title: Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis.
abstract: Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning.
  
  
  
  Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5-20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted.
  
  
  
  TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low.
  
  
  
  Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.
authors.affiliation: 1Takeda Development Center Americas,Deerfield,Illinois,USA.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Jacobsen
authors.affiliation: 1Takeda Development Center Americas,Deerfield,Illinois,USA.
authors.forename: Atul R
authors.initials: AR
authors.lastname: Mahableshwarkar
authors.affiliation: 1Takeda Development Center Americas,Deerfield,Illinois,USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Palo
authors.affiliation: 1Takeda Development Center Americas,Deerfield,Illinois,USA.
authors.forename: Yinzhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 2H. Lundbeck A/S,Copenhagen,Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Dragheim
authors.affiliation: 3Department of Psychiatry and Neurobehavioral Sciences,University of Virginia,Charlottesville,Virginia,USA.
authors.forename: Anita H
authors.initials: AH
authors.lastname: Clayton
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced*; D020018:Sexual Dysfunctions, Psychological / Q000139:chemically induced*; D013440:Sulfides / Q000009:adverse effects*; D000078784:Vortioxetine
chemical_list: D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine
keywords: Antidepressant; Arizona Sexual Experiences Scale (ASEX); generalized anxiety disorder (GAD); major depressive disorder (MDD); selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine reuptake inhibitors (SNRIs); sexual adverse events; vortioxetine