The effect of vilazodone on sexual function during the treatment of major depressive disorder.

INTRODUCTION: Sexual dysfunction is common in major depressive disorder (MDD), and many serotonergic antidepressants adversely affect sexual function. Vilazodone, a novel serotonin (5-HT) reuptake inhibitor and 5-HT1A partial agonist approved for MDD, exerts its effects at the 5-HT transporter and at both presynaptic and postsynaptic 5-HT1A receptors. This mechanism may limit sexual dysfunction. AIM: To summarize effects of vilazodone (40 mg/day, with food) on sexual function in adults with MDD. METHODS: Data sources were three Phase III studies: two 8-week, placebo-controlled studies (NCT00285376 and NCT00683592) and a 52-week open-label study (NCT00644358). Sexual function was assessed by analyzing changes from baseline to end of treatment (EOT) using validated measures. MAIN OUTCOME MEASURE: Arizona Sexual Experience Scale or Changes in Sexual Functioning Questionnaire. RESULTS: Population included 869 patients (vilazodone, 436; placebo, 433) from placebo-controlled studies and 599 patients from the open-label study. Sexual dysfunction prevalence was high (50%, men; 68%, women) before treatment and declined during treatment in vilazodone and placebo groups, indicating improvement on average. At EOT, stable/improved sexual function was observed in ≥91% of patients in placebo-controlled studies; treatment group differences in sexual dysfunction at EOT were not statistically significant for either sex. Differences vs. placebo in changes from baseline of sexual function scores were small and were generally not statistically significant; effect sizes (Cohen's D) were generally of low magnitude. In the placebo-controlled studies, 8.0% of vilazodone-treated patients and 0.9% of placebo-treated patients reported ≥1 sexual-function-related treatment-emergent adverse event (P<0.001). CONCLUSION: Half of men and two thirds of women with MDD had sexual dysfunction at baseline; sexual function improved on average in both vilazodone and placebo groups. Results suggest that vilazodone may have a small adverse impact on sexual function in adults with MDD relative to the high prevalence of sexual dysfunction at baseline.

Vilazodone lacks proarrhythmogenic potential in healthy participants: a thorough ECG study.

OBJECTIVE: Vilazodone is a potent serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD) in adults. The effect of clinical and supratherapeutic doses of vilazodone on cardiac repolarization was determined in healthy volunteers. METHODS: In this Phase 1, randomized, doubleblind, placebo- and active-controlled, 3-arm, parallel, single-center study, healthy subjects received placebo; moxifloxacin 400 mg; or vilazodone (sequentially escalated every 3 days) 10, 20, 40, 60, and 80 mg/day. The primary endpoint was the time-matched change from baseline in the QT interval corrected for heart rate (QTc) using an individual correction method (QTcI). RESULTS: Placebo-corrected time-matched analysis of the QTcI duration for the vilazodone treatment effect indicated that no vilazodone dose had an upper bound that approached or exceeded 10 ms, demonstrating no signal for a significant vilazodone effect on cardiac repolarization. Vilazodone had no significant effect on heart rate, PR, or QRS interval duration. The pharmacokinetic/pharmacodynamic model showed that the QTcI slope for vilazodone was not different from 0.0 and that the predicted increase from baseline in the QTc at Cmax for the highest therapeutic dose (156 ng/ml after 40 mg/day) was < 1 ms. The incidence of adverse events (AEs) was higher in the vilazodone group (57.6%) than in the moxifloxacin (37.0%) and placebo (35.6%) groups, though AEs were generally mild to moderate in severity and resulted in few discontinuations. CONCLUSIONS: Vilazodone had no significant effect on cardiac repolarization, heart rate, PR or QRS interval duration, or ECG morphology in healthy adult participants.

A 1-year, open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder.

