Efficacy and tolerability of vilazodone for major depressive disorder: evidence from phase III/IV randomized controlled trials.
ABSTRACT: Vilazodone is a new molecule approved for major depressive disorder (MDD). This report focuses on the efficacy and tolerability of vilazodone for MDD. MEDLINE, EMBASE, and Cochrane Library were searched. A total of 1,930 patients from four trials were included. A significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) total score was seen as early as week 2 (P<0.01) in vilazodone-treated patients. The results showed a higher rate of MADRS response with vilazodone compared with placebo (P<0.001). There were also greater improvements in the Hamilton Rating Scale for Anxiety as well as the Clinical Global Impressions (severity of illness and improvement of illness) scores from baseline in vilazodone-treated patients compared to placebo patients (P<0.001). Discontinuation rates due to adverse events were higher with vilazodone than placebo (P=0.0002). The most common adverse events of vilazodone were vomiting, nausea, diarrhea, insomnia, somnolence, dizziness, and dry mouth (P<0.05). Treatment-related effects on sexual function were mild compared to placebo in men (P=0.03). In conclusion, 40 mg/day of vilazodone had a rapid onset of response and showed good improvement in anxiety symptoms as well as good tolerability during short-term treatment (8-10 weeks) for MDD. Further studies should focus on the efficacy and tolerability of vilazodone over a longer duration and should utilize active comparators.
Project description:The efficacy of antidepressants to treat major depressive disorder (MDD) varies by patient characteristics. This post-hoc analysis evaluated the effects of vilazodone across patient subgroups in adults with MDD. Data were pooled from four trials of vilazodone (NCT00285376, NCT00683592, NCT01473394, and NCT01473381). Mean change from baseline to week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, MADRS response (?50% total score improvement), and MADRS remission (total score?10) were analyzed in the pooled intent-to-treat population (vilazodone=1254, placebo=964) and in subgroups of patients categorized by sex, age, MDD duration, recurrent episodes, baseline MADRS total score, and current episode duration. MADRS total score improvement was significantly greater with vilazodone versus placebo in the intent-to-treat population and in all patient subgroups (P<0.001). MADRS response and remission rates significantly separated from placebo (P<0.05) regardless of age, sex, MDD duration, recurrent MDD, and baseline symptom severity [except remission in patients with very severe baseline symptoms (MADRS score?35)] and in patients with a shorter current episode duration (?12 months). Despite the limitations associated with analyzing uncommon outcomes (e.g. MADRS remission) in small subgroups, vilazodone was an effective treatment in multiple patient populations, including those where reduced efficacy has previously been reported: males, older individuals, patients with a longer duration of MDD, and patients with recurrent depression.
Project description:Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for major depressive disorder (MDD) treatment in adults. This was a 10-week, multicenter, double-blind, placebo-controlled and active-controlled, fixed-dose trial (NCT01473381). Adult patients with MDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision criteria) were randomized 1?:?1?:?1?:?1 to vilazodone 20 or 40?mg/day, citalopram 40?mg/day, or placebo. Primary efficacy: Montgomery-Åsberg Depression Rating Scale (MADRS); secondary efficacy: Clinical Global Impressions-Severity and sustained response (MADRS total score?12 for at least the last two consecutive double-blind visits). The intent-to-treat population comprised 1133 patients, (placebo=281; vilazodone 20?mg/day=288; vilazodone 40?mg/day=284; citalopram=280). MADRS and Clinical Global Impressions-Severity score change from baseline to week 10 was significantly greater for vilazodone 20?mg/day, vilazodone 40?mg/day, and citalopram versus placebo. Sustained response rates were numerically higher, but not significantly different, in all active treatment groups versus placebo. The most common adverse events (?5% of vilazodone patients, twice the rate of placebo) were diarrhea, nausea, vomiting (vilazodone 40?mg/day only), and insomnia. Improved sexual function (Changes in Sexual Functioning Questionnaire scores) was seen in all groups; between-group differences were not significant. Vilazodone 20 and 40?mg/day demonstrated efficacy and tolerability in the treatment of MDD.
