Desvenlafaxine Versus Placebo in the Treatment of Children and Adolescents with Major Depressive Disorder

Abstract

Objective: To evaluate the short-term efficacy and safety of desvenlafaxine versus placebo in the treatment of 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 weeks of treatment with placebo, low exposure desvenlafaxine (20, 30, or 35 mg/day based on baseline weight), or higher exposure desvenlafaxine (25, 35, or 50 mg/day based on baseline weight). 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 assessments included Clinical Global Impressions-Severity and Clinical Global Impressions-Improvement scales. Safety assessments included adverse events and the Columbia-Suicide Severity Rating Scale.

Results: The safety population included 363 patients (children, n = 109; adolescents, n = 254). No statistical separation from placebo was observed for either desvenlafaxine group for CDRS-R total score or for any secondary efficacy endpoint. At week 8, adjusted mean (standard error) changes from baseline in CDRS-R total score for the desvenlafaxine low exposure, desvenlafaxine high exposure, and placebo groups were -23.7 (1.1), -24.4 (1.1), and -22.9 (1.1), respectively. The incidence of adverse events was similar among groups.

Conclusion: Low and high exposure desvenlafaxine groups did not demonstrate efficacy for the treatment of MDD in children and adolescents in this double-blind, placebo-controlled trial. Desvenlafaxine (20-50 mg/day) was generally safe and well tolerated with no new safety signals identified in pediatric patients with MDD in this study.

Trial registration: ClinicalTrials.gov NCT01371734.

Keywords: adolescents; children; clinical trial; desvenlafaxine; major depressive disorder; treatment efficacy.

FIG. 1.

Study flow and patient disposition ITT. ITT, intent-to-treat.

FIG. 2.

Adjusted mean (SE) change from baseline in CDRS-R score in children and adolescents; MMRM analysis, ITT population. *p = 0.013, desvenlafaxine low exposure versus placebo; p = 0.034, desvenlafaxine high exposure versus placebo. Adjusted mean difference vs placebo (95% CI), week 8: desvenlafaxine low exposure, 0.85 (−2.23, 3.94); desvenlafaxine high exposure, 1.52 (−1.56, 4.61). CDRS-R, Children's Depression Rating Scale-Revised; MMRM, mixed-effects model for repeated measures; SE, standard error.