Vilazodone, a selective serotonin (5-HT) reuptake inhibitor and 5-HT(1A) receptor partial agonist, was efficacious in two 8-week placebo-controlled studies in adults with major depressive disorder. This open-label, multicenter study assessed the long-term safety of vilazodone. Adult patients with a 17-item Hamilton Rating Scale for Depression score of 18 or greater received vilazodone according to a fixed-titration schedule to reach a dose of 40 mg/d continued up to 1 year. Safety assessments included adverse events (AEs), physical examinations, clinical chemistry, electrocardiograms, and the Changes in Sexual Functioning Questionnaire. Effectiveness was assessed with the Montgomery-Åsberg Depression Rating Scale and Clinical Global Impressions scales. The safety population comprised 599 patients; 254 patients completed 1 year of treatment. The most frequent AEs were diarrhea (35.7%), nausea (31.6%), and headache (20.0%); greater than 90% of these AEs were mild or moderate. Adverse events resulting in discontinuation in more than 1% of patients were nausea (1.3%) and diarrhea (1.2%). There were no clinically important changes in physical examinations, electrocardiograms, or clinical chemistries. Mean weight increased by 1.7 kg (observed cases). Changes in Sexual Functioning Questionnaire mean scores (observed cases) improved throughout treatment for both males and females. Montgomery-Åsberg Depression Rating Scale mean scores were 29.9 at baseline, 11.4 at week 8, and 7.1 at week 52 (observed cases). Vilazodone 40 mg/d for 1 year was safe and well tolerated by adults with major depressive disorder.

The efficacy profile of vilazodone, a novel antidepressant for the treatment of major depressive disorder.

OBJECTIVE: Vilazodone is a novel serotonin reuptake inhibitor and serotonin 1A receptor partial agonist approved for the treatment of major depressive disorder (MDD). This evaluation presents side-by-side efficacy data from two randomized, double-blind, placebo-controlled, short-term 8-week trials (referred to as randomized controlled trial [RCT]-1 [N = 410] and RCT-2 [N = 481]); efficacy data for demographic and clinical subgroups (derived from pooled RCT data); and effectiveness data from a 52-week, open-label, long-term study (N = 616). The objective is to summarize the efficacy profile of vilazodone at its approved dose of 40 mg/day. METHODS: The main assessment in individual pivotal trials and pooled subgroup analyses was the change from baseline to end of treatment (EOT, 8 weeks) in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Mixed-effects repeated-measures analyses were conducted in the placebo-controlled trials. Effectiveness analyses in the long-term study included mean MADRS score change over time. RESULTS: Vilazodone-treated patients in both short-term studies showed greater improvement from baseline to EOT in mean MADRS scores than placebo-treated patients (least-squares mean [LSM] treatment difference: -3.2 [p = 0.001], RCT-1; -2.5 [p = 0.009], RCT-2). Clinical Global Impressions-Improvement mean scores at EOT reflected greater improvement with vilazodone compared with placebo in both studies (LSM treatment difference: -0.4 [p = 0.001], RCT-1; -0.3 [p = 0.004], RCT-2). MADRS response rates were significantly greater among patients receiving vilazodone versus those receiving placebo (RCT-1: 40.4% versus 28.1%, respectively [p = 0.007]; RCT-2: 43.7% versus 30.3%, respectively [p = 0.002]). The greater efficacy of vilazodone versus placebo was consistent for the majority of demographic and MDD characteristic subgroups. In the long-term study, the mean MADRS score improved from 29.9 (baseline) to 11.4 (week 8), 8.2 (week 24), and 7.1 (week 52). CONCLUSION: Vilazodone 40 mg/day resulted in clinically meaningful, statistically significant improvement in MDD symptoms in two placebo-controlled, 8-week studies. Findings are supported by subgroup analysis and open-label, long-term effectiveness data. TRIAL REGISTRATION: Randomized controlled trial 1: ClinicalTrials.gov identifier: NCT00285376, http://ClinicalTrials.gov/ct2/show/NCT00285376 ; randomized controlled trial 2: ClinicalTrials.gov identifier: NCT00683592, http://ClinicalTrials.gov/ct2/show/NCT00683592 ; open-label, long-term study: ClinicalTrials.gov identifier: NCT00644358, http://ClinicalTrials.gov/ct2/show/NCT00644358 .

