Vilazodone Superior to Placebo for Treatment of Depression

Philadelphia—Among patients with major depressive disorder (MDD), those with more severe depression have longer duration of illness, increased comorbidity and mortality, fewer spontaneous remissions, and more recurrences. A previous study indicated that drug-placebo differences in trials of antidepressant efficacy are associated with baseline severity; minimal benefits are seen in patients with moderate depression. A more recent analysis demonstrated that patients with MDD across a range of severity from mild to severe responded to treatment with antidepressants. A majority of patients with mild depression experienced difficulties in daily functioning attributable to their symptoms, a finding that, according to researchers, emphasized “a need for effective treatment across the spectrum of depressive illness severity.”

At a poster session at the APA meeting, the researchers presented findings from a post hoc analysis of data from 2 positive, placebo-controlled trials of vilazodone, a serotonin reuptake inhibitor and 5-HT_1A receptor partial agonist. The poster was titled Efficacy and Tolerability of Vilazodone in Patients with Moderate, Moderately Severe, and Severe Depression–Pooled Analyses from 2 Phase III Trials.

The trials included adults 18 to 70 years of age with MDD and a 17-item Hamilton Depression Rating Scale (HAMD₁₇) score ³22 at screening and baseline. Both trials comprised a 1-week screening period followed by an 8-week double-blind treatment period.

The primary efficacy outcome variable in both trials was the mean change in total Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline to week 8. Secondary outcome variables were change from baseline to week 8 in HAMD, Hamilton Anxiety Scale (HAMA), Clinical Global Impressions-Severity (CGI-S), and CGI-Improvement (CGI-I) score at week 8.

The safety population (n=869) included all randomized patients who received the study drug; the intent-to-treat (ITT) population included all patients in the safety population who had ≥1 postbaseline MADRS total score assessment. Efficacy analyses were based on the ITT population and safety analyses were based on the safety population.

Among patients in the safety population, 31% had moderate depression, 49% had moderately severe depression, and 20% had severe depression.

Efficacy

Pooled analyses stratified by severity of baseline depression demonstrated that vilazodone was significantly superior to placebo based in change in MADRS score from baseline to week 8 across severity subgroups. The least squares mean difference was -2.9 (95% confidence interval [CI], -5.0 to -0.9; P=.0056) in the moderate depression subgroup, -2.3 (95% CI, -4.4 to -0.2; P=.0314) in the moderately severe subgroup, and -4.1 (95% CI, -7.4 to -0.7; P=.017) in the severe subgroup.

In the moderately severe group, there were significantly greater improvements in HAMD₁₇, CGI-I, and CGI-S scores with vilazodone compared with placebo (P<.05). There were significantly greater improvements for CGI-I and CGI-S scores with vilazodone compared with placebo in the moderate depression group (P<.01).

In the moderately severe and severe depression subgroups, a significantly higher percentage of patients achieved MADRS response, defined as ³50% improvement from baseline, with vilazodone compared with placebo. In all 3 subgroups, a significantly higher percentage of vilazodone patients were responders based on CGI-I criteria.

Safety

The adverse events (AEs) profile was similar across depression severity subgroups. Common AEs included diarrhea, dizziness, dry mouth, headache, insomnia, nasopharyngitis, nausea, and upper respiratory tract infection.

In conclusion, the researchers said, “In MDD patients with any of the 3 degrees of severity, improvement based on MADRS score at end of treatment was statistically superior with vilazodone...The tolerability of vilazodone was similar in all 3 depression severity subgroups.”

This study was supported by Forest Laboratories, Inc.