Dropout Prevalence and Associated Factors in Randomized Clinical Trials of Adolescents Treated for Depression: Systematic Review and Meta-analysis

Purpose: Depression currently affects 350 million people, and its prevalence among adolescents is 4% to 8%. Adolescents who abandon antidepressant treatment or drop out of clinical trials are less likely to recover or experience a remission of symptoms because they are not being followed up by a medical team. The objective of this study was to analyze the dropout rates of randomized clinical trials of depressed adolescents receiving treatment with antidepressant drugs and the factors associated with nonadherence by summarizing this information in a systematic review and meta-analysis.

Methods: Articles were retrieved from MEDLINE, EMBASE, Cochrane, Clinical Trial, PsycINFO, and Web of Science using the MeSH terms "depressive disorder," "randomized trials," and "adolescents." The evaluation of study quality was performed by using the Cochrane Handbook for Systematic Reviews of Interventions and the Jadad scale.

Findings: The final sample included 50 articles, of which 44 presented dropout rates. The overall dropout prevalence was 23% (95% CI, 20-27; P < 0.0001). Participants aged ≥16 years, those treated with serotonin norepinephrine reuptake inhibitors, and those receiving medication only exhibited the highest dropout prevalence, respectively (33% [95% CI, 27-39], 45% [95% CI, 31-64], and 15% [95% CI, 13-17]). The adverse effects most associated with dropout were attempted suicide followed by mania, skin rash, and headache. Problems relating to clinical trials and family arbitration were also related with dropout.

Implications: Serotonin/norepinephrine reuptake inhibitor treatment, adolescent age >16 years, and receiving medication were the only factors demonstrating a higher association with dropout rates. Selective serotonin reuptake inhibitors were linked to the lowest prevalence, probably due to fewer perceived problems with related adverse effects and higher efficacy in adolescents. Cognitive-behavioral therapy combined with pharmacotherapy produced a lower nonadherence prevalence; this approach can be an alternative to avoid dropouts and relapse. Prospero identifier: CRD42014013475.