A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder.

OBJECTIVE: To evaluate the efficacy, and further establish the safety profile, of oral once-daily vilazodone, a potent and selective serotonin 1A receptor partial agonist and reuptake inhibitor, in the treatment of major depressive disorder (MDD). METHOD: This phase 3, randomized, double-blind, placebo-controlled, 8-week study (conducted March 2008-February 2009) enrolled 481 adults with DSM-IV-TR-defined MDD. Patients received vilazodone (titrated to 40 mg/d) or placebo. The primary efficacy endpoint was change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to end of treatment. Secondary efficacy measures included MADRS and 17-item Hamilton Depression Rating Scale (HDRS-17) response and change in HDRS-17, HDRS-21, Hamilton Anxiety Rating Scale (HARS), Clinical Global Impressions-Severity of Illness (CGI-S), and Clinical Global Impressions-Improvement (CGI-I) scores. The Changes in Sexual Functioning Questionnaire (CSFQ) was administered at baseline and week 8. RESULTS: Vilazodone-treated patients had significantly greater improvement (P = .009) according to the MADRS than placebo patients (intent-to-treat; least-squares mean changes: -13.3, -10.8). MADRS response rates were significantly higher with vilazodone than placebo (44% vs 30%, P = .002). Remission rates for vilazodone were not significantly different based on the MADRS (vilazodone, 27.3% vs placebo, 20.3%; P = .066) or HDRS-17 (vilazodone, 24.2% vs placebo, 17.7%; P = .088). Vilazodone-treated patients had significantly greater improvements from baseline in HDRS-17 (P = .026), HDRS-21 (P = .029), HARS (P = .037), CGI-S (P = .004), and CGI-I (P = .004) scores than placebo patients. Rates of discontinuation due to adverse events were 5.1% (vilazodone) and 1.7% (placebo). The most common adverse events (vilazodone vs placebo) were diarrhea (31% vs 11%), nausea (26% vs 6%), and headache (13% vs 10%). Treatment-related effects on sexual function as measured by the CSFQ were small and similar to placebo. Effects on weight were no different from placebo. CONCLUSIONS: Vilazodone 40 mg/d was well tolerated and effective in adult patients with MDD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00683592.

The Safety and Tolerability Profile of Vilazodone, A Novel Antidepressant for the Treatment of Major Depressive Disorder.

OBJECTIVE: Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD). This report summarizes the safety and tolerability of vilazodone 40 mg/day during short- and long-term treatment of adult MDD. METHODS: Pooled data from two 8-week, double-blind studies of vilazodone (n = 436) vs placebo (n = 433) and data from one 52-week, open-label study (n = 616, vilazodone only) were analyzed. Patients aged 18-70 with DSM-IV-TR-defined MDD received vilazodone or placebo (8-week studies only) once daily, with food, titrated to 40 mg/day over 2 weeks. Safety and tolerability assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and weight. RESULTS: The most common AEs in all studies were diarrhea, nausea, and headache. Vilazodone-associated AEs in the two 8-week studies, defined as an incidence rate of ≥5% in the vilazodone group and at least twice that for placebo, were diarrhea (28.0% vs 9.2%), nausea (23.4% vs 5.1%), and insomnia (6.0% vs 2.1%), with the majority reported as mild to moderate and <5% of those patients requiring concomitant (directed) treatment for these conditions. Discontinuation rates due to AEs were 7.1% (vilazodone) and 3.2% (placebo) in the 8-week studies and 20.7% in the 52-week study. Vilazodone had no clinically significant effects on vital signs, laboratory tests, or electrocardiograms. CONCLUSION: Vilazodone 40 mg/day was well tolerated during short- and long-term MDD treatment in these trials. Safety profiles associated with 8- and 52-week exposure were consistent.