Treatment-Resistant Depression in Adolescents: A Comprehensive Review

Major depressive disorder in youth is associated with significant mortality by suicide [1], protracted course of illness [2], high risk of recurrence [3], significant nonresponse to treatment [4,5], progression to bipolar disorder within 5 years [6-8], and high frequency of affective illness in family members [9]. Even with the gold standard treatment with an SSRI and concurrent cognitive behavioral therapy, 30% to 40% will not respond to treatment, thus classified as “treatment-resistant” [5,10,11]. A meta-analysis of published, randomized, placebocontrolled trials of SSRIs in depressed youth revealed an effect size of only 0.26 [12]. This further illustrates the poor response of SSRIs in youth depression. Treatment-resistant depression is associated with poor prognosis and high risk for suicide, indicating the need for more aggressive and clinically effective treatment than SSRIs alone can provide.