Project description:OBJECTIVE:To assess clinically relevant symptom improvement in patients with major depressive disorder (MDD) receiving vilazodone by using the Montgomery-Asberg Depression Rating Scale (MADRS), a clinician-rated scale used to measure MDD symptom severity and improvement. METHOD:Pooled data from 2 positive, phase 3, 8-week, double-blind, randomized, placebo-controlled trials in patients with MDD were analyzed. Patients received vilazodone 40 mg/d or placebo; post hoc analyses were conducted on study completers. Depression symptom improvement was evaluated by analyzing the proportions of patients who shifted from the baseline MADRS single-item symptom severity category of ? 2 (mild to severe symptoms) to an end-of-study category < 2 (minimal to no symptoms) or from ? 4 (moderate to severe symptoms) to ? 2 (mild to no symptoms). The proportion of patients who shifted from anxious depression to no anxious depression was also analyzed. RESULTS:The percentage of patients who completed these studies with severity category shift from baseline ? 2 to end of study < 2 was significantly higher for vilazodone versus placebo on all MADRS items (odds ratio [OR] range, 1.4-1.7, P < .05) except reduced appetite (OR = 1.3, P = .232). A significantly greater proportion of vilazodone-treated versus placebo-treated patients shifted from baseline ? 4 to end of study ? 2 on MADRS items of apparent sadness, reported sadness, inner tension, reduced sleep, and lassitude (OR range, 1.5-2.0, P < .05). Additionally, a significantly greater proportion of vilazodone-treated versus placebo-treated patients shifted from anxious depression at baseline to no anxious depression at end of study (OR = 1.5, P = .031). CONCLUSIONS:These results suggest that vilazodone treatment is associated with clinically relevant changes in depression symptoms in patients with MDD. TRIAL REGISTRATION:ClinicalTrials.gov identifiers: NCT00285376 and NCT00683592.
Project description:Vilazodone is a potent selective serotonin reuptake inhibitor and serotonin 1A receptor partial agonist approved for the treatment of major depressive disorder in adults. To assess the efficacy of vilazodone across a range of symptoms and severities of depression, data from two phase III, 8-week, randomized, double-blind, placebo-controlled trials were pooled for analysis. Overall improvement in depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-item Hamilton Depression Rating Scale was statistically significant (P<0.05) for vilazodone treatment compared with placebo as early as Week 1 and continued throughout double-blind treatment. Vilazodone treatment compared with placebo showed significant improvement on all 10 individual MADRS symptom items at end of treatment (P<0.01). Rates of response and remission were significantly greater in the vilazodone group relative to the placebo group, with numbers needed to treat ranging from eight to nine for response and 12-17 for remission. Between-group treatment differences in MADRS and the other outcome measures were similar among all depression subgroups, with no consistent pattern associated with depression severity. These findings support the efficacy of vilazodone across a broad range of depressive symptoms and severities for the treatment of major depressive disorder.
