Unveiling mechanisms of change in digital interventions for depression: Study protocol for a systematic review and individual participant data meta-analysis.

Introduction: The efficacy and effectiveness of digital interventions for depression are both well-established. However, precise effect size estimates for mediators transmitting the effects of digital interventions are not available; and integrative insights on the specific mechanisms of change in internet- and mobile-based interventions (IMIs)-as related to key features like delivery type, accompanying support and theoretical foundation-are largely pending. Objective: We will conduct a systematic review and individual participant data meta-analysis (IPD-MA) evaluating the mediators associated with therapeutic change in various IMIs for depression in adults. Methods: We will use three electronic databases (i.e., Embase, Medline/PubMed, PsycINFO) as well as an already established database of IPD to identify relevant published and unpublished studies. We will include (1) randomized controlled trials that examine (2) mediators of (3) guided and unguided (4) IMIs with (5) various theoretical orientations for (6) adults with (7) clinically relevant symptoms of depression (8) compared to an active or passive control condition (9) with depression symptom severity as primary outcome. Study selection, data extraction, as well as quality and risk of bias (RoB) assessment will be done independently by two reviewers. Corresponding authors of eligible primary studies will be invited to share their IPD for this meta-analytic study. In a 1-stage IPD-MA, mediation analyses (e.g., on potential mediators like self-efficacy, emotion regulation or problem solving) will be performed using a multilevel structural equation modeling approach within a random-effects framework. Indirect effects will be estimated, with multiple imputation for missing data; the overall model fit will be evaluated and statistical heterogeneity will be assessed. Furthermore, we will investigate if indirect effects are moderated by different variables on participant- (e.g., age, sex/gender, symptom severity), study- (e.g., quality, studies evaluating the temporal ordering of changes in mediators and outcomes), and intervention-level (e.g., theoretical foundation, delivery type, guidance). Discussion: This systematic review and IPD-MA will generate comprehensive information on the differential strength of mediators and associated therapeutic processes in digital interventions for depression. The findings might contribute to the empirically-informed advancement of psychotherapeutic interventions, leading to more effective interventions and improved treatment outcomes in digital mental health. Besides, with our novel approach to mediation analyses with IPD-MA, we might also add to a methodological progression of evidence-synthesis in psychotherapy process research. Study registration with Open Science Framework OSF: https://osf.io/md7pq/.