An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression

Apurva Prakash, Evelyn Lobo, Christopher J Kratochvil, Roy N. Tamura, Beth A. Pangallo, Kristin E. Bullok, Tonya Quinlan, Graham J. Emslie, John S. March

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective: This preliminary, 32-week study assessed the safety, tolerability, and pharmacokinetics of duloxetine in pediatric patients (aged 7-17 years) with major depressive disorder. Methods: Patients received flexible duloxetine doses of 20-120-mg once daily, with dose changes made based on clinical improvement and tolerability. Pharmacokinetic samples were collected across all duloxetine doses, and data were analyzed using population modeling. Primary outcome measures included treatment-emergent adverse events (TEAEs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Of the 72 enrolled patients, 48 (66.7%) completed acute treatment (18 weeks) and 42 (58.3%) completed extended treatment. Most patients (55/72; 76%) required doses ≥60-mg once daily to optimize efficacy based on investigator judgment and Clinical Global Impressions-Severity score. Body weight and age did not significantly affect duloxetine pharmacokinetic parameters. Typical duloxetine clearance in pediatric patients was ∼42%-60% higher than that in adults. Four patients (5.6%) discontinued due to TEAEs. Many (36/72, 50%) patients experienced potentially clinically significant (PCS) elevations in blood pressure, with most cases (21/36, 58%) being transient. As assessed via C-SSRS, one nonfatal suicidal attempt occurred, two patients (2.8%) experienced worsening of suicidal ideation, and among the 19 patients reporting suicidal ideation at baseline, 17 (90%) reported improvement in suicidal ideation. Conclusion: Results suggested that pediatric patients generally tolerated duloxetine doses of 30 to 120-mg once daily, although transient PCS elevations in blood pressure were observed in many patients. Pharmacokinetic results suggested that adjustment of total daily dose based on body weight or age is not warranted for pediatric patients and different total daily doses may not be warranted for pediatric patients relative to adults.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalJournal of Child and Adolescent Psychopharmacology
Volume22
Issue number1
DOIs
StatePublished - Feb 1 2012

Fingerprint

Pharmacokinetics
Depression
Pediatrics
Safety
Suicidal Ideation
Duloxetine Hydrochloride
Suicide
Body Weight
Blood Pressure
Social Adjustment
Vital Signs
Major Depressive Disorder
Therapeutics
Research Personnel
Outcome Assessment (Health Care)

ASJC Scopus subject areas

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

Cite this

An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression. / Prakash, Apurva; Lobo, Evelyn; Kratochvil, Christopher J; Tamura, Roy N.; Pangallo, Beth A.; Bullok, Kristin E.; Quinlan, Tonya; Emslie, Graham J.; March, John S.

In: Journal of Child and Adolescent Psychopharmacology, Vol. 22, No. 1, 01.02.2012, p. 48-55.

Research output: Contribution to journalArticle

Prakash, Apurva ; Lobo, Evelyn ; Kratochvil, Christopher J ; Tamura, Roy N. ; Pangallo, Beth A. ; Bullok, Kristin E. ; Quinlan, Tonya ; Emslie, Graham J. ; March, John S. / An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression. In: Journal of Child and Adolescent Psychopharmacology. 2012 ; Vol. 22, No. 1. pp. 48-55.
@article{e8dd17a0e94947b1a1d37fa1775670cf,
title = "An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression",
abstract = "Objective: This preliminary, 32-week study assessed the safety, tolerability, and pharmacokinetics of duloxetine in pediatric patients (aged 7-17 years) with major depressive disorder. Methods: Patients received flexible duloxetine doses of 20-120-mg once daily, with dose changes made based on clinical improvement and tolerability. Pharmacokinetic samples were collected across all duloxetine doses, and data were analyzed using population modeling. Primary outcome measures included treatment-emergent adverse events (TEAEs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Of the 72 enrolled patients, 48 (66.7{\%}) completed acute treatment (18 weeks) and 42 (58.3{\%}) completed extended treatment. Most patients (55/72; 76{\%}) required doses ≥60-mg once daily to optimize efficacy based on investigator judgment and Clinical Global Impressions-Severity score. Body weight and age did not significantly affect duloxetine pharmacokinetic parameters. Typical duloxetine clearance in pediatric patients was ∼42{\%}-60{\%} higher than that in adults. Four patients (5.6{\%}) discontinued due to TEAEs. Many (36/72, 50{\%}) patients experienced potentially clinically significant (PCS) elevations in blood pressure, with most cases (21/36, 58{\%}) being transient. As assessed via C-SSRS, one nonfatal suicidal attempt occurred, two patients (2.8{\%}) experienced worsening of suicidal ideation, and among the 19 patients reporting suicidal ideation at baseline, 17 (90{\%}) reported improvement in suicidal ideation. Conclusion: Results suggested that pediatric patients generally tolerated duloxetine doses of 30 to 120-mg once daily, although transient PCS elevations in blood pressure were observed in many patients. Pharmacokinetic results suggested that adjustment of total daily dose based on body weight or age is not warranted for pediatric patients and different total daily doses may not be warranted for pediatric patients relative to adults.",
author = "Apurva Prakash and Evelyn Lobo and Kratochvil, {Christopher J} and Tamura, {Roy N.} and Pangallo, {Beth A.} and Bullok, {Kristin E.} and Tonya Quinlan and Emslie, {Graham J.} and March, {John S.}",
year = "2012",
month = "2",
day = "1",
doi = "10.1089/cap.2011.0072",
language = "English (US)",
volume = "22",
pages = "48--55",
journal = "Journal of Child and Adolescent Psychopharmacology",
issn = "1044-5463",
publisher = "Mary Ann Liebert Inc.",
number = "1",

