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 p = .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.

Plain language summary

This global study evaluated the efficacy, safety, and tolerability of vortioxetine in children aged 7-11 years with major depressive disorder (MDD). Those who did not improve after 4 weeks of initial treatment with placebo and psychotherapy (540 children) were randomly assigned to a placebo, vortioxetine 10-mg/d, or vortioxetine 20-mg/d for 8 weeks and psychotherapy. The primary measure was the change in depressive symptoms using the Children’s Depression Rating Scale-Revised (CDRS-R); children on vortioxetine showed a slight improvement in CDRS-R total scores compared to those on placebo. Vortioxetine (average of 10-mg/d and 20-mg doses/d) was not more effective than placebo (mean difference of –2.1 points; p = 0.0937). Safety and tolerability measures were similar to previous studies of adults and adolescents treated with vortioxetine, with nausea being the most common adverse effect in the vortioxetine groups (11.1% among participants receiving vortioxetine 20-mg/d and 12.6% among participants receiving vortioxetine 10-mg/d).

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.