Vortioxetine in children and adolescents with major depressive disorder: 6-month and 18-month open-label, flexible-dose, long-term extension studies.

Children and adolescents with severe or relapsing major depressive disorder (MDD) may require long-term antidepressant use, but safety and tolerability data on long-term treatment are limited. In a randomized, placebo-controlled trial in children and another in adolescents, vortioxetine and placebo groups showed improvement in MDD symptoms without statistically significant differences between groups. To gain insights on long-term safety and tolerability of vortioxetine in pediatric patients, participants from these two studies were enrolled in two long-term extension studies: 6 months (NCT02871297) followed by another 18 months (NCT03108625). Key safety measures included adverse events (AEs) and Columbia-Suicide Severity Rating Scale (C-SSRS); effectiveness measures included depression symptom severity, cognitive function, and overall functioning. Among the 662 patients in the 6-month extension, 61% experienced a treatment-emergent AE (TEAE), with the most common being nausea (20.8%); 2.1% had a serious AE (SAE), and 6% withdrew because of TEAEs. In the following 18-month extension (n = 94), 51% of patients experienced a TEAE, with the most common being headache (13.8%); no SAEs were reported. Based on the C-SSRS, 94% and 96% of patients reported no suicidal ideation or behavior in the 6- and 18-month studies, respectively. During the extension studies, patients continued to show improvement in depressive symptoms and cognitive and overall functioning, with > 50% of patients in remission at the end of each study, regardless of study treatment in the lead-in trial. Overall, vortioxetine remained well tolerated in pediatric patients with MDD who continued in the long-term extension studies with no observed increased risk in suicidal ideation.