OBJECTIVE: This article summarizes the US Food and Drug Administration's (FDA's) 
review of the New Drug Application for vortioxetine, especially the clinical 
efficacy and safety data. It emphasizes the issues that were important to the 
FDA's approval decision, particularly the difference in the effective dose in 
domestic and foreign studies, and notes several new labeling features, 
specifically, description of time course of treatment response and detailed 
sexual dysfunction evaluation.
DATA SOURCES: The data sources were the original raw data sets for all clinical 
trials included in the development program for vortioxetine, as well as the 
sponsor's original analyses of these data. Data were available from 51 human 
trials involving vortioxetine, and included a total of 7,666 healthy volunteers 
and patients with a diagnosis of major depressive disorder (MDD) or generalized 
anxiety disorder who were exposed to at least 1 dose of vortioxetine for a total 
of 2,743 patient-years.
RESULTS: Vortioxetine was effective in treating MDD in the United States at a 
dose of 20 mg/d. The recommended starting dose is 10 mg once daily without 
regard to food, with increase to 20 mg/d if the 10 mg/d dose is tolerated. For 
patients who do not tolerate 20 mg/d, 10 mg/d can be used and 5-mg/d dose can be 
considered. Vortioxetine can be discontinued abruptly, but it is recommended 
that doses of 15 mg/d or 20 mg/d be reduced to 10 mg/d for 1 week prior to full 
discontinuation to avoid potential withdrawal symptoms. Although the non-US 
maintenance study showed that maintenance doses of 5 to 10 mg/d were effective, 
a clinical judgment needs to be made to decide the maintenance dose in the 
United States. The applicant has agreed to conduct a US maintenance 
dose-response study covering the US-approved dose range. Vortioxetine's adverse 
event profile is similar to that of other selective serotonin reuptake 
inhibitors (SSRIs). Nausea is the most common adverse event and is dose 
dependent. No dose adjustment is needed based on age, gender, or the presence of 
renal or mild to moderate hepatic impairment. The maximum recommended dose is 10 
mg/d in known cytochrome P450 2D6 poor metabolizers.
CONCLUSIONS: Vortioxetine is a new treatment for MDD, and its adverse event 
profile is similar to that of other SSRIs.