Vilazodone Well Tolerated in Treatment of MDD

San Diego—Data from 2 pivotal trials of 891 patients demonstrated that vilazodone was significantly superior to placebo on all depression rating scales tested, according to results presented during a poster session at the Psych Congress. The poster was titled Efficacy and Clinical Relevance of Vilazodone in the Treatment of Major Depressive Disorder: A Pooled Analysis of Phase III Clinical Trials.

The study’s aim was to evaluate the efficacy and safety of pooled data from 2 short-term, phase 3 studies of vilazodone in major depressive disorder (MDD). Efficacy across depression symptoms was determined using the Montgomery-Asberg Depression Rating Scale (MADRS) total score and single items. The clinical relevance of results was assessed using number needed to treat (NNT) and harm (NNH) analyses.

Data were culled from 2 double-blind, 8-week, randomized, placebo-controlled trials in MDD (randomized control trial [RCT] 1 and RCT 2). The studies comprised a washout period of at least 2 weeks (depending on prior therapy), a 1-week screening, and an 8-week double-blind treatment period. Patients were randomly assigned in a 1:1 ratio to vilazodone 40 mg (n=445) or placebo (n=446). Vilazodone was titrated to 40 mg (10 mg once daily for 7 days, 20 mg once daily for the next 7 days, and 40 mg once daily thereafter) and taken with food.

Patients 18 to 65 years of age (RCT 1) or 18 to 70 years of age (RCT 2) who met the diagnostic criteria for MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) were included. Patients’ current major depressive episode range was ≥4 and ≤2 years’ duration and a score ≥22 on the 17-item Hamilton Depression Rating Scale at screening and baseline.

Exclusion criteria included history of schizophrenia, schizophrenic disorder, or bipolar disorder; MDD with postpartum onset, psychotic features, or seasonal pattern; and DSM-IV-TR substance abuse or substance dependence within 3 to 6 months of screening. Patients with comorbid conditions that might interfere with trial participation were also excluded.

The primary outcome measure was total score change from baseline to week 8 on the MADRS. Post hoc analyses evaluated change from baseline on MADRS single items; and the NTT for response (≥50% improvement; clinical global impression scale ≤2) and remission (MADRS ≤10; MADRS ≤12). The NNH for adverse events (AEs) and discontinuation due to AEs was also evaluated.

Pooled analysis demonstrated significant improvement on MADRS total score from baseline to the end of week 8 for patients treated with vilazodone versus placebo (least squares mean difference [LSMD] −2.8; 95% confidence interval [CI], −4.1 to 1.4; P<.0001). A significantly greater proportion of vilazodone patients relative to placebo met response criteria (42% vs 29%, respectively; P=.0002). Remission rates (MADRS ≤10) were also considerably higher in the vilazodone group compared with placebo (29% vs 20%, respectively; P=.0041). Significant improvement for vilazodone versus placebo occurred on all MADRS single items including apparent sadness, reduced sleep, and inability to feel (LSMD −0.24, −0.30, and −0.25; respectively). The NNT for response and remission were 8 (95% CI, 5-17) and 12 (95% CI, 7-37), respectively. The NNH for discontinuation due to AEs was 26 (95% CI, 15-106).

“Vilazodone showed broad efficacy across depression symptoms,” concluded the investigators. “The NNT for response versus placebo was ≤10 suggesting clinically relevant improvement; risk of AE discontinuation with vilazodone was low relative to clinically meaningful benefits on depressive symptoms.”

This study was supported by Forest Laboratories, Inc.