Antidepressant resistance in adolescents with major depressive disorder: A nationwide longitudinal study

Background: Studies have suggested that psychiatric comorbidities have major effects on antidepressant resistance in adult patients with major depressive disorder (MDD). However, the association between psychiatric comorbidities and antidepressant resistance remains unclear in adolescents with MDD. Methods: A total of 10,624 adolescents with MDD were selected from the Taiwan National Health Insurance Research Database between 2001 and 2010 and followed for one year. Treatment-resistant depression (TRD) was defined as unresponsiveness to a least two antidepressants, and treatment resistant tendency was defined as unresponsiveness to the first antidepressant. Psychiatric comorbidities, such as anxiety disorders, substance use disorders, and attention deficit hyperactivity disorder (ADHD), were assessed as confounding factors. Results: In our study, only 1.7% (n = 184) of adolescents with MDD met the TRD criteria but 23.3% (n = 2480) were classified as exhibiting treatment resistant tendency. Anxiety disorders (OR: 2.34, 95% CI: 1.73-3.16) and substance use disorders (OR: 2.41, 95% CI: 1.28-4.54) exhibited a correlation with TRD, and ADHD (OR: 1.34, 95% CI: 1.08-1.66) was associated with treatment resistant tendency. Conclusions: Approximately one-fourth of adolescents with MDD respond poorly to the first antidepressant treatment. The psychiatric comorbidities of anxiety disorders, substance use disorders, and ADHD may increase the risk of treatment resistance in adolescents with MDD.