For adults with difficult-to-treat depression—those who have not responded to prior treatments, have treatment-resistant depression, or have a chronic course—mindfulness-based cognitive therapy (MBCT) is likely superior to usual care, reducing depressive symptoms by a standardized mean difference of -0.40 at post-treatment and -0.41 at medium-term follow-up. There was a 92% and 85% probability, respectively, that these benefits exceeded a minimal important difference. However, MBCT did not show clear superiority over other active psychosocial interventions, and no robust moderators of outcome were identified across baseline severity, chronicity, or comorbidity.
Intranasal esketamine is a newer treatment for Treatment-Resistant Depression (TRD), but its long-term benefits in real-world settings remain uncertain. A 6-month observational study of 60 highly chronic and complex TRD patients (average episode length 41.2 months, 61.6% with psychiatric comorbidity) found that depression scores (MADRS) dropped from an average of 33.9 at baseline to 15.7 at 6 months. Patients who had not responded to prior electroconvulsive therapy (ECT) showed no significant difference in therapeutic response compared to those who had not tried ECT. The findings suggest that intranasal esketamine may be worth testing promptly in TRD patients who have not responