Predictors and Moderators of Relapse in Children and Adolescents With Major Depressive Disorder

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