Abstract
To evaluate the efficacy and safety of vortioxetine in adolescents with major depressive disorder (MDD). 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. 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. 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. 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.
Highlights
Major Depressive Disorder (MDD) (DSM-5) who did not meet response criteria (Children’s Depression Rating Scale–Revised [CDRS-R]; total score 40 plus 2) were randomized 1:1:1:1 to 8 weeks of Brief Psychosocial Intervention (BPI) plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg, or placebo
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
Pediatric studies evaluating the efficacy of antidepressants have generally been faced with the challenge of high placebo response rates, with several studies failing to demonstrate separation from placebo.[3,4,5,6,7,8,9]
Summary
Safety analyses included all patients randomized to the 8week treatment period who received at least 1 tablet of vortioxetine, fluoxetine, or placebo (treated patients); treatment-emergent AEs (TEAEs) were summarized using descriptive statistics. Efficacy analyses included all treated patients with a valid CDRS-R total score assessment at randomization and at least 1 valid CDRS-R total score postrandomization assessment (the full analysis set [FAS]). The primary efficacy endpoint assessing the changes from randomization in CDRS-R total score to week 8 averaged for the 2 vortioxetine doses of 10 mg and 20 mg was analyzed by using a mixed model for repeated measurements (MMRM) with freely varying mean and covariance structures, and included the fixed categorical effects of treatment, country, and week, and the continuous covariates of CDRS-R total score at randomization, treatment-by-week interaction, and CDRSR at randomization-by-week interaction.
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