• Mood Disorders
• Psychiatry Clinical Trials
• Psychopharmacology

• Mood Disorders
• Psychiatry Clinical Trials
• Psychiatry
• Psychopharmacology

A multicenter, randomized, double-blind, placebo-controlled trial involving more than 1100 patients with major depressive disorder (MDD) has affirmed the efficacy and safety of vilazodone (VLZ) 40 mg/day and indicated the acceptability of a dose of 20 mg/day. The poster presenter was Carl Gommoll, MS, Forest Research Institute, Jersey City New Jersey, USA [APA 2014 (poster NR6–103)].

VLZ is a selective serotonin (5-HT) reuptake inhibitor and partial agonist of the 5-HT_1A receptor. Two prior placebo-controlled Phase 3 trials reported the efficacy and safety of a 40-mg/day dose [Khan A et al. J Clin Psychiatry 2011; Rickeis K et al. J Clin Psychiatry 2009]. Researchers of a 52-week open-label study reported the long-term safety and tolerability of the same dose [Robinson DS et al. J Clin Psychopharmocol 2011].

The current study [NCT01473381] was conducted to confirm the results using this now-approved dose, as well as to assess the effectiveness, safety, and tolerability of a lower dose of 20 mg/day. The study was placebo-controlled and incorporated Citalopram (CIT) 40 mg/day as an active control for assay sensitivity. The study phases consisted of a 1- to 4-week drug-free screening period, 10-week double-blind treatment, and 1-week double-blind down-taper. The 1162 patients were randomly assigned 1:1:1:1 to receive placebo, VLZ 20 mg/day, VLZ 40 mg/day, or CIT 40 mg/day, respectively.

Included patients were aged 18 to 70 years, met DSM-IV-TR criteria for MDD and had ongoing major depressive episodes, had Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥26 at screening and baseline, and were physically sound. Exclusion criteria included DSM-IV-TR-defined Axis I disorder other than MDD within the prior 6 months (excepting secondary diagnoses of comorbid generalized anxiety disorder, social anxiety, and/or specific phobia), defined suicide risk, absence of effect of ≥2 antidepressant drugs, and recent (within 2 weeks) use of psychoactive drugs or need for treatment with eszopiclone, zopiclone, or zaleplon.

The primary efficacy measure was MADRS total score. Secondary efficacy measures were Clinical Global Impressions-Severity (CGI-S) score and MADRS sustained response rate (≤12 for at least the last two clinic visits during the treatment period). CGI-Improvement and Hamilton Rating Scale for Anxiety (HAM-A) scores were also determined. Safety outcomes were adverse events, patient-monitored parameters, and ratings of suicidal ideation and sexual functioning.

The safety population comprised 281 placebo, 288 VLZ 20mg, 287 VLZ 40 mg, and 282 CIT patients. Patient demographics were generally similar between the groups. Approximately 70% of patients completed the study. The rate of discontinuation was significantly higher in the VLZ 40-mg/day group (34%) compared with the placebo (25%) group.

Compared with placebo, MADRS score improvement from baseline to Week 10 was significantly greater for VLZ 20 mg (least squares mean difference [LSMD], −2.57; adjusted p=0.0073) and VLZ 40 mg (LSMD, −2.82; adjusted p=0.0034) in the intent-to-treat population. CIT versus placebo had a similar pattern (LSMD, −2.74; p=0.0020), demonstrating assay sensitivity. In the same population, reductions in CGI-S scores were significantly greater than placebo for VLZ 20 mg (LSMD, −0.35; adjusted p=0.0073), VLZ 40 mg (LSMD,-0.33; adjusted p=0.0097), and CIT (LSMD, −0.35; p=0.0025). More patients met criteria for MADRS sustained response in the VLZ 20-mg (29.9%), VLZ 40-mg (33.5%), and CIT (31.1%) groups versus the placebo (26.3%) group; differences were not statistically significant.

All groups displayed similar adverse event (AE) profiles. Rates of treatment-emergent AEs (TEAEs) were similar for VLZ 20 mg (72.2%), VLZ 40 mg (77.4%), CIT (77.0%), and placebo (63.3%). TEAEs occurring in ≥5% of VLZ patients and twice placebo were diarrhea, nausea, vomiting, and insomnia. Majority of TEAEs were mild or moderate in severity. Serious AEs were reported in 2 placebo, 4 VLZ 20-mg, 4 VLZ 40-mg, and 6 CIT patients. One death occurred, in a patient receiving VLZ, which was not related to medication.

The data bolster support for the efficacy, safety, and tolerability of VLZ 40-mg/day and indicate the utility of the 20-mg/day dose.

• © 2014 MD Conference Express®