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Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder.

ABSTRACT: 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.

SUBMITTER: Weihs KL

PROVIDER: S-EPMC5771543 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder.

Weihs Karen L KL Murphy William W Abbas Richat R Chiles Deborah D England Richard D RD Ramaker Sara S Wajsbrot Dalia B DB

Journal of child and adolescent psychopharmacology 20171130 1

<h4>Objectives</h4>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).<h4>Methods</h4>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 b ...[more]

PMID: 29189044

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Project description:BackgroundEsketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission.MethodsPost hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined.ResultsThe median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up.ConclusionTreatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality.Trial registrationClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017).

Project description:ObjectiveTo identify predictors and moderators of relapse during continuation treatment among depressed youth randomly assigned to fluoxetine or placebo.MethodsPotential predictors and moderators of relapse that were identified by a literature review were examined in 102 youth (aged 7-18 years), diagnosed with major depressive disorder as defined by DSM-IV criteria, who were considered responders after 12 weeks of fluoxetine treatment (acute phase). This randomized controlled trial was conducted from June 2000 through October 2005. Each candidate predictor and moderator was evaluated with a multiple logistic regression model to examine the main and interaction effects of 12 weeks of continuation treatment on relapse status (at week 24) while controlling for age, sex, and depression severity. Relapse was defined as a Children's Depression Rating Scale-Revised total score ≥ 40 with worsening of depressive symptoms for at least 2 weeks.ResultsYouth with comorbid dysthymia (adjusted odds ratio [OR] = 2.88, P = .03) and low levels of family leadership (adjusted OR = 1.39, P = .006) at baseline are more likely to relapse than their counterparts. Higher levels of depression (OR = 1.21, P = .003) and higher levels of residual sleep disturbance (insomnia) (OR = 6.74, P = .006) and irritability (OR = 7.40, P = .01) at the end of acute treatment (12 weeks) increased the odds of relapse. Higher levels of depressive symptoms at baseline in youth who remained on fluoxetine for continuation treatment were associated with increased odds of relapse (adjusted OR = 1.14, P = .03). Females who remained on fluoxetine for the duration of continuation treatment were almost 9 times more likely to relapse than males (adjusted OR = 8.86, P = .007).ConclusionsThis is the first large continuation study for treatment of depression in youth to examine predictors and moderators of relapse. Youth with greater improvement by the end of 3 months of treatment were less likely to relapse than those with continued depressive symptoms. In addition, youth with comorbid dysthymia had 3 times greater risk of relapse that those without. Targeting residual symptoms, particularly sleep disturbance and irritability, earlier in treatment may reduce relapse rates.Trial registrationClinicalTrials.gov identifier: NCT00332787.

Dataset Information

Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder.

Publications

Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder.

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