Efficacy and moderators of mindfulness-based cognitive therapy (MBCT) in 'Difficult to Treat' depression: protocol for a systematic review and individual participant data meta-analysis of randomised controlled trials.
Thorsten Barnhofer, Maria Niemi, Johannes Michalak, Maria Velana, J Mark G Williams, Alberto Chiesa, Stuart J. Eisendrath, Kevin L. Delucchi, Zindel V. Segal, Mira B. Cladder-Micus, Anne E. M. Speckens, Ali Akbar Foroughi, Mauro Garcia-Toro, Jesus Montero-Marin, Barney Dunn, Clara Strauss, Florian Alexander Ruths, Mary Ryan, Mathias Harrer
BMJ Open December 8, 2025 DOI: 10.1136/bmjopen-2025-106350 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review protocol (individual participant data meta-analysis) Randomized Peer reviewed |
|---|---|
| Population | Patients with current difficult-to-treat depression, as studied in randomised controlled trials of MBCT |
| Intervention | Mindfulness-based cognitive therapy (MBCT) |
| Topics | Depression Meditation |
| Keywords | Humans Treatment outcome Research design Meta-analysis as topic Depressive disorder, treatment-resistant Cognitive behavioral therapy |
| Key findings | The protocol aims to determine the efficacy of MBCT and potential moderators of its treatment effects in patients with difficult-to-treat depression, using individual participant data from randomised controlled trials. The authors state the results will contribute to arguments in favour of or against implementing MBCT as a treatment for this group. |
Abstract
Introduction: About 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 analysis: Systematic 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 and (c) clinically meaningful improvement and deterioration. One-stage and two-stage IPD-MA 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 dissemination: The 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 number: CRD42022332039.
Comparable studies
Other systematic reviews and meta-analyses on depression, most cited first.