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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.

Background: Major depressive disorder (MDD) is a debilitating and costly mental disorder. Although commercially available antidepressants have proliferated over the last 20 years, a substantial number of patients either do not respond adequately to these drugs or are unable to tolerate their adverse effects. One common approach has been to augment conventional antidepressants with an adjunctive agent, but the optimal selection of atypical antipsychotic agents for adjunctive treatment of treatment-resistant depression (TRD) remains controversial., Methods/design: An electronic literature search of PubMed, the Cochrane Library, Embase, Web of Science, LiLACS, CINAHL, and PsycINFO for studies will be conducted with no restrictions on language, publication year, or publication type. Several clinical trial registry agencies, pharmaceutical company websites, and FDA reports will also be reviewed. Randomized clinical trials (RCTs) with atypical antipsychotic augmentation treatment for treatment-resistant depression will be considered. Data will be independently extracted by two reviewers. Traditional pairwise meta-analyses will be performed for RCTs that directly compare different treatment arms. Then, Bayesian network meta-analyses will be performed to compare the relative efficacy and acceptability of different atypical antipsychotic agents (and doses). A sensitivity analysis will be performed by excluding studies classified as a small sample size, having a high placebo effect., Discussion: This systematic review and network meta-analysis will comparatively analyze the efficacy, quality of life, and acceptability profiles of atypical antipsychotic medications used for the adjunctive treatment of TRD. The findings should provide clinically relevant implications for comprehensively understanding the risk-benefit profiles of these adjunctive treatments., Systematic Review Registration: PROSPERO CRD 42014009666.