Vortioxetine for Major Depressive Disorder in Children: 12-Week Randomized, Placebo-Controlled Study.

Objective: To evaluate efficacy, safety, and tolerability of vortioxetine in children ages 7 to 11 years with major depressive disorder.

Method: Patients meeting criteria for incomplete improvement in depressive symptoms (Children's Depression Rating Scale-Revised [CDRS-R] total score ≥40 plus <40% reduction and Parent Global Assessment Global Improvement score >2) after 4 weeks of single-blind lead-in treatment with a brief psychosocial intervention plus placebo were randomized 1:1:1:1 to 8-week double-blind treatment with brief psychosocial intervention and placebo, vortioxetine 10 mg/day, vortioxetine 20 mg/day, or fluoxetine 20 mg/day. Following preplanned interim analysis, enrollment to fluoxetine was stopped, and patients were randomized 1:1:1 to placebo, vortioxetine 10 mg, or vortioxetine 20 mg. The primary end point was change in CDRS-R total score from baseline to week 8 for average of vortioxetine 10-mg and 20-mg doses vs placebo.

Results: Of 683 patients enrolled in single-blind lead-in treatment, 540 were randomized to the double-blind period. The mean (SE) change from randomization to week 8 in CDRS-R total score for average of vortioxetine 10-mg and 20-mg doses vs placebo was -19.6 (1.2) and -17.5 (1.4), with a mean difference of -2.1 (1.2) (2-sided = .0937). Overall, 47% of patients reported treatment-emergent adverse events in the double-blind period; nausea was the most common adverse event in the vortioxetine groups (11.1%-12.6%).

Conclusion: No statistically significant differences were observed in improvement in CDRS-R total score between placebo and vortioxetine; hence, efficacy of vortioxetine for treatment of major depressive disorder in children could not be confirmed. Safety and tolerability data were similar to that seen in adolescents and adults, with no outstanding safety concerns.

Clinical Trial Registration Information: Active Reference (Fluoxetine) Fixed-dose Study of Vortioxetine in Paediatric Participants Aged 7 to 11 Years With Major Depressive Disorder (MDD); https://clinicaltrials.gov/study/NCT02709655.