Vortioxetine for Major Depressive Disorder in Adolescents: 12-Week Randomized, Placebo-Controlled, Fluoxetine-Referenced, Fixed-Dose Study

Objective: To evaluate the efficacy and safety of vortioxetine in adolescents with major depressive disorder (MDD). Method: After 4 weeks of single-blind lead-in treatment with a Brief Psychosocial Intervention (BPI) plus placebo, patients (aged 12−17 years) with MDD (DSM-5) who did not meet response criteria (Children's Depression Rating Scale–Revised [CDRS-R]; total score ≥40 plus <40% reduction and a Parent Global Assessment score >2) were randomized 1:1:1:1 to 8 weeks of BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg, or placebo. The primary endpoint was change from randomization in CDRS-R total score at week 8; the primary comparison was the average effect of 2 vortioxetine doses vs placebo. Results: Of 784 patients enrolled in the lead-in, 616 were randomized. At week 8, the mean change in CDRS-R total score averaged for vortioxetine doses was –18.01 (SE = 0.98) and the mean difference vs placebo was 0.21 (P = .878; not significant). For fluoxetine, the mean change in CDRS-R total score was –21.95 and the mean difference vs placebo was –3.73 (P = .015). Treatment-emergent adverse events occurring in ≥5% of patients in either vortioxetine arm and at least twice more frequently than placebo were nausea, headache, vomiting, and dizziness. Conclusion: Patients in all groups showed reduction in CDRS-R scores by the end of the study, with no difference between combined doses of vortioxetine and placebo. The primary endpoint was not met, thereby rendering the study negative. The overall favorable safety profile of vortioxetine in an adolescent patient population was consistent with that seen in adults. Clinical trial registration information: Active Reference (Fluoxetine) Fixed-Dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD); http://clinicaltrials.gov; NCT02709746.