Search

Objective: To identify predictors and moderators of relapse during continuation treatment among depressed youth randomly assigned to fluoxetine or placebo., Methods: Potential 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., Results: Youth 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)., Conclusions: This 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 Registration: ClinicalTrials.gov identifier: NCT00332787., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Objective: The Treatment for Adolescents With Depression Study (TADS) evaluates the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), and their combination in adolescents with major depressive disorder. The authors report effectiveness outcomes across a 1-year naturalistic follow-up period., Method: The randomized, controlled trial was conducted in 13 academic and community sites in the United States. Stages I, II, and III consisted of 12, 6, and 18 weeks of acute, consolidation, and continuation treatment, respectively. Following discontinuation of TADS treatments at the end of stage III, stage IV consisted of 1 year of naturalistic follow-up. The participants were 327 subjects between the ages of 12 and 17 with a primary DSM-IV diagnosis of major depressive disorder. No TADS treatment was provided during the follow-up period; treatment was available in the community. The primary dependent measures, rated by an independent evaluator blind to treatment status, were the total score on the Children's Depression Rating Scale-Revised and the rate of response, defined as a rating of much or very much improved on the Clinical Global Impressions improvement measure., Results: Sixty-six percent of the eligible subjects participated in at least one stage IV assessment. The benefits seen at the end of active treatment (week 36) persisted during follow-up on all measures of depression and suicidality., Conclusions: In contrast to earlier reports on short-term treatments, in which worsening after treatment is the rule, the longer treatment in the TADS was associated with persistent benefits over 1 year of naturalistic follow-up.

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.

Objective: Recent acute efficacy trials of antidepressants in youth have suggested that high placebo-response rates in children (< 12 years of age) indicate that children may be more responsive to non-specific treatment interventions. Yet, these studies generally have not presented age-specific outcome data. The objective of this study was to compare the efficacy outcomes for children (< 12 years of age) and adolescents (> or = 12 years of age) using the combined data from two previously published double-blind, placebo-controlled trials of fluoxetine., Methods: Children (< 12 years of age) and adolescents (> or = 12 years of age) with major depressive disorder were randomized to fluoxetine or placebo for 8-9 weeks of treatment. Outcome was assessed using the Children's Depression Rating Scale-Revised (CDRS-R) and Clinical Global Impressions scale., Results: Random regression of the CDRS-R showed a treatment group by age group interaction (F(1,338)=4.10, P=.044), indicating that the treatment effect was significantly more pronounced in children than adolescents. Within children, response at exit to fluoxetine was significantly better than placebo (56.9% vs 33.3%; P=.009). Adolescent response rates at exit were not significantly different between the groups (51.1% vs 38.6%; P=.128). Remission rates were low for both groups., Conclusion: In the combined fluoxetine trials, drug-placebo difference was greater in children compared with adolescents. Contrary to expectations, the placebo-response rate was lower in the children than the adolescents.