title: The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.
abstract: The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder.
authors: Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK University Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa dsb1@soton.ac.uk.
authors: David S
authors: DS
authors: Baldwin
authors: Takeda Development Center Americas, Deerfield, IL, USA.
authors: Lambros
authors: L
authors: Chrones
authors: H Lundbeck A/S, Copenhagen, Denmark.
authors: Ioana
authors: I
authors: Florea
authors: H Lundbeck A/S, Copenhagen, Denmark.
authors: Rebecca
authors: R
authors: Nielsen
authors: Takeda Development Center Americas, Deerfield, IL, USA.
authors: George G
authors: GG
authors: Nomikos
authors: Takeda Development Center Americas, Deerfield, IL, USA.
authors: William
authors: W
authors: Palo
authors: H Lundbeck A/S, Copenhagen, Denmark.
authors: Elin
authors: E
authors: Reines
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D013440:Sulfides / Q000009:adverse effects* / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D000078784:Vortioxetine; D055815:Young Adult
chemical_list: D000068736:Duloxetine Hydrochloride; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000069470:Venlafaxine Hydrochloride; D000078784:Vortioxetine
keywords: Major depressive disorder; safety; tolerability; vortioxetine