Project description:Major depressive disorder (MDD) is a serious illness in children and adolescents. Vilazodone is a selective serotonin reuptake inhibitor approved for MDD in adults. This study evaluated the efficacy, safety, and tolerability of vilazodone in adolescent patients, ages 12-17 years, with MDD (NCT01878292).This double-blind, randomized, placebo-controlled, parallel-group, fixed-dose study was conducted at 56 study centers in the United States and was 10 weeks in duration (a 1-week screening period, an 8-week double-blind treatment period, and a 1-week double-blind down-taper period). Outpatients with an MDD diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria were included in the study. Clinical inclusion criteria required a Children's Depression Rating Scale-Revised (CDRS-R) total score of ? 40 and Clinical Global Impressions-Severity (CGI-S) score of ? 4. Patients were randomized 1:1:1 to 8 weeks of double-blind treatment with placebo (n = 174), vilazodone 15 mg/day (n = 175), or vilazodone 30 mg/day (n = 180). The primary and secondary efficacy parameters were change from baseline to week 8 in CDRS-R total score and CGI-S score, respectively. Safety parameters included adverse events (AEs); clinical laboratory, vital sign, and electrocardiogram parameters; and the Columbia-Suicide Severity Rating Scale.Approximately 86% of patients completed double-blind treatment. There was no statistically significant difference between vilazodone 15 mg/day or 30 mg/day and placebo in change from baseline in CDRS-R score. Change in CGI-S score was not significant after adjustment for multiple comparisons. The most common treatment-emergent AEs were nausea, upper abdominal pain, vomiting, diarrhea, nasopharyngitis, headache, and dizziness. Reports of suicidal ideation (placebo, 33.3%; vilazodone 15 mg/day, 36.0%; vilazodone 30 mg/day, 31.1%) and suicidal behavior (placebo, 1.8%; vilazodone 15 mg/day, 1.1%; vilazodone 30 mg/day, 1.1%) were similar between treatment groups. There were no deaths in the study.The efficacy of vilazodone for the treatment of MDD in adolescent patients could not be confirmed in this study. Vilazodone was generally safe and well tolerated, with treatment-emergent AEs similar to those in adult patients.NCT01878292.
Project description:Vilazodone, a selective and potent 5-HT1A partial agonist and 5-HT reuptake inhibitor, has been approved for treatment of major depressive disorder (MDD) in adults. The primary objective of the study was to compare the efficacy and tolerability of switching to 3 different doses of vilazodone from an equivalent dose range of generic selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in adult subjects with MDD.This was an 8-week, randomized, double-blind, parallel-group, 3-arm trial to compare vilazodone 10 mg/d, 20 mg/d, and 40 mg/d as starting doses. Data were collected from December 2012 to December 2013. There was no washout phase, prior medications were stopped at the baseline visit, and vilazodone was started the next day in adults with MDD (DSM-IV criteria). The 10-mg/d and 20-mg/d dose was increased to 40 mg/d by week 3 and week 1, respectively, and the 40-mg/d initiation dose continued unchanged. The primary efficacy measure was change in Montgomery-Asberg Depression Rating Scale (MADRS) score between the 3 dose groups. The secondary efficacy measures were changes in Clinical Global Impressions-Severity (CGI-S), CGI-Improvement (CGI-I), and Hamilton Anxiety Rating Scale (HARS) scores. Safety measures were obtained by spontaneously reported adverse events, vital signs recording, and laboratory tests. Multivariate tests were used for statistical analysis.Seventy subjects were randomized, and 60 subjects completed the study (n = 20 in each group). Overall, there was a significant reduction in MADRS score from baseline (26.08 ± 1.1) to week 8 (9.86 ± 1.2) in the entire sample (P < .001). Similarly, there was a significant improvement in CGI-S (P < .001), CGI-I (P < .001) and HDRS (P < .001) scores from baseline to the end of the trial. There were no significant differences between the 3 vilazodone dose-initiation groups in changes in MADRS scores (P = .95) or changes in CGI-S (P = .83), CGI-I (P = .51), or HARS scores (P = .61). Dry mouth (n = 55), nausea (n = 10), and diarrhea (n = 5) were the most common side effects, with diarrhea reported in 5 subjects in the 40-mg/d initiation group. No serious adverse events were reported.The present study indicates the potential benefit of switching to vilazodone in patients with MDD who are inadequate responders to SSRIs or SNRIs. There were no meaningful differences in efficacy or tolerability between the 3 different dose-initiation strategies with vilazodone; however, diarrhea appeared to be more frequently reported with the 40-mg/d dose. Given the modest sample size, larger studies are required to confirm our findings.ClinicalTrials.gov identifiers: NCT02015546 and NCT01473381.
