Double trouble: Do symptom severity and duration interact to predicting treatment outcomes in adolescent depression?

Abstract

Studies suggest that depression severity and duration interact to predict outcomes in depression treatment. To our knowledge, no study has explored this question in a sample with a placebo control, two therapies, and their combination nor with adolescents. We used data from the Treatment of Adolescent Depression Study (N = 439), in which adolescent were randomized to placebo (PBO), cognitive-behavioral therapy (CBT), antidepressants medications (MEDs), or their combination (COMB). We explore the interaction between depression severity, chronicity, and treatments (vs. placebo) in predicting outcomes. There was interaction between severity and chronicity when comparing COMB and CBT with PBO, but not MEDs. In non-chronic depression, the effects of CBT were inversely related to severity to the point that CBT appeared iatrogenic with more severe depression. In chronic depression, the effects of CBT did not vary by severity, but the relative effects of COMB grew, being smallest in milder, more dysthymic-like depression, and largest in chronic-severe depression. These findings support calls to classify depression by severity and chronicity as well efforts to risk stratify patients to different intensity of care according to these variables.

Keywords: Adolescents; Depression; Personalized medicine; Risk stratification; Stepped care.

Figure 1.. Estimated end of treatment (i.e., week 12) Reynolds Adolescent Depression Scale (RADS) for adolescents by baseline RADS severity for chronic and non-chronic depression

Note. Dark lines indicated predicted slope. Bands around the slope indicate 95% confidence intervals (CIs)

Figure 2.. Predicted effects of cognitive-behavioral therapy (CBT) and combination of CBT and fluoxetine, vs. placebo, by chronicity and severity

Note. Figure indicates the effects of treatment vs. placebo, by severity, in non-chronic and chronic depression. Y-axis plots predicted difference between treatment conditions and the placebo conditions. Lower scores are better and indicate greater differences in end of treatment depression scores on the Reynolds Adolescent Depression Scale (RADS), favoring the active treatments. Bands indicate 95% confidence interval. The horizontal line indicates an effect of 0. When CIs cross zero, it indicates the treatment is no different than placebo at that level of severity.