A Randomized, Double-Blind, Placebo-Controlled Trial of Vilazodone in Children and Adolescents with Major Depressive Disorder with Twenty-Six-Week Open-Label Follow-Up

Abstract

Objective: To evaluate the efficacy and long-term safety of vilazodone in children and adolescent outpatients with major depressive disorder (MDD). Methods: Children and adolescents aged 7-17 years of age with MDD were randomized 2:2:1 to 8 weeks of double-blind placebo, vilazodone 15 or 30 mg/day or fluoxetine 20 mg/day, respectively. The primary and secondary efficacy outcomes, respectively, were change from baseline to week 8 in Children's Depression Rating Scale-Revised (CDRS-R) score total score and Clinical Global Impressions-Severity (CGI-S) score analyzed using a mixed model for repeated measurement approach. Patients who completed the 8-week randomized controlled trial (RCT), as well as new (de novo) patients, could participate in a 26-week, vilazodone-only, open-label extension (OLE) study. Results: The RCT enrolled 473 patients (60% female) with an average age of 13 years. Change in CDRS-R and CGI-S scores from baseline to week 8 did not differ between patients who received vilazodone and those randomized to placebo. The least-squares mean change from baseline in CDRS-R scores was similar for vilazodone and placebo (-20.7 vs. -20.3, p = 0.77; least-squares mean difference [LSMD] = -0.40). For fluoxetine, the LSMD versus placebo was -2.3 (p = 0.14). The OLE enrolled 330 patients (60% female) with an average age of 13-14 years. Overall, no new safety concerns were identified compared to what is known in adults. Conclusions: Similar improvements in depressive symptoms were observed in all arms. This study does not support the efficacy of vilazodone 15 or 30 mg/day for pediatric patients with MDD. No new or unexpected safety concerns were detected during the RCT or OLE studies.

Keywords: adolescents; children; clinical trial; major depressive disorder; treatment efficacy; vilazodone.

FIG. 1.

Study flow and patient disposition. N, number of screened patients; n, number of patients within a specific category; PBO, placebo; VLZ, vilazodone; FLX, fluoxetine; WOC, withdrawal of consent; ITT, intent-to-treat; AE, adverse event; ITR, insufficient therapeutic response; LTFU, lost to follow-up; PV, protocol violation; NC, noncompliance; LOE, lack of efficacy.

FIG. 2.

Change from baseline in CDRS-R total score in the randomized controlled trial (MMRM, ITT population). CDRS-R, Children's Depression Rating Scale-Revised; MMRM, mixed-effects model for repeated measures; ITT, intent-to-treat; LS mean, least squares mean; SD, standard deviation; PBO, placebo; VLZ, vilazodone; FLX, fluoxetine.

FIG. 3.

Change from baseline in CDRS-R total score-by-visit in the open-label extension study (MMRM, ITT population). CDRS-R, Children's Depression Rating Scale-Revised; MMRM, mixed-effects model for repeated measures; ITT, intent-to-treat; LS mean, least-squares mean; PBO, placebo; VLZ, vilazodone; FLX, fluoxetine.