A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder

Sarah D. Atkinson, Apurva Prakash, Qi Zhang, Beth A. Pangallo, Mark E. Bangs, Graham J. Emslie, John S. March

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objective: The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). Methods: Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120mg once daily [QD], n=117), fluoxetine (20-40mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1%) duloxetine patients, 7 (6.8%) placebo patients, and 9 (8.0%) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79%) duloxetine, 19/19 (100%) placebo, and 16/19 (84%) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study. Conclusion: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901

Original languageEnglish (US)
Pages (from-to)180-189
Number of pages10
JournalJournal of Child and Adolescent Psychopharmacology
Volume24
Issue number4
DOIs
StatePublished - May 1 2014

Fingerprint

Major Depressive Disorder
Fluoxetine
Safety
Placebos
Suicidal Ideation
Depression
Suicide
Therapeutics
Duloxetine Hydrochloride
Investigational Drugs
Alanine Transaminase
Registries
Electrocardiography
Clinical Trials

ASJC Scopus subject areas

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

Cite this

A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. / Atkinson, Sarah D.; Prakash, Apurva; Zhang, Qi; Pangallo, Beth A.; Bangs, Mark E.; Emslie, Graham J.; March, John S.

In: Journal of Child and Adolescent Psychopharmacology, Vol. 24, No. 4, 01.05.2014, p. 180-189.

Research output: Contribution to journalArticle

Atkinson, Sarah D. ; Prakash, Apurva ; Zhang, Qi ; Pangallo, Beth A. ; Bangs, Mark E. ; Emslie, Graham J. ; March, John S. / A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. In: Journal of Child and Adolescent Psychopharmacology. 2014 ; Vol. 24, No. 4. pp. 180-189.
@article{336a8d9636204de381385af8d90d9c61,
title = "A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder",
abstract = "Objective: The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). Methods: Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120mg once daily [QD], n=117), fluoxetine (20-40mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1{\%}) duloxetine patients, 7 (6.8{\%}) placebo patients, and 9 (8.0{\%}) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79{\%}) duloxetine, 19/19 (100{\%}) placebo, and 16/19 (84{\%}) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study. Conclusion: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901",
author = "Atkinson, {Sarah D.} and Apurva Prakash and Qi Zhang and Pangallo, {Beth A.} and Bangs, {Mark E.} and Emslie, {Graham J.} and March, {John S.}",
year = "2014",
month = "5",
day = "1",
doi = "10.1089/cap.2013.0146",
language = "English (US)",
volume = "24",
pages = "180--189",
journal = "Journal of Child and Adolescent Psychopharmacology",
issn = "1044-5463",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder

AU - Atkinson, Sarah D.

AU - Prakash, Apurva

AU - Zhang, Qi

AU - Pangallo, Beth A.

AU - Bangs, Mark E.

AU - Emslie, Graham J.

AU - March, John S.

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Objective: The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). Methods: Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120mg once daily [QD], n=117), fluoxetine (20-40mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1%) duloxetine patients, 7 (6.8%) placebo patients, and 9 (8.0%) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79%) duloxetine, 19/19 (100%) placebo, and 16/19 (84%) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study. Conclusion: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901

AB - Objective: The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). Methods: Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120mg once daily [QD], n=117), fluoxetine (20-40mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1%) duloxetine patients, 7 (6.8%) placebo patients, and 9 (8.0%) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79%) duloxetine, 19/19 (100%) placebo, and 16/19 (84%) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study. Conclusion: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901

UR - http://www.scopus.com/inward/record.url?scp=84901254995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901254995&partnerID=8YFLogxK

U2 - 10.1089/cap.2013.0146

DO - 10.1089/cap.2013.0146

M3 - Article

C2 - 24813026

AN - SCOPUS:84901254995

VL - 24

SP - 180

EP - 189

JO - Journal of Child and Adolescent Psychopharmacology

JF - Journal of Child and Adolescent Psychopharmacology

SN - 1044-5463

IS - 4

ER -