Predictors, Moderators, and Mediators Associated With Treatment Outcome in Randomized Clinical Trials Among Adolescents With Depression: A Scoping Review.

Importance: 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). Objective: To describe predictors, moderators, and mediators associated with outcomes in RCTs for the treatment of depressive disorders in adolescents. Evidence Review: 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. 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 Relevance: 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.

Eating, sleeping and moving recommendations in clinical practice guidelines for paediatric depression: umbrella review.

BACKGROUND: Current first-line treatments for paediatric depression demonstrate mild-to-moderate effectiveness. This has spurred a growing body of literature on lifestyle recommendations pertaining to nutrition, sleep and exercise for treating paediatric depression. AIMS: Paediatric depression clinical practice guidelines (CPGs) were reviewed for quality and to catalogue recommendations on nutrition, sleep and exercise made by higher-quality CPGs. METHOD: Searches were conducted in Medline, EMBASE, PsycINFO, Web of Science and CINAHL, and grey literature CPGs databases for relevant CPGs. Eligible CPGs with a minimum or high-quality level, as determined by the Appraisal of Guidelines for Research and Evaluation, Second Edition instrument, were included if they were (a) paediatric; (b) CPGs, practice parameter or consensus or expert committee recommendations; (c) for depression; (d) the latest version and (e) lifestyle recommendations for nutrition, sleep or exercise. Key information extracted included author(s), language, year of publication, country, the institutional body issuing the CPG, target disorder, age group, lifestyle recommendation and the methods used to determine CPG lifestyle recommendations. RESULTS: Ten paediatric CPGs for depression with a minimum or high-quality level contained recommendations on nutrition, sleep or exercise. Lifestyle recommendations were predominately qualitative, with quantitative details only outlined in two CPGs for exercise. Most recommendations were brief general statements, with 50% lacking supporting evidence from the literature. CONCLUSIONS: Interest in lifestyle interventions for treatment in child and youth depression is growing. However, current CPG lifestyle recommendations for nutrition, sleep or exercise are based on expert opinion rather than clinical trials.

Problem-solving training as an active ingredient of treatment for youth depression: a scoping review and exploratory meta-analysis.

BACKGROUND: Problem-solving training is a common ingredient of evidence-based therapies for youth depression and has shown effectiveness as a versatile stand-alone intervention in adults. This scoping review provided a first overview of the evidence supporting problem solving as a mechanism for treating depression in youth aged 14 to 24 years. METHODS: Five bibliographic databases (APA PsycINFO, CINAHL, Embase, MEDLINE, Web of Science) and the grey literature were systematically searched for controlled trials of stand-alone problem-solving therapy; secondary analyses of trial data exploring problem-solving-related concepts as predictors, moderators, or mediators of treatment response within broader therapies; and clinical practice guidelines for youth depression. Following the scoping review, an exploratory meta-analysis examined the overall effectiveness of stand-alone problem-solving therapy. RESULTS: Inclusion criteria were met by four randomized trials of problem-solving therapy (524 participants); four secondary analyses of problem-solving-related concepts as predictors, moderators, or mediators; and 23 practice guidelines. The only clinical trial rated as having a low risk of bias found problem-solving training helped youth solve personal problems but was not significantly more effective than the control at reducing emotional symptoms. An exploratory meta-analysis showed a small and non-significant effect on self-reported depression or emotional symptoms (Hedges' g = - 0.34; 95% CI: - 0.92 to 0.23) with high heterogeneity. Removing one study at high risk of bias led to a decrease in effect size and heterogeneity (g = - 0.08; 95% CI: - 0.26 to 0.10). A GRADE appraisal suggested a low overall quality of the evidence. Tentative evidence from secondary analyses suggested problem-solving training might enhance outcomes in cognitive-behavioural therapy and family therapy, but dedicated dismantling studies are needed to corroborate these findings. Clinical practice guidelines did not recommend problem-solving training as a stand-alone treatment for youth depression, but five mentioned it as a treatment ingredient. CONCLUSIONS: On its own, problem-solving training may be beneficial for helping youth solve personal challenges, but it may not measurably reduce depressive symptoms. Youth experiencing elevated depressive symptoms may require more comprehensive psychotherapeutic support alongside problem-solving training. High-quality studies are needed to examine the effectiveness of problem-solving training as a stand-alone approach and as a treatment ingredient.

How have predictors, moderators, mediators, treatment response, remission and resistance been defined and measured in randomised controlled trials for adolescent depression? A scoping review protocol.

INTRODUCTION: Among randomised controlled trials for depressed adolescents, the extent of variation in how depressive symptom outcomes are defined is unknown. The variability in which potential predictors of these outcomes are tested is also unclear. This paper is a protocol describing the methods of a planned scoping review. The scoping review will examine and summarise how change in depressive symptoms have been described in RCT treatment studies to date. This review will report the measures used to describe change in depressive symptoms and whether the measure was used as a continuous or binary outcome or both. This review will describe how dichotomous outcome terms are defined to describe change in depression severity. This review will also examine predictors, moderators and mediators of change in depressive symptoms within RCTs. METHODS AND ANALYSIS: In this paper, we describe the protocol for our scoping review. Following the format outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews, a research librarian will develop an operationalised search strategy, which we will apply to the MEDLINE, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature databases. We will search for papers from inception to 6 February 2020. A hand search for key citations will also be conducted. Investigator-raters will screen articles, first via the titles and abstracts and then through full-text reviews. We will include articles with randomised control design which assess the treatment of adolescents with major depressive disorder. We will systematically extract and synthesise prespecified data which includes: definition of depression used for participant inclusion, measures used to evaluate changes in depression, type of outcome used (continuous, binary or both), definitions of dichotomous terms to denote change in depression (eg, response, remission, recovery, etc) and reported predictors/moderators/mediators of change. ETHICS AND DISSEMINATION: Ethics approval is not required. Findings will be presented in journal publications and at conferences.