title: A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine.
abstract: OBJECTIVE
  This randomised, double-blind, 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine(10-20 mg/day) versus agomelatine (25-50 mg/day) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline reuptake inhibitor (SNRI) monotherapy.
  
  
  METHODS
  Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine. Primary endpoint was change from baseline to week 8 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score analysed by mixed model for repeated measurements, using a noninferiority test followed by a superiority test. Secondary endpoints included response and remission rates, anxiety symptoms(Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life(EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale).
  
  
  RESULTS
  Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p<0.01). Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12; MADRS, Hamilton Anxiety Rating Scale, Clinical Global Impression, Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards; work limitation questionnaire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12. Fewer patients withdrew because of adverse events with vortioxetine (5.9% vs 9.5%). Adverse events (incidence ≥5%) were nausea, headache, dizziness and somnolence.
  
  
  CONCLUSIONS
  Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy. Vortioxetine was safe and well tolerated.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Montgomery
authors.forename: Rebecca Z
authors.initials: RZ
authors.lastname: Nielsen
authors.forename: Lis H
authors.initials: LH
authors.lastname: Poulsen
authors.forename: Lars
authors.initials: L
authors.lastname: Häggström
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013440:Sulfides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000078784:Vortioxetine; D055815:Young Adult; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine; C084711:agomelatine; D009281:Naphthalenes
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