title: A meta-analysis of the efficacy of vortioxetine in patients with major depressive disorder (MDD) and high levels of anxiety symptoms.
abstract: Coexisting anxiety is common in major depressive disorder (MDD) and more difficult to treat than depression without anxiety. This analysis assessed the efficacy, safety, and tolerability of vortioxetine in MDD patients with high levels of anxiety (baseline Hamilton Anxiety Rating Scale [HAM-A] total score ≥20).
  
  
  
  Efficacy was assessed using an aggregated, study-level meta-analysis of 10 randomized, placebo-controlled, 6/8-week trials of vortioxetine 5-20mg/day in adults (18-75 years), with a study in elderly patients (≥65 years) analyzed separately. Outcome measures included mean differences from placebo in change from baseline to endpoint (Δ) in the Montgomery-Åsberg Depression Rating Scale (MADRS), HAM-A total, and HAM-A subscales. Safety and tolerability were assessed by treatment-emergent adverse events (TEAEs).
  
  
  
  A total of 1497 (48.6%) vortioxetine-treated and 860 (49.1%) placebo-treated patients had baseline HAM-A≥20. There were significant differences from placebo in MADRS (vortioxetine 5mg/day, n=415, Δ-2.68, P=0.005; 10mg/day, n=373, Δ-3.59, P<0.001; 20mg/day, n=207, Δ-4.30, P=0.005) and HAM-A total (5mg/day, n=419, Δ-1.64, P=0.022; 10mg/day, n=373, Δ-2.04, P=0.003; 20mg/day, n=207, Δ-2.19, P=0.027). There were significantly greater improvements versus placebo on the HAM-A psychic subscale for all doses. The most common TEAEs (≥5.0%) were nausea, headache, dizziness, dry mouth, diarrhea, nasopharyngitis, constipation, and vomiting. Incidence of serious TEAEs was 1.3% (placebo) and ≤1.3% (vortioxetine, across doses).
  
  
  
  Study heterogeneity limits this analysis. Patients with baseline HAM-A≥20 were not directly compared to baseline HAM-A<20 or total MDD population.
  
  
  
  Vortioxetine was efficacious in reducing depressive and anxiety symptoms in patients with MDD and high levels of anxiety.
authors.affiliation: University Department of Psychiatry, Southampton, UK; University Department of Psychiatry and Mental Health, University of Cape Town, South Africa. Electronic address: D.S.Baldwin@soton.ac.uk.
authors.forename: David S
authors.initials: DS
authors.lastname: Baldwin
authors.affiliation: H. Lundbeck A/S, Copenhagen, DK.
authors.forename: Ioana
authors.initials: I
authors.lastname: Florea
authors.affiliation: Takeda Development Center Americas, Deerfield, IL, USA.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Jacobsen
authors.affiliation: Takeda Development Center Americas, Deerfield, IL, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Takeda Development Center Americas, Deerfield, IL, USA.
authors.forename: George G
authors.initials: GG
authors.lastname: Nomikos
mesh_terms: D001007:Anxiety / Q000523:psychology*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D003967:Diarrhea / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D006261:Headache / Q000139:chemically induced; D006801:Humans; D009304:Nasopharyngitis / Q000139:chemically induced; D009325:Nausea / Q000139:chemically induced; D010879:Piperazines / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013440:Sulfides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000078784:Vortioxetine; D014987:Xerostomia / Q000139:chemically induced
chemical_list: D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine
keywords: Anxiety symptoms; Major depressive disorder; Multimodal antidepressant; Serotonin receptor; Serotonin transporter; Vortioxetine