Examining What Works for Whom and How in Mindfulness-Based Cognitive Therapy (MBCT) for Recurrent Depression: A Moderated-Mediation Analysis in the PREVENT Trial (in press)

Background: Personalized management of recurrent depression, considering individual patient characteristics, is crucial. Aims: This study evaluates the potentially different mediating role of mindfulness skills in managing recurrent depression using mindfulness-based cognitive therapy (MBCT) among patients with varying depression severity. Method: Data from the PREVENT trial, comparing MBCT (with antidepressant medication (ADM) tapering support, MBCT-TS) vs. maintenance-ADM, was used. The study included pre, post, 9-, 12-, 18-, and 24-month follow-ups. Adult patients with ≥3 previous major depressive episodes, in full/partial remission (below threshold for a current episode), on ADM, were assessed for eligibility in primary care practices in the UK. Patients were randomized (1:1) to MBCT-TS or maintenance-ADM. We used the Beck Depression Inventory-II to evaluate depressive symptom changes over the six time points. Pre-post treatment, we employed the Five Facets of Mindfulness Questionnaire to gauge mindfulness skills. Baseline symptom and history variables were used to identify patients with varying severity profiles. We conducted Latent Profile Moderated-Mediation Growth Mixture Models. Results: A total of 424 patients (mean (SD) age=49.44 (12.31) years; with 325 (76.7%) self-identified as female) were included. A mediating effect of mindfulness skills, between trial arm allocation and the linear rate of depressive symptoms change over 24 months, moderated by depression severity, was observed (moderated-mediation index=-0.27, 95%CI=-0.66, -0.03). Conditional indirect effects were -0.42 (95%CI=-0.78, -0.18) for higher severity (expected mean BDI-II reduction=10 points), and -0.15 (95%CI=-0.35, -0.02) for lower severity (expected mean BDI-II reduction=3.5 points). Conclusions: Mindfulness skills constitute a unique mechanism driving change in MBCT (vs. maintenance-ADM). Patients with higher depression severity may benefit most from MBCT-TS for residual symptoms. It is unclear if these effects apply to those with a current depressive episode. Future research should investigate individuals who are not on medication. This study provides preliminary evidence for personalized management of recurrent depression.