Fluoxetine Versus Placebo in Preventing Relapse of Major Depression in Children and Adolescents

Abstract

Objective-The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents.Method-After a detailed evaluation, children and adolescents 7-18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children's Depression Rating Scale-Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children's Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children's Depression Rating Scale.Results-Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group.Conclusions-Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.Major depressive disorder is a serious disorder in the pediatric age group, with 2%-8% of children and adolescents afflicted (1,2). Youths with depression often have significant impairment in relationships, school, and work and are at increased risk for substance abuse, attempted and completed suicide, and depression in adulthood (1,3,4). Furthermore, it appears that early-onset major depression may be a more chronic and recurrent disorder than depression that begins in adulthood (1,5). As many as 50%-75% of children with major depression have recurrent episodes (1,3). Recurrence most often occurs within 6-12 months after remission (6)(7)(8). Thus, depression is a serious disorder requiring early intervention. Treatment for major depression may be divided into three phases: acute, continuation, and maintenance treatment. Acute treatment refers to initial treatment designed to achieve response (a significant reduction in depressive symptoms) and ultimately remission (minimal or no symptoms). The goal of treatment is remission, although most randomized controlled trials include response as the primary aim. Continuation treatment follows acute treatment with the goal of preventing relapse of symptoms from the treated episode and consolidating symptom improvement for a longer duration (recovery). Continuation treatment generally lasts 4-9 mon...

Insomnia Moderates Outcome of Serotonin-Selective Reuptake Inhibitor Treatment in Depressed Youth

“…Similarly, in our 12 week open trial of fluoxetine, residual symptoms were common even among remitters, with poor school performance, sleep disturbance, and mood being the most common residual symptoms (Tao et al 2010). Teens with more symptoms remaining at the end of 12 weeks of treatment are less likely to be remitted at 18 and 36 weeks , and are more likely to relapse (Emslie et al 2008). Thus, identifying factors that are associated with slower response will allow us to potentially target those specific areas to speed response and ultimately lead to higher remission rates.…”

Childhood Depression Subscales Using Repeated Sessions on Children's Depression Rating Scale – Revised (CDRS-R) Scores

“…We examined two relapse prevention clinical trials in which youth with major depressive disorder (MDD) were treated openly with fluoxetine for the first 12 weeks (Emslie et al 2008;Kennard et al 2008). In one trial, 168 youth (ages 8-17 years) were treated with fluoxetine 10-40 mg for 12 weeks, and responders were eligible to enter into a double-blind discontinuation phase (Emslie et al 2008).…”

“…In one trial, 168 youth (ages 8-17 years) were treated with fluoxetine 10-40 mg for 12 weeks, and responders were eligible to enter into a double-blind discontinuation phase (Emslie et al 2008). In the other trial, 66 youth (ages 11-17 years) were treated with fluoxetine 10-40 mg for 12 weeks, and responders were randomized to either begin relapse prevention cognitive behavioral therapy (CBT) in addition to medication treatment, or to continue on fluoxetine alone (Kennard et al 2008). Patients in both studies were treated identically for the visits utilized in these analyses (first 12 weeks), and the data are reported by visit.…”

“…Patients in both studies were treated identically for the visits utilized in these analyses (first 12 weeks), and the data are reported by visit. Primary outcomes for both studies have been reported previously (Emslie et al 2008;Kennard et al 2008). …”

SMARTer Discontinuation Trial Designs for Developing an Adaptive Treatment Strategy

“…In the majority of discontinuation trials, the primary outcome is the time to first relapse in the postacute phase. For example, Emslie et al (2008) used a discontinuation trial to answer the following question: ''Among depressed children and adolescents who acutely respond to 12 weeks of fluoxetine, what is the effect of immediately discontinuing medication versus discontinuation after an additional 12 weeks of treatment on time to first relapse? '' Assessing the impact of different treatment durations is often the explicit and primary rationale for discontinuation trials.…”