsinki) and with the approval of the institutional review board for each study site.…”

“…Key eligibility criteria for the MDD studies included the following: Diagnostic and Statistical Manual of Mental Disorders , 4th ed., text revision (DSM-IV-TR) criteria for MDD ( APA, 2000 ); current major depressive episode with a duration of at least 4 weeks to up to 2 years ( Rickels et al , 2009 ; Khan et al , 2011 ) or at least 8 weeks to up to 12 months ( Croft et al , 2014 ; Mathews et al , 2015 ); 17-item Hamilton Depression Rating Scale (HAMD 17 ) total score≥22 and item 1 (depressed mood) score≥2 ( Rickels et al , 2009 ; Khan et al , 2011 ); HAMD 17 total score≥18 ( Robinson et al , 2011 ); and Montgomery-Åsberg Depression Rating Scale total score≥26 ( Croft et al , 2014 ; Mathews et al , 2015 ). Key eligibility criteria for all of the GAD studies ( Gommoll et al , 2015a , 2015b ; Durgam et al , 2016 ) included the following: DSM-IV-TR criteria for GAD; Hamilton Anxiety Rating Scale total score≥20, item 1 (anxious mood) score≥2, and item 2 (tension) score≥2; Clinical Global Impressions-Severity of Illness score≥4; and HAMD 17 total score≤17.…”

“…In addition to MDD trials ( Rickels et al , 2009 ; Khan et al , 2011 ; Croft et al , 2014 ; Mathews et al , 2015 ), vilazodone has been investigated in adults with GAD ( Gommoll et al , 2015a , 2015b ; Durgam et al , 2016 ). Including both datasets in this post-hoc analysis provides an opportunity to evaluate the effects of vilazodone on suicidal ideation and behavior in two different patient populations, including subsets of younger adults (18–24 years).…”

Association of 5-HT1A Receptors with Affective Disorders

“…In recent years, administration of vilazodone has shown antidepressant [75,76] and anxiolytic effects by eliminating physical and somatic symptoms in women with generalized anxiety disorder, after 8 weeks of treatment at daily doses of 20-40 mg [77,78]. This effect is due to the action mechanism of this SSRI, which is a partial agonist of postsynaptic 5-HT 1A receptors.…”

The role of new antidepressants in clinical practice in Canada: a brief review of vortioxetine, levomilnacipran ER, and vilazodone

“… 40 – 43 In a post hoc pooled analysis of data from 2 clinical trials, statistically significant differences in favor of vilazodone versus placebo were seen in changes from baseline on rating scales measuring depression, global illness severity, and anxiety; significant improvement was also seen for vilazodone versus placebo on each individual item of the MADRS, suggesting efficacy across a spectrum of depressive symptoms. 44 Additional post hoc analyses of MDD clinical trial data, 45 along with results from clinical studies in patients with generalized anxiety disorder, 46 – 48 suggest that vilazodone may be particularly well suited for patients suffering from depression and having high levels of anxiety.…”