title: Vortioxetine (Lu AA21004) in the long-term open-label treatment of major depressive disorder.
abstract: OBJECTIVE
  The primary objective of this study was to evaluate the safety and tolerability of the investigational drug vortioxetine (Lu AA21004) in the long-term treatment of patients with major depressive disorder.
  
  
  METHODS
  Patients entered this 52-week, open-label extension study after completing an 8-week lead-in study. Safety and tolerability were evaluated at regular intervals on the basis of spontaneously reported adverse events (AEs), clinical safety laboratory tests, vital signs, ECG and physical examination. Effectiveness of treatment was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.
  
  
  RESULTS
  A total of 535 patients were treated and 61.3% (n = 328) completed the study, resulting in 393 patient years of exposure to vortioxetine. AEs reported by ≥10% of patients were nausea, headache, and nasopharyngitis. Taken together, six patients had eight AEs related to sexual dysfunction. There were no clinically significant safety findings with respect to mean changes of vital signs, weight, ECG parameters, or clinical laboratory values. Patients entered the extension study with a mean MADRS total score of 13.5 ± 8.7. The mean MADRS total score decreased (improved) by approximately 8 points to 5.5 ± 6.0 at Week 52 (OC). By the end of the study, the proportion of responders had increased from 63% to 94% (OC), as had the proportion in remission (MADRS ≤10), increasing from 42% to 83% (OC). Patients in remission (n = 226) at the start of this study had a relapse rate (MADRS ≥22) of 9.7%.
  
  
  CONCLUSIONS
  As with all open-label studies, the conclusions that can be drawn are limited by the lack of a placebo control, making it difficult to assess causality of any changes in outcome measures. However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment.
  
  
  BACKGROUND
  This study has the ClinicalTrials.gov identifier: NCT00694304.
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, United Kingdom. dsb1@soton.ac.uk
authors.forename: David S
authors.initials: DS
authors.lastname: Baldwin
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.forename: Ioana
authors.initials: I
authors.lastname: Florea
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D006261:Headache / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009304:Nasopharyngitis / Q000139:chemically induced / Q000503:physiopathology; D009325:Nausea / Q000139:chemically induced / Q000503:physiopathology; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects*; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced / Q000503:physiopathology; D013440:Sulfides / Q000008:administration & dosage* / Q000009:adverse effects*; D000078784:Vortioxetine
chemical_list: D010879:Piperazines; D013440:Sulfides; D000078784:Vortioxetine