Psychiatry and clinical neurosciences 2017 11 21() doi 10.1111/pcn.12623
Safety and efficacy of vortioxetine (5-20 mg/day) in Japanese patients with major depressive disorder were evaluated in two phase 3 studies consisting of a short-term, 8-week, placebo-controlled, double-blind study followed by a long-term, 52-week, open-label extension study.
The primary endpoint of the short-term study was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8. The primary objective of the extension study was vortioxetine’s long-term safety; efficacy endpoints included change in MADRS total score, clinical global impression scale-severity (CGI-S) score from the long-term study baseline, and clinical global impression scale-improvement (CGI-I) score over 52 weeks.
Of the 366 randomized patients, 338 completed the short-term study, and 119 patients continued into the extension study. Primary (analysis of covariance [ANCOVA]) and secondary (mixed model for repeated measurements [MMRM]) analyses in the short-term study showed numerically greater, but not statistically significant, decreases in change in MADRS total score from baseline between vortioxetine and placebo groups at week 8. In the long-term study, 86.6% of patients reported at least 1 treatment-emergent adverse event (TEAE), with most common being nasopharyngitis (40.3%) and nausea (21%). MADRS total score and CGI-I and CGI-S scores improved with continued vortioxetine treatment from baseline of the open-label study to week 52.
Vortioxetine failed to meet significance versus placebo in the primary efficacy analysis at week 8 in the short term-study. The extension trial indicated continued improvement of depressive symptoms from baseline of this study throughout the 52-week treatment period. Vortioxetine treatment was safe and well tolerated in both studies.
The short-term study has the ClinicalTrials.gov identifier NCT01355081; the open-label, long-term extension trial has the ClinicalTrials.gov identifier NCT01395147.