Systematic review of management for treatment-resistant depression in adolescents

Background: Current guidelines for treatment-resistant depression in adolescents remain inadequate. This study aimed to systematically review the management of treatment-resistant depression in adolescent patients. Methods: We conducted an electronic database search of PUBMED, EMBASE, Cochrane, Web of Science and PsycINFO for studies with adolescent treatment-resistant depression published up to January 2014. Treatment-resistant depression was defined as failure to respond to at least one course of psychological or pharmacological treatment for depression with an adequate dosage, duration, and appropriate compliance during the current illness episode. The Cochrane risk-of-bias method was used to assess the quality of randomized controlled trials. A meta-analysis of all active treatments was conducted. Results: Eight studies with 411 depressed adolescents that fit predetermined criteria investigated pharmacological treatments and psychotherapies. Six were open-label studies, and two were randomized controlled trials. The overall response rate for all active treatments investigated was 46% (95% CI 33 to 59; N = 411) with a moderately high degree of heterogeneity (I2 = 76.1%, 95% CI = 47%-86%). When only the two randomized trials were included, the overall response rate of active treatment was 53% (95% CI = 38-67; N = 347). In these randomized trials, SSRI therapy plus CBT was significantly more effective than SSRI therapy alone, while amitriptyline was not more effective than placebo. Conclusions: Approximately half of the adolescents who presented with treatment-refractory depression responded to active treatment, which suggests that practitioners should remain persistent in managing these challenging cases. The combination of antidepressant medication and psychotherapy should be recommended for adolescents who present with treatment-resistant depression.