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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 Cladder-micus, Anne 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 Peer reviewed DOI: 10.1159/000552831 via OpenAlex

Summary

Mindfulness-based cognitive therapy (MBCT) is likely more effective than treatment as usual (TAU) for patients with treatment-resistant depression, showing a standardized mean difference of -0.40 at post-treatment and -0.41 at medium-term follow-up. However, MBCT did not show superiority over other psychosocial interventions. The study involved data from seven trials with a total of 777 participants, indicating that MBCT could be a valuable addition to treatment options for difficult-to-treat depression.

Study at a glance

Design meta-analysis
Sample size 777
Population currently depressed adults with treatment non-response or resistance
Key finding MBCT was likely superior to TAU for treating treatment-resistant depression, with benefits maintained at medium-term follow-up.

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.

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