A 6-Month Open-Label Extension Study of Vortioxetine in Pediatric Patients with Depressive or Anxiety Disorders

Abstract

Objectives: In this 6-month open-label extension (OLE) of NCT01491035 (a 14-day, open-label, pharmacokinetic/safety lead-in study), the long-term safety and tolerability of vortioxetine (5–20 mg/day) were investigated in children and adolescents with a DSM-IV-TR™ diagnosis of depressive or anxiety disorder in the United States or Germany. The study also was designed to provide data to inform dose selection and titration in future pediatric studies with vortioxetine.Methods: Safety evaluations included spontaneously reported adverse events (AEs), the Columbia Suicide Severity Rating Scale (C-SSRS), and the Pediatric Adverse Events Rating Scale (PAERS; clinician administered). Clinical effectiveness was determined by Clinical Global Impressions. Comorbid attention-deficit/hyperactivity disorder was permitted, including concomitant use of stimulant medication (US sites only).Results: Of the 47 patients who completed the lead-in period, 41 continued into the OLE. Most patients (n = 39 [95%]) continued their previous dose regimen. Twenty-one patients (51%) withdrew during the OLE; the most common primary reasons were administrative [n = 8], AEs [n = 4], and lack of efficacy [n = 3]. Thirty-five patients (85%) had ≥1 AE, 86% of which were mild or moderate in severity. Five patients (12%) reported a severe AE, none of which was considered related to study medication. The most common AEs (≥10%) were headache (27%), nausea (20%), dysmenorrhea (females; 19%), and vomiting (15%), with no relationship between AE intensity and age or dose. Five patients reported instances of suicidal ideation during the OLE, one of whom also reported this during the lead-in period. Two patients had nonsuicidal self-injurious behavior; one had a nonfatal suicide attempt. Throughout the study, there was a decrease over time in the incidence and intensity of AEs collected using the PAERS. Effectiveness assessment indicated a trend toward improvement based on numeric results.Conclusion: This OLE confirms the findings from the lead-in study, which concluded that a dosing strategy of 5–20 mg/day is safe, well tolerated, and suitable for future clinical studies of vortioxetine in pediatric patients.

Vortioxetine for Major Depressive Disorder in Adolescents: 12-Week Randomized, Placebo-Controlled, Fluoxetine-Referenced, Fixed-Dose Study

“…16 This study confirmed that vortioxetine steady-state exposure with both doses was comparable to that observed in adult populations. 16,32 This study supported the acceptable safety profile of vortioxetine previously seen in an adolescent MDD population, 16,25 with nausea as the most common AE, as seen in adult patient populations. 11 Variability in the incidence of specific AEs compared with adult populations, most specifically, suicide-related events, might be expected based on the elevated risk of suicide-related behavior versus placebo observed in pediatric MDD trials.…”

“…The selected doses of vortioxetine 10 and 20 mg/day in the double-blind treatment period were based on an open-label pediatric PK study showing PK (as assessed by Cmax and AUC0- 24) and safety/tolerability profiles of vortioxetine comparable to those seen in adults; hence, supporting the dose range of 5 to 20 mg/day. 16,25 Patients randomized to vortioxetine 10 mg received 5 mg/day for 2 days, and those randomized to vortioxetine 20 mg received 5 mg/day for 2 days followed by 10 mg/day and 15 mg/day for the next 2 days each before receiving the end dose. Patients in the fluoxetine arm received 10 mg/day for 6 days before the end dose of 20 mg/day.…”

Pharmacokinetics and Safety of Vortioxetine in Pediatric Patients

“…In addition, patients were asked to return all unused study medication. Patients who completed the main study period, if judged advisable by the investigator, were offered to continue in an optional, 6-month, open-label, flexible-dose extension trial (Findling et al 2016 ).…”

Vortioxetine Add-On to Methylphenidate for the Treatment of Symptoms of Sickness Behavior in Attention-Deficit Hyperactivity Disorder: Report of Two Cases

“…Consistently, a randomized, double-blind, placebo-controlled, proof-of-concept study performed in a group of ADHD patients aged 18-55 years old showed an overall reduction in the interference of ADHD symptoms with psychosocial functioning, alongside a reduced rate of adverse effects [10]. Although off-label, the efficacy and tolerability of VTX in children and adolescents with a depressive or anxiety disorder have been confirmed through a prospective open-label multinational multisite multidose trial, and its benefits as an addon therapy to MPH have already been investigated in a 15-year-old ADHD girl [11,12]. Interestingly, another antidepressant, the selective norepinephrine reuptake inhibitor (NRI) viloxazine, has been recently approved in the USA for the treatment of ADHD in pediatric patients aged 6-17 years [13].…”