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

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.