}

TY - JOUR

T1 - An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression

AU - Prakash, Apurva

AU - Lobo, Evelyn

AU - Kratochvil, Christopher J

AU - Tamura, Roy N.

AU - Pangallo, Beth A.

AU - Bullok, Kristin E.

AU - Quinlan, Tonya

AU - Emslie, Graham J.

AU - March, John S.

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Objective: This preliminary, 32-week study assessed the safety, tolerability, and pharmacokinetics of duloxetine in pediatric patients (aged 7-17 years) with major depressive disorder. Methods: Patients received flexible duloxetine doses of 20-120-mg once daily, with dose changes made based on clinical improvement and tolerability. Pharmacokinetic samples were collected across all duloxetine doses, and data were analyzed using population modeling. Primary outcome measures included treatment-emergent adverse events (TEAEs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Of the 72 enrolled patients, 48 (66.7%) completed acute treatment (18 weeks) and 42 (58.3%) completed extended treatment. Most patients (55/72; 76%) required doses ≥60-mg once daily to optimize efficacy based on investigator judgment and Clinical Global Impressions-Severity score. Body weight and age did not significantly affect duloxetine pharmacokinetic parameters. Typical duloxetine clearance in pediatric patients was ∼42%-60% higher than that in adults. Four patients (5.6%) discontinued due to TEAEs. Many (36/72, 50%) patients experienced potentially clinically significant (PCS) elevations in blood pressure, with most cases (21/36, 58%) being transient. As assessed via C-SSRS, one nonfatal suicidal attempt occurred, two patients (2.8%) experienced worsening of suicidal ideation, and among the 19 patients reporting suicidal ideation at baseline, 17 (90%) reported improvement in suicidal ideation. Conclusion: Results suggested that pediatric patients generally tolerated duloxetine doses of 30 to 120-mg once daily, although transient PCS elevations in blood pressure were observed in many patients. Pharmacokinetic results suggested that adjustment of total daily dose based on body weight or age is not warranted for pediatric patients and different total daily doses may not be warranted for pediatric patients relative to adults.

AB - Objective: This preliminary, 32-week study assessed the safety, tolerability, and pharmacokinetics of duloxetine in pediatric patients (aged 7-17 years) with major depressive disorder. Methods: Patients received flexible duloxetine doses of 20-120-mg once daily, with dose changes made based on clinical improvement and tolerability. Pharmacokinetic samples were collected across all duloxetine doses, and data were analyzed using population modeling. Primary outcome measures included treatment-emergent adverse events (TEAEs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Of the 72 enrolled patients, 48 (66.7%) completed acute treatment (18 weeks) and 42 (58.3%) completed extended treatment. Most patients (55/72; 76%) required doses ≥60-mg once daily to optimize efficacy based on investigator judgment and Clinical Global Impressions-Severity score. Body weight and age did not significantly affect duloxetine pharmacokinetic parameters. Typical duloxetine clearance in pediatric patients was ∼42%-60% higher than that in adults. Four patients (5.6%) discontinued due to TEAEs. Many (36/72, 50%) patients experienced potentially clinically significant (PCS) elevations in blood pressure, with most cases (21/36, 58%) being transient. As assessed via C-SSRS, one nonfatal suicidal attempt occurred, two patients (2.8%) experienced worsening of suicidal ideation, and among the 19 patients reporting suicidal ideation at baseline, 17 (90%) reported improvement in suicidal ideation. Conclusion: Results suggested that pediatric patients generally tolerated duloxetine doses of 30 to 120-mg once daily, although transient PCS elevations in blood pressure were observed in many patients. Pharmacokinetic results suggested that adjustment of total daily dose based on body weight or age is not warranted for pediatric patients and different total daily doses may not be warranted for pediatric patients relative to adults.

UR - http://www.scopus.com/inward/record.url?scp=84857334131&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857334131&partnerID=8YFLogxK

U2 - 10.1089/cap.2011.0072

DO - 10.1089/cap.2011.0072

M3 - Article

C2 - 22251023

AN - SCOPUS:84857334131

VL - 22

SP - 48

EP - 55

JO - Journal of Child and Adolescent Psychopharmacology

JF - Journal of Child and Adolescent Psychopharmacology

SN - 1044-5463

IS - 1

ER -