BACKGROUND: Vortioxetine is a recently approved multimodal antidepressant with 
anxiolytic properties in preclinical studies.
OBJECTIVE: This double-blind, placebo-controlled study assessed the efficacy and 
tolerability of vortioxetine in subjects with a primary diagnosis of generalized 
anxiety disorder.
METHODS: Subjects (n = 457) were randomized 1:1:1 to treatment with placebo or 
vortioxetine 2.5 or 10 mg once daily. The primary efficacy endpoint was 
reduction in Hamilton Anxiety Scale (HAM-A) total scores from baseline after 
8 weeks of treatment. Key secondary outcomes were changes from baseline in HAM-A 
total scores for the 2.5 and 10 mg dose, Hospital Anxiety and Depression anxiety 
subscore, 36-Item Short-Form Health Survey, Sheehan Disability Scale, and 
Clinical Global Impression-Improvement Scale score, as well as HAM-A response 
rate at week 8.
RESULTS: Neither vortioxetine dose achieved a statistically significant 
improvement over placebo on the primary endpoint (least-squares mean 
difference ± standard error from placebo: -0.87 ± 0.803 [p = 0.279] for 2.5 mg 
and -0.81 ± 0.791 [p = 0.306] for 10 mg vortioxetine) or on any secondary 
efficacy endpoints. Common adverse events (≥5% in either vortioxetine group) 
were nausea, dry mouth, headache, diarrhea, constipation, and vomiting.
CONCLUSIONS: Vortioxetine 2.5 and 10 mg treatment did not significantly improve 
generalized anxiety disorder symptoms versus placebo. Vortioxetine was safe and 
well tolerated in this patient population.