Evidence for Efficacy and Tolerability of Vilazodone in the Treatment of Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

Karl Rickels, M.D.; Maria Athanasiou, Ph.D.; Donald S. Robinson, M.D.; Michael Gibertini, Ph.D.; Heidi Whalen, M.H.S.; and Carol R. Reed, M.D.

Objective: The efficacy and tolerability of vilazodone, a combined selective serotonin reuptake inhibitor and partial 5-hydroxytryptamine-1A (5-HT_1A) receptor agonist, were evaluated in adult patients with major depressive disorder (MDD).

Method: This was a randomized, double-blind, placebo-controlled trial conducted from February 2006 to May 2007. Patients aged 18 through 65 years with MDD (DSM-IV criteria) and a baseline 17-item Hamilton Rating Scale for Depression (HAM-D-17) score of ≥22 were randomly assigned to vilazodone or placebo for 8 weeks. Vilazodone was titrated from 10 mg to 40 mg once a day over 2 weeks. Efficacy was assessed by mean change from baseline to week 8 on the Montgomery-Asberg Depression Rating Scale (MADRS), HAM-D-17, and Hamilton Rating Scale for Anxiety. Response rates were determined at week 8 for the MADRS, HAM-D-17, and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. Data were analyzed using a modified last-observation-carried-forward method in the intention-to-treat (ITT) sample. The Arizona Sexual Experience Scale (ASEX) was also measured at baseline and week 8.

Results: Of 410 randomly assigned patients, 198 receiving vilazodone and 199 receiving placebo were included in the ITT population. The mean changes in MADRS and HAM-D-17 total scores from baseline to week 8 were significantly (p =.001 and p =.022, respectively) greater with vilazodone than with placebo. Significant (p <.05) improvements in MADRS and HAM-D-17 scores were noted at week 1, the earliest time point measured. Response rates were significantly higher with vilazodone than with placebo on the MADRS (p =.007), HAM-D-17 (p =.011), and CGI-I (p =.001). Treatment-emergent adverse events with vilazodone included diarrhea, nausea, and somnolence; most adverse events were of mild or moderate intensity. There were no clinically significant differences for either gender in ASEX scores at end of treatment.

Conclusion: Vilazodone is effective for the treatment of MDD in adults, with symptom relief starting at 1 week, and is well tolerated at a dose of 40 mg/day.

Trial Registration: clinicaltrials.gov Identifier: NCT00285376

(J Clin Psychiatry 2009;70(3):326-333. Online Ahead of Print March 10, 2009. doi:10.4088/JCP.08m04637)