Vortioxetine (Lu AA21004) in generalized anxiety disorder: Results of an 8-week, multinational, randomized, double-blind, placebo-controlled clinical trial Leszek Bidzan a , Atul R. Mahableshwarkar b , Paula Jacobsen b , Mingjin Yan b , David V. Sheehan c,n a Department of Developmental, Psychotic, and Geriatric Psychiatry, Medical University of Gdansk, Gda  nsk, Poland b Takeda Global Research & Development Inc., Deerfield, IL, USA c University of South Florida, College of Medicine, Tampa, FL, USA Received 2 April 2012; received in revised form 20 June 2012; accepted 19 July 2012 KEYWORDS Generalized anxiety disorder (GAD); Multimodal; Bis-aryl-sulfanyla- mine; Major depressive disorder (MDD) Abstract Vortioxetine is a multimodal antidepressant, with anxiolytic properties observed in preclinical studies. The goal of the current study was to evaluate the efficacy and tolerability of vortioxetine 5 mg vs placebo in adults with generalized anxiety disorder (GAD). Adults with a primary diagnosis of GAD (HAM-A total score Z20 and MADRS score r16) received vortioxetine 5 mg or placebo for 8 weeks. The primary efficacy endpoint was reduction in HAM-A total scores from baseline after 8 weeks of treatment compared with placebo. Key secondary measurements were HAD anxiety subscore, CGI-I, SDS total score, HAM-A response rates, HAM-A total score for subjects whose baseline HAM-A total score was Z25, and SF-36 social functioning subscore. HAM-A remission rates were also measured. Adverse events (AEs) were assessed throughout the study. In total, 301 subjects (mean age, 45.2 years; 31% male) were randomized (1:1) to receive vortioxetine 5 mg (n =150) or placebo (n =151). After 8 weeks of treatment, there was a statistically significant difference in reduction from baseline in HAM-A total score for the vortioxetine group (14.30) compared with placebo recipients (10.49) (Po0.001). Statisti- cally significant differences were observed for all key secondary outcomes favoring vortioxetine treatment (vs placebo), using a mixed model for repeated measurements (MMRM) analysis. Active treatment resulted in a significantly higher rate of remission. Vortioxetine was well tolerated. The most common treatment-related AEs were nausea, headache, dizziness, and dry mouth. In sum, vortioxetine was safe and effective in treating adults with GAD in this multinational population. & 2012 Elsevier B.V. and ECNP. All rights reserved. www.elsevier.com/locate/euroneuro 0924-977X/$ - see front matter & 2012 Elsevier B.V. and ECNP. All rights reserved. http://dx.doi.org/10.1016/j.euroneuro.2012.07.012 n Corresponding author. E-mail address: dsheehan@health.usf.edu (D.V. Sheehan). European Neuropsychopharmacology (2012) 22, 847–857