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Efficacy and Moderators of Mindfulness-Based Cognitive Therapy in Difficult-to-Treat Depression: A Systematic Review and Individual Participant Data Meta-Analysis

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, Mauro Garcia-Toro, Jesus Montero-Marin, Barnaby D. Dunn, Clara Strauss, Florian A Ruths, Mary Ryan, Allan H. Young, Pim Cuijpers, Mathias Harrer

Psychotherapy and Psychosomatics June 12, 2026 DOI: 10.1159/000552831 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Individual patient data (IPD) meta-analysis of randomized controlled trials Peer reviewed
Sample size 777
Population Currently depressed adults meeting criteria for treatment non-response, treatment resistance, or chronic course
Interventions Mindfulness-based cognitive therapy treatment as usual other active psychosocial controls
Topics Depression Meditation
Keywords Psychosocial Psychological intervention Moderation Cognitive behavioral therapy Randomized controlled trial Depression economics Relapse prevention Clinical psychology Meta-analysis Cognition Mindfulness-based cognitive therapy Psychotherapist
Citations 1
Key findings Mindfulness-based cognitive therapy was likely superior to treatment as usual for reducing depressive symptom severity in difficult-to-treat depression, but not clearly superior to other active psychosocial interventions.

Abstract

Introduction: Around a third of patients with major depressive disorder experience persistent symptoms despite usual treatments. Identifying scalable, psychological treatment options is critical to reduce the burden associated with difficult-to-treat depression (DTD). We examined the efficacy of mindfulness-based cognitive therapy (MBCT) compared with treatment as usual (TAU) and other active psychosocial controls in current DTD, and explored potential moderators.

Methods: We conducted an individual patient data (IPD) meta-analysis of randomised controlled trials comparing MBCT with TAU or other active psychosocial controls in currently depressed adults meeting criteria for treatment non-response, treatment resistance, or chronic course. Seven studies (N = 777) contributed data. Bayesian one-stage models were used as primary approach to estimate pooled effects on depressive symptom severity.

Results: MBCT was likely superior to TAU at post-treatment (standardised mean difference = -0.40; 95% credible interval [CrI] = -0.64 to -0.16) and medium-term follow-up (-0.41; 95% CrI = -0.76 to -0.02), with posterior probabilities of 92% and 85% of surpassing a minimal important difference (d = -0.24), respectively. In contrast, comparative effects relative to other psychosocial interventions were uncertain, with no evidence of superiority. Moderator analyses did not identify robust predictors of outcome, suggesting broadly consistent effects across baseline severity, chronicity, and comorbidity.

Conclusions: MBCT appears to be an effective and safe option for DTD, superior to TAU, with benefits maintained at medium-term follow-up, although no evidence of superiority over other active psychosocial interventions was observed. These findings support the integration of MBCT into comprehensive treatment models for DTD.

Comparable studies

Other systematic reviews and meta-analyses on depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188

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