According to results of a randomized controlled trial, youth patients with major depressive disorder who exhibited greater improvement in depressive symptoms following 3 months of treatment had a significantly lower risk of relapse compared to patients with continued depressive symptoms.

In order to assess predictors and moderators associated with relapse, the study authors conducted a literature review to identify youth patients with major depressive disorder. A total of 102 patients aged 7 to 18 years who responded to 12 weeks of fluoxetine therapy (acute phase) were included in the analysis. During the continuation treatment phase, patients were randomly assigned to receive either fluoxetine or placebo.

The study authors explained, “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 total score of ≥40 according to the Children’s Depression Rating Scale-Revised in addition to worsening of depressive symptoms for ≥2 weeks. 

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Results of the study determined that youth patients with baseline comorbid dysthymia and “low levels of family leadership” had an increased risk of relapse compared to their counterparts (adjusted odds ratio [OR]: 2.88; P=0.03 and adjusted OR: 1.39; P=0.006, respectively). Additionally, the risk of relapse was increased in patients with higher levels of depression (OR: 1.21; P=0.003), insomnia (OR: 6.74; P=0.006), and irritability (OR: 7.40; P=0.01) at the end of 12 weeks of treatment.

The study authors also reported that an increased risk of relapse was observed in patients with higher baseline levels of depressive symptoms taking fluoxetine for continuation treatment (adjusted OR: 1.14; p=0.03). Additionally, the risk of relapse was significantly higher in female patients taking fluoxetine for continuation treatment compared to males (adjusted OR: 8.86; p=0.007).

The study authors concluded, “Youth with greater improvement by the end of 3 months of treatment were less likely to relapse than those with continued depressive symptoms.” They added, “Targeting residual symptoms, particularly sleep disturbance and irritability, earlier in treatment may reduce relapse rates.”


Kennard, B.D. et al. Predictors and moderators of relapse in children and adolescents with major depressive disorder. J. Clinical Psychiatry 2018;79(2):15m10330.