Pharmacokinetics and Safety of Vortioxetine in Pediatric Patients

Robert L Findling, Adelaide S. Robb, Melissa DelBello, Michael Huss, Nora McNamara, Elias Sarkis, Russell Scheffer, Lis H. Poulsen, Grace Chen, Ole Michael Lemming, Johan Areberg, Philippe Auby

Research output: Contribution to journalArticle

Abstract

Objective: The primary objectives of this study were to evaluate the pharmacokinetics (PK) and tolerability of single and multiple doses of vortioxetine in children and adolescents with a depressive or anxiety disorder and to provide supportive information for appropriate dosing regimens for pediatric clinical trials. Methods: This prospective, open-label, multinational, multisite, multiple-dose trial enrolled 48 patients (children and adolescents; 1:1 ratio) divided into 8 cohorts (4 adolescent and 4 child), with each cohort including 6 patients. The cohorts in each age group were assigned to receive one of four dosing regimens: vortioxetine 5, 10, 15, or 20 mg q.d. for 14 days. The total treatment period lasted 14-20 days with patients in the higher dose cohorts uptitrated over 2-6 days. Plasma samples for PK analysis were obtained on the first and last days of dosing. Results: Among children and adolescents, respectively, 62% and 92% had depression and 58% and 33% had anxiety disorder. Comorbid attention-deficit/hyperactivity disorder (ADHD) was present in 50% of children and 38% of adolescents. After 14 days q.d. at the target dose, the PK of vortioxetine concentrations was generally proportional to the dose in both age groups. Exposure, as assessed by maximum plasma concentrations and area under the plasma concentration-time curve from time 0 to 24 hours, was 30%-40% lower in adolescents than in children. There was no significant relationship between sex, height, or ADHD diagnosis and PK parameters. Most adverse events were mild in severity and consistent with those seen in adults. Conclusion: The results suggest that the dosages of vortioxetine evaluated (5-20 mg q.d.; approved for treatment in adults) and the uptitration schedule used are appropriate for pediatric efficacy and safety trials.

Original languageEnglish (US)
Pages (from-to)526-534
Number of pages9
JournalJournal of Child and Adolescent Psychopharmacology
Volume27
Issue number6
DOIs
StatePublished - Aug 1 2017

Fingerprint

Pharmacokinetics
Pediatrics
Safety
Attention Deficit Disorder with Hyperactivity
Anxiety Disorders
Age Groups
Depressive Disorder
vortioxetine
Appointments and Schedules
Clinical Trials
Depression
Therapeutics

Keywords

  • adolescents
  • adverse events
  • antidepressant
  • children
  • dosing
  • pharmacokinetics
  • vortioxetine

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Pharmacokinetics and Safety of Vortioxetine in Pediatric Patients. / Findling, Robert L; Robb, Adelaide S.; DelBello, Melissa; Huss, Michael; McNamara, Nora; Sarkis, Elias; Scheffer, Russell; Poulsen, Lis H.; Chen, Grace; Lemming, Ole Michael; Areberg, Johan; Auby, Philippe.

In: Journal of Child and Adolescent Psychopharmacology, Vol. 27, No. 6, 01.08.2017, p. 526-534.

Research output: Contribution to journalArticle

Findling, RL, Robb, AS, DelBello, M, Huss, M, McNamara, N, Sarkis, E, Scheffer, R, Poulsen, LH, Chen, G, Lemming, OM, Areberg, J & Auby, P 2017, 'Pharmacokinetics and Safety of Vortioxetine in Pediatric Patients', Journal of Child and Adolescent Psychopharmacology, vol. 27, no. 6, pp. 526-534. https://doi.org/10.1089/cap.2016.0155
Findling, Robert L ; Robb, Adelaide S. ; DelBello, Melissa ; Huss, Michael ; McNamara, Nora ; Sarkis, Elias ; Scheffer, Russell ; Poulsen, Lis H. ; Chen, Grace ; Lemming, Ole Michael ; Areberg, Johan ; Auby, Philippe. / Pharmacokinetics and Safety of Vortioxetine in Pediatric Patients. In: Journal of Child and Adolescent Psychopharmacology. 2017 ; Vol. 27, No. 6. pp. 526-534.
@article{a48948c76ce94102be4d513d0a01770f,
title = "Pharmacokinetics and Safety of Vortioxetine in Pediatric Patients",
abstract = "Objective: The primary objectives of this study were to evaluate the pharmacokinetics (PK) and tolerability of single and multiple doses of vortioxetine in children and adolescents with a depressive or anxiety disorder and to provide supportive information for appropriate dosing regimens for pediatric clinical trials. Methods: This prospective, open-label, multinational, multisite, multiple-dose trial enrolled 48 patients (children and adolescents; 1:1 ratio) divided into 8 cohorts (4 adolescent and 4 child), with each cohort including 6 patients. The cohorts in each age group were assigned to receive one of four dosing regimens: vortioxetine 5, 10, 15, or 20 mg q.d. for 14 days. The total treatment period lasted 14-20 days with patients in the higher dose cohorts uptitrated over 2-6 days. Plasma samples for PK analysis were obtained on the first and last days of dosing. Results: Among children and adolescents, respectively, 62{\%} and 92{\%} had depression and 58{\%} and 33{\%} had anxiety disorder. Comorbid attention-deficit/hyperactivity disorder (ADHD) was present in 50{\%} of children and 38{\%} of adolescents. After 14 days q.d. at the target dose, the PK of vortioxetine concentrations was generally proportional to the dose in both age groups. Exposure, as assessed by maximum plasma concentrations and area under the plasma concentration-time curve from time 0 to 24 hours, was 30{\%}-40{\%} lower in adolescents than in children. There was no significant relationship between sex, height, or ADHD diagnosis and PK parameters. Most adverse events were mild in severity and consistent with those seen in adults. Conclusion: The results suggest that the dosages of vortioxetine evaluated (5-20 mg q.d.; approved for treatment in adults) and the uptitration schedule used are appropriate for pediatric efficacy and safety trials.",
keywords = "adolescents, adverse events, antidepressant, children, dosing, pharmacokinetics, vortioxetine",
author = "Findling, {Robert L} and Robb, {Adelaide S.} and Melissa DelBello and Michael Huss and Nora McNamara and Elias Sarkis and Russell Scheffer and Poulsen, {Lis H.} and Grace Chen and Lemming, {Ole Michael} and Johan Areberg and Philippe Auby",
year = "2017",
month = "8",
day = "1",
doi = "10.1089/cap.2016.0155",
language = "English (US)",
volume = "27",
pages = "526--534",
journal = "Journal of Child and Adolescent Psychopharmacology",
issn = "1044-5463",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

