Treatment-Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance

To describe the clinical characteristics of adolescents with antidepressant treatment-resistant major depressive disorder (MDD) and to examine the utility of the Antidepressant Treatment Record (ATR) in categorizing treatment resistance in this population. Adolescents with treatment-resistant MDD enrolled in an interventional study underwent a baseline evaluation with the ATR, Children's Depression Rating Scale-Revised (CDRS-R), and Clinical Global Impressions-Severity (CGI-S) scales. Demographic and clinical characteristics were examined with regard to ATR-defined level of resistance (level 1 to ≥3) using analysis of variance and χ² tests. In adolescents with treatment-resistant MDD (N = 97), aged 12-21 years, most were female (65%), white (89%), and had recurrent illness (78%). Patients were severely ill (median CGI-S score of 5), had a mean CDRS-R score of 63 ± 10, and 17.5% had been hospitalized for depression-related symptoms. Fifty-two patients were classified as ATR 1, whereas 32 were classified as ATR level 2 and 13 patients as ≥3, respectively. For increasing ATR-defined levels, illness duration increased from 12.0 (range: 1.5-31.9) to 14.8 (range: 1.8-31.7) to 19.5 (range: 2.5-36.2) months and the likelihood of treatment with serotonin norepinephrine reuptake inhibitors (SNRIs) and dopamine norepinephrine reuptake inhibitors (DNRIs) similarly increased (p = 0.006 for both SNRIs and DNRIs) as did the likelihood of treatment with mixed dopamine serotonin receptor antagonists (χ² = 17, p < 0.001). This study underscores the morbidity and chronicity of treatment-resistant MDD in adolescents. The present characterization of related clinical features describes the use of nonselective serotonin reuptake inhibitors in adolescents with treatment-resistant depression and raises the possibility that those with the greatest medication treatment resistance are less likely to have had recurrent episodes. The study also demonstrates the utility of the ATR in categorizing treatment resistance in adolescents with MDD.