Predictors, Moderators, and Mediators Associated With Treatment Outcome in Randomized Clinical Trials Among Adolescents With Depression

Abstract

IMPORTANCEThe 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). OBJECTIVE To describe predictors, moderators, and mediators associated with outcomes in RCTs for the treatment of depressive disorders in adolescents. EVIDENCE REVIEWA 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.FINDINGS 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. CONCLUSIONS AND RELEVANCEThis 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.

Predictors of outcome after a time-limited psychosocial intervention for adolescent depression

“…Our finding that male gender was a predictor of both remission and of larger decrease in depressive symptoms was unexpected. Previous research suggests that female, rather than male, gender might be a predictor of better outcome ( Weisz et al, 1995 ; Bolton et al, 2007 ); or that gender has no effect on outcome ( Clarke et al, 1992 ; Curry et al, 2006 ; Weisz et al, 2006 ; Courtney et al, 2022 ) of treatment for adolescent depression. Our finding may, however, also be related to females having higher depressive symptom scores at baseline.…”

“…Most meta-analyses of adolescent depression trials have not found gender to have an effect on treatment outcome ( Clarke et al, 1992 ; Curry et al, 2006 ; Weisz et al, 2006 ; Courtney et al, 2022 ). However, in an early meta-analysis, Weisz et al (1995) reported adolescent girls to benefit more from psychotherapy than boys, while among prepubertal children the gender effect was not found.…”

“…However, in an early meta-analysis, Weisz et al (1995) reported adolescent girls to benefit more from psychotherapy than boys, while among prepubertal children the gender effect was not found. The scoping review by Courtney et al (2022) suggests that socioeconomic status is not a powerful predictor of outcome in adolescent depression.…”

Development, Reach, Acceptability and Associated Clinical Changes of a Group Intervention to Improve Caregiver-Adolescent Relationships in the Context of Adolescent Depression

“…Second, maladaptive affective responding (how caregivers respond to adolescent's negative and positive affect, such as ignoring, minimizing, supporting or validating; Katz & Hunter, 2007) is associated with higher levels of adolescent depression (Katz et al, 2014;Shortt et al, 2016;Yap, Allen, & Ladouceur, 2008) and predicts the development of depression in prospective longitudinal samples (Nelis, Bastin, Raes, & Bijttebier, 2019;Schwartz et al, 2014). Third, caregiver-adolescent conflict is associated with more adolescent depression symptoms crosssectionally and over time (Sheeber, Davis, Leve, Hops, & Tildesley, 2007;Sheeber, Hops, Alpert, Davis, & Andrews, 1997;Weymouth, Buehler, Zhou, & Henson, 2016) and predicts poorer response to evidence-based treatment for adolescent depression (Courtney et al, 2022).…”

“…Secondary analyses of clinical trials suggest that caregiver-adolescent relationship problems may be a significant factor that limits adolescent response to evidence-based treatments for depression (e.g., Birmaher et al, 2000;Brent et al, 2009;Gunlicks-Stoessel, Mufson, Jekal, & Turner, 2010;Wilkinson, Kelvin, Roberts, Dubicka, & Goodyer, 2011). A recent review of clinical trials for adolescent depression found that of 53 predictor and moderator variables tested, parent-child conflict was among the variables most consistently associated with less favorable outcomes (Courtney et al, 2022).…”