TY - JOUR

T1 - Pharmacokinetics and Safety of Vortioxetine in Pediatric Patients

AU - Findling, Robert L

AU - Robb, Adelaide S.

AU - DelBello, Melissa

AU - Huss, Michael

AU - McNamara, Nora

AU - Sarkis, Elias

AU - Scheffer, Russell

AU - Poulsen, Lis H.

AU - Chen, Grace

AU - Lemming, Ole Michael

AU - Areberg, Johan

AU - Auby, Philippe

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Objective: The primary objectives of this study were to evaluate the pharmacokinetics (PK) and tolerability of single and multiple doses of vortioxetine in children and adolescents with a depressive or anxiety disorder and to provide supportive information for appropriate dosing regimens for pediatric clinical trials. Methods: This prospective, open-label, multinational, multisite, multiple-dose trial enrolled 48 patients (children and adolescents; 1:1 ratio) divided into 8 cohorts (4 adolescent and 4 child), with each cohort including 6 patients. The cohorts in each age group were assigned to receive one of four dosing regimens: vortioxetine 5, 10, 15, or 20 mg q.d. for 14 days. The total treatment period lasted 14-20 days with patients in the higher dose cohorts uptitrated over 2-6 days. Plasma samples for PK analysis were obtained on the first and last days of dosing. Results: Among children and adolescents, respectively, 62% and 92% had depression and 58% and 33% had anxiety disorder. Comorbid attention-deficit/hyperactivity disorder (ADHD) was present in 50% of children and 38% of adolescents. After 14 days q.d. at the target dose, the PK of vortioxetine concentrations was generally proportional to the dose in both age groups. Exposure, as assessed by maximum plasma concentrations and area under the plasma concentration-time curve from time 0 to 24 hours, was 30%-40% lower in adolescents than in children. There was no significant relationship between sex, height, or ADHD diagnosis and PK parameters. Most adverse events were mild in severity and consistent with those seen in adults. Conclusion: The results suggest that the dosages of vortioxetine evaluated (5-20 mg q.d.; approved for treatment in adults) and the uptitration schedule used are appropriate for pediatric efficacy and safety trials.

AB - Objective: The primary objectives of this study were to evaluate the pharmacokinetics (PK) and tolerability of single and multiple doses of vortioxetine in children and adolescents with a depressive or anxiety disorder and to provide supportive information for appropriate dosing regimens for pediatric clinical trials. Methods: This prospective, open-label, multinational, multisite, multiple-dose trial enrolled 48 patients (children and adolescents; 1:1 ratio) divided into 8 cohorts (4 adolescent and 4 child), with each cohort including 6 patients. The cohorts in each age group were assigned to receive one of four dosing regimens: vortioxetine 5, 10, 15, or 20 mg q.d. for 14 days. The total treatment period lasted 14-20 days with patients in the higher dose cohorts uptitrated over 2-6 days. Plasma samples for PK analysis were obtained on the first and last days of dosing. Results: Among children and adolescents, respectively, 62% and 92% had depression and 58% and 33% had anxiety disorder. Comorbid attention-deficit/hyperactivity disorder (ADHD) was present in 50% of children and 38% of adolescents. After 14 days q.d. at the target dose, the PK of vortioxetine concentrations was generally proportional to the dose in both age groups. Exposure, as assessed by maximum plasma concentrations and area under the plasma concentration-time curve from time 0 to 24 hours, was 30%-40% lower in adolescents than in children. There was no significant relationship between sex, height, or ADHD diagnosis and PK parameters. Most adverse events were mild in severity and consistent with those seen in adults. Conclusion: The results suggest that the dosages of vortioxetine evaluated (5-20 mg q.d.; approved for treatment in adults) and the uptitration schedule used are appropriate for pediatric efficacy and safety trials.

KW - adolescents

KW - adverse events

KW - antidepressant

KW - children

KW - dosing

KW - pharmacokinetics

KW - vortioxetine

UR - http://www.scopus.com/inward/record.url?scp=85027867353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027867353&partnerID=8YFLogxK

U2 - 10.1089/cap.2016.0155

DO - 10.1089/cap.2016.0155

M3 - Article

C2 - 28333546

AN - SCOPUS:85027867353

VL - 27

SP - 526

EP - 534

JO - Journal of Child and Adolescent Psychopharmacology

JF - Journal of Child and Adolescent Psychopharmacology

SN - 1044-5463

IS - 6

ER -