Project description:The aim of this study was to evaluate the efficacy of vilazodone using different definitions of remission. Post-hoc analyses were carried out using data from an 8-week, multicenter, randomized, double-blind, placebo-controlled trial of vilazodone 40?mg/day in adults with major depressive disorder (NCT01473394). The primary efficacy endpoint was a mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score; additional measures included the Clinical Global Impressions-Severity (CGI-S) and Hamilton Rating Scale for Anxiety (HAMA) scores. In addition to treatment response (MADRS?50% improvement), post-hoc analyses were carried out for remission of depressive symptoms [MADRS score?10; MADRS?5 (complete remission)], anxiety symptoms (HAMA?7), and combined depression and anxiety symptoms (MADRS/HAMA?10/?7), as well as for overall symptom severity (CGI-S=1). Odds ratios (ORs) and numbers needed to treat (NNTs) were also calculated. Significant outcomes were obtained with vilazodone versus placebo for MADRS response (50.6 vs. 33.3%, OR=2.04, P<0.001, NNT=6), remission (34.0 vs. 21.8%, OR=1.82, P=0.003, NNT=9), and complete remission (18.2 vs. 8.3%, OR=2.42, P=0.002, NNT=11). More patients receiving vilazodone rather than placebo also met remission criteria for HAMA (48.8 vs. 35.2%, OR=1.82, P=0.002, NNT=8), MADRS/HAMA (32.1 vs. 20.4%, OR=1.83, P=0.004, NNT=9), and CGI-S (24.1 vs. 11.5%, OR=2.41, P<0.001, NNT=8). Treatment with vilazodone 40?mg/day may help adult patients with major depressive disorder achieve remission of depression and/or anxiety symptoms.
Project description:Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1-5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment.
Project description:OBJECTIVES:To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD). PATIENTS AND METHODS:This was a 10-week (8-week active treatment/2-week post-treatment) randomized, double-blind, placebo- and active-controlled study (D1448C00004). Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery-Åsberg Depression Rating Scale [MADRS] total score) at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (?50% improvement) and remission (score ?8); Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions - Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI) global; and Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form percentage maximum total scores. Tolerability was assessed throughout. RESULTS:A total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward) with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346]) versus placebo (-15.61). There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37). Mixed-model repeated-measures analysis of observed-case data suggested that the primary analysis may not be robust. Most commonly reported adverse events included dry mouth, somnolence, and dizziness for quetiapine XR, and headache and nausea for escitalopram. CONCLUSION:In this study, neither quetiapine XR (150/300 mg/day) nor escitalopram (10/20 mg/day) showed significant separation from placebo. Both compounds have been shown previously to be effective in the treatment of MDD; possible reasons for this failed study are discussed. Quetiapine XR was generally well tolerated, with a profile similar to that reported previously.
Project description:Vilazodone is a selective serotonin reuptake inhibitor and a 5-HT1A receptor partial agonist that is approved for treatment of major depressive disorder in adults in the USA and Mexico. The efficacy, safety, and tolerability of vilazodone for generalized anxiety disorder (GAD) were investigated in a clinical trial (NCT01766401 ClinicalTrials.gov). Participants (18-70 years, inclusive) who met Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, criteria for GAD were randomized (1:1) to placebo or flexible-dose vilazodone (20-40 mg/day) for 8 weeks of double-blind treatment. Primary and secondary efficacy parameters were changes from baseline to week 8 in Hamilton Rating Scale for Anxiety and Sheehan Disability Scale total scores, respectively. Analysis was based on a mixed-effects model for repeated measures approach on the intent-to-treat population. The intent-to-treat population comprised 395 patients (placebo=197, vilazodone=198); 77% completed the study. The least squares mean difference in change from baseline to week 8 in the Hamilton Rating Scale for Anxiety total score was statistically significant for vilazodone versus placebo [-1.50 (-2.96, -0.04), P=0.0438]. The mean change from baseline to week 8 in the Sheehan Disability Scale total score for vilazodone versus placebo was not statistically significant. Adverse events were reported in 60% of placebo-treated and 83% of vilazodone-treated patients. This was a positive clinical trial of 20-40 mg/day vilazodone versus placebo in the treatment of GAD.