An individual patient data (IPD) meta-analysis on negative effects of Mindfulness-Based Cognitive Therapy (MBCT) and Cognitive Behavior Analysis of Psychotherapy (CBASP) for patients with difficult-to-treat depression (DTD)

ABSTRACT Background Chronic and treatment-resistant depression remains a challenge. Although research has demonstrated positive effects of Mindfulness-Based Cognitive Therapy (MBCT) and Cognitive Behavioral Analysis System of Psychotherapy (CBASP), their potential negative effects—including deterioration, suicidality, and adverse events—are not well understood.

Objectives: This protocol outlines an individual patient data (IPD) meta-analysis to assess and compare the incidence and correlates of negative effects of MBCT and CBASP in adults with chronic and treatment-resistant forms of depression, subsumed under the wider heuristic of difficult-to-treat depression. Secondary aims include examining effects on depressive symptoms across these interventions and identifying moderators of negative outcomes.

Methods: Randomized controlled trials (RCTs) of MBCT and CBASP for adults (18–65 years) with chronic or treatment-resistant depression will be identified through systematic searches of major databases. Eligible studies must compare MBCT or CBASP (alone or with treatment as usual) to each other or to control groups. The primary outcome is clinically significant deterioration, defined as a ≥6-point increase on the PHQ-9 or equivalent. Secondary outcomes are suicidality, adverse events, and depressive symptom change. IPD will be requested from authors; aggregate data will be used if IPD is unavailable. One-stage random effects meta-analyses and moderator analyses will be conducted.

Discussion: This IPD meta-analysis will provide robust estimates of negative effects for MBCT and CBASP in DTD, informing clinical practice and guidelines on patient safety. PROSPERO registration number CRD42022332039 Strengths and limitations Leveraging an individual patient data (IPD) meta-analysis allows for more precise assessment of negative effects and enables detailed moderator analyses that are not possible with aggregate data approaches. Standardizing outcome measures across studies using a common metric enhances comparability but may result in some loss of information or sensitivity to subtle differences in negative outcomes. Differences in the availability and reporting of individual-level variables across studies may limit the ability to fully explore all potential moderators of negative effects, and reliance on data sharing from original authors could restrict the inclusion of eligible studies.