Efficacy and Moderators of Mindfulness-Based Cognitive Therapy (MBCT) in Difficult to Treat Depression: Protocol for a Systematic Review and Individual Patient Data Meta-Analysis of Randomised Controlled Trials

IntroductionAbout 30% of depressed patients suffer from a protracted course in which the disorder continues to cause significant burden despite treatment efforts. While originally developed for relapse prevention, Mindfulness-Based Cognitive Therapy (MBCT) has increasingly been investigated in depressed patients with such difficult-to-treat courses. This is a protocol for an individual participant data (IPD) meta-analysis aiming to determine efficacy and potential moderators of MBCT treatment effects in this group based on evidence from randomised controlled trials. Methods and analysisSystematic searches in PubMed, Web of Science, Scopus, PsycINFO, EMBASE, and the Cochrane Controlled Trials Register for randomised controlled trials were completed on 17 June 2024. Authors of identified studies have contributed IPD and data extractions have been completed. An update search will be conducted immediately before the start of data analyses. We will investigate the following outcomes: (a) self-reported and observer-reported severity of depression symptomatology, (b) remission, (c) clinically meaningful improvement and deterioration. One-stage and two-stage IPD meta-analyses will be conducted with one-stage models using the observed IPD from all studies simultaneously as the primary approach. One-stage IPD models will include stratified study intercepts and error terms as well as random effects to capture between-study heterogeneity. Moderator analyses will test treatment-covariate interactions for both individual patient level and study level characteristics. Ethics and disseminationThe results will inform understanding of the use of MBCT in patients with current difficult-to-treat depression and will contribute to arguments in favour of or against implementing MBCT as a treatment for this group. They will be published in a peer reviewed journal and made available to stakeholders in accessible formats. No local ethical review was necessary following consultation with the Ethics and Governance Board of the University of Surrey. Guidance on patient data storage and management will be adhered to throughout. PROSPERO registration numberCRD42022332039 STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThe chosen approach using IPD has several advantages over conventional meta-analyses including the possibility to assess whether individual participant level characteristics influence treatment effects with more specificity and power C_LIO_LILimitations of the approach include the fact that inconsistencies across studies regarding the format and type of variables reported may restrict our ability to investigate moderators of treatment effects C_LIO_LITransformation of outcome measures to a common metric across all studies may come with a small loss of information. C_LI