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Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder
Objectives: To evaluate the short-term efficacy and safety of desvenlafaxine (25–50 mg/d) compared with placebo in children and adolescents with major depressive disorder (MDD). Methods: Outpatient children (7–11 years) and adolescents (12–17 years) who met DSM-IV-TR criteria for MDD and had screeni...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Mary Ann Liebert, Inc.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771543/ https://www.ncbi.nlm.nih.gov/pubmed/29189044 http://dx.doi.org/10.1089/cap.2017.0100 |
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author | Weihs, Karen L. Murphy, William Abbas, Richat Chiles, Deborah England, Richard D. Ramaker, Sara Wajsbrot, Dalia B. |
author_facet | Weihs, Karen L. Murphy, William Abbas, Richat Chiles, Deborah England, Richard D. Ramaker, Sara Wajsbrot, Dalia B. |
author_sort | Weihs, Karen L. |
collection | PubMed |
description | Objectives: To evaluate the short-term efficacy and safety of desvenlafaxine (25–50 mg/d) compared with placebo in children and adolescents with major depressive disorder (MDD). Methods: Outpatient children (7–11 years) and adolescents (12–17 years) who met DSM-IV-TR criteria for MDD and had screening and baseline Children's Depression Rating Scale–Revised (CDRS-R) total scores >40 were randomly assigned to 8-week treatment with placebo, desvenlafaxine (25, 35, or 50 mg/d based on baseline weight), or fluoxetine (20 mg/d). The primary efficacy endpoint was change from baseline in CDRS-R total score at week 8, analyzed using a mixed-effects model for repeated measures. Secondary efficacy endpoints included week 8 Clinical Global Impressions–Severity, Clinical Global Impressions–Improvement (CGI-I), and response (CGI-I ≤ 2). Safety assessments included adverse events, physical and vital sign measurements, laboratory evaluations, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. Results: The safety population included 339 patients (children, n = 130; adolescents, n = 209). The primary endpoint, change from baseline in CDRS-R total score at week 8, did not statistically separate from placebo, for either desvenlafaxine (adjusted mean [standard error] change, −22.6 [1.17]) or fluoxetine (−24.8 [1.17]; placebo, −23.1 [1.18]). Week 8 CGI-I response rates were significantly greater for fluoxetine (78.2%; p = 0.017) than for placebo (62.6%); desvenlafaxine (68.7%) did not differ from placebo. Other secondary outcomes were consistent with those obtained with CDRS-R. Rates of treatment-emergent adverse events were comparable among treatment groups (desvenlafaxine, 60.0%; placebo, 70.5%; and fluoxetine, 64.3%). Conclusion: Desvenlafaxine did not demonstrate efficacy for treating MDD in children and adolescents in this trial. Because neither desvenlafaxine nor the reference medication, fluoxetine, demonstrated a statistically significant difference from placebo on the primary endpoint, this was considered a failed trial and no efficacy conclusions can be drawn. Desvenlafaxine 25–50 mg/d was generally safe and well tolerated in children and adolescents in this study. |
format | Online Article Text |
id | pubmed-5771543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Mary Ann Liebert, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57715432018-02-01 Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder Weihs, Karen L. Murphy, William Abbas, Richat Chiles, Deborah England, Richard D. Ramaker, Sara Wajsbrot, Dalia B. J Child Adolesc Psychopharmacol Original Articles Objectives: To evaluate the short-term efficacy and safety of desvenlafaxine (25–50 mg/d) compared with placebo in children and adolescents with major depressive disorder (MDD). Methods: Outpatient children (7–11 years) and adolescents (12–17 years) who met DSM-IV-TR criteria for MDD and had screening and baseline Children's Depression Rating Scale–Revised (CDRS-R) total scores >40 were randomly assigned to 8-week treatment with placebo, desvenlafaxine (25, 35, or 50 mg/d based on baseline weight), or fluoxetine (20 mg/d). The primary efficacy endpoint was change from baseline in CDRS-R total score at week 8, analyzed using a mixed-effects model for repeated measures. Secondary efficacy endpoints included week 8 Clinical Global Impressions–Severity, Clinical Global Impressions–Improvement (CGI-I), and response (CGI-I ≤ 2). Safety assessments included adverse events, physical and vital sign measurements, laboratory evaluations, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. Results: The safety population included 339 patients (children, n = 130; adolescents, n = 209). The primary endpoint, change from baseline in CDRS-R total score at week 8, did not statistically separate from placebo, for either desvenlafaxine (adjusted mean [standard error] change, −22.6 [1.17]) or fluoxetine (−24.8 [1.17]; placebo, −23.1 [1.18]). Week 8 CGI-I response rates were significantly greater for fluoxetine (78.2%; p = 0.017) than for placebo (62.6%); desvenlafaxine (68.7%) did not differ from placebo. Other secondary outcomes were consistent with those obtained with CDRS-R. Rates of treatment-emergent adverse events were comparable among treatment groups (desvenlafaxine, 60.0%; placebo, 70.5%; and fluoxetine, 64.3%). Conclusion: Desvenlafaxine did not demonstrate efficacy for treating MDD in children and adolescents in this trial. Because neither desvenlafaxine nor the reference medication, fluoxetine, demonstrated a statistically significant difference from placebo on the primary endpoint, this was considered a failed trial and no efficacy conclusions can be drawn. Desvenlafaxine 25–50 mg/d was generally safe and well tolerated in children and adolescents in this study. Mary Ann Liebert, Inc. 2018-02-01 2018-02-01 /pmc/articles/PMC5771543/ /pubmed/29189044 http://dx.doi.org/10.1089/cap.2017.0100 Text en © Karen L. Weihs et al. 2017; Published by Mary Ann Liebert, Inc. This article is available under the Creative Commons License CC-BY-NC (http://creativecommons.org/licenses/by-nc/4.0). This license permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. Permission only needs to be obtained for commercial use and can be done via RightsLink. |
spellingShingle | Original Articles Weihs, Karen L. Murphy, William Abbas, Richat Chiles, Deborah England, Richard D. Ramaker, Sara Wajsbrot, Dalia B. Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder |
title | Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder |
title_full | Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder |
title_fullStr | Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder |
title_full_unstemmed | Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder |
title_short | Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder |
title_sort | desvenlafaxine versus placebo in a fluoxetine-referenced study of children and adolescents with major depressive disorder |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771543/ https://www.ncbi.nlm.nih.gov/pubmed/29189044 http://dx.doi.org/10.1089/cap.2017.0100 |
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