Abstract
The application of precision medicine principles for the treatment of depressive disorders in adolescents requires an examination of the variables associated with depression outcomes in randomized clinical trials (RCTs). To describe predictors, moderators, and mediators associated with outcomes in RCTs for the treatment of depressive disorders in adolescents. A scoping review of RCTs for the treatment of depression in adolescents was conducted. Databases searched included MEDLINE, Embase, APA PsycInfo, and CINAHL. Included publications tested predictors, moderators, and/or mediators associated with depression symptom outcomes (eg, symptom reduction, response, remission) in RCTs pertaining to the treatment of adolescents, ages 13 to 17 years. Predictors were defined as variables that were associated with depression outcomes, independent of treatment group. Moderators were defined as baseline variables that were associated with differential outcomes between treatment groups. Mediators were defined by a formal mediation analysis. In duplicate, variables were extracted and coded with respect to analysis type (univariable or multivariable), statistical significance, direction of effect size, reporting of a priori hypotheses, and adjustment for multiple comparisons. Aggregated results were summarized by variable domain and RCT sample. Eighty-one articles reporting on variables associated with outcomes across 33 RCTs were identified, including studies of biological (10 RCTs), psychosocial (18 RCTs), and combined (4 RCTs) treatments as well as a service delivery model (1 RCT). Fifty-three variable domains were tested as baseline predictors of depression outcome, 41 as moderators, 19 as postbaseline predictors, and 5 as mediators. Variable domains that were reported as significant in at least 3 RCTs included age, sex/gender, baseline depression severity, early response to treatment, sleep changes, parent-child conflict, overall psychopathology, suicidal ideation, hopelessness, functional impairment, attendance at therapy sessions, and history of trauma. Two publications reported a priori hypotheses and adjustment for multiple comparisons, both finding that baseline depression severity and family conflict were associated with poorer outcomes. This review identified commonly researched variables requiring more scrutiny as well as underresearched variables to inform future study designs. Further efforts to discover predictors, moderators, and mediators associated with treatment response have great potential to optimize care for adolescents with depression.
Highlights
Depressive disorders in adolescents (DD-A) are prevalent,[1] impairing,[2,3] and associated with suicide.[4,5] In the United States, rates of depressive symptoms and suicide in adolescents have increased over the past 10 to 15 years.[6,7] Current treatment approaches have limited benefit.[8,9] The application of precision medicine hopes to improve outcomes by offering “treatment strategies that take individual variability into account.”[10]
Inclusion criteria were English-language randomized clinical trial (RCT) that assessed treatments of depressive disorders in adolescents in which (1) depression was defined as diagnoses of major depressive disorder, dysthymia/persistent depressive disorder, or depressive symptoms more severe than an established cutoff on a validated measure of depression symptom severity; (2) treatment interventions included biological interventions, psychosocial interventions, or service delivery models; (3) a test of any predictor, moderator, or mediator associated with depression outcomes was conducted
Of 98 RCTs identified in total in our search, 33 RCTs (Table 1; eTable 1 in Supplement 2)[28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60] reported results of at least 1 predictor, moderator, or mediator tested for association with depression outcome
Summary
Depressive disorders in adolescents (DD-A) are prevalent,[1] impairing,[2,3] and associated with suicide.[4,5] In the United States, rates of depressive symptoms and suicide in adolescents have increased over the past 10 to 15 years.[6,7] Current treatment approaches have limited benefit.[8,9] The application of precision medicine hopes to improve outcomes by offering “treatment strategies that take individual variability into account.”[10]. A good understanding of the variables associated with depression severity outcome in RCTs for the treatment of DD-A can indicate what works for whom and how.[12,13] Two previous evidence syntheses that have examined such variables[14,15] have included a very limited set of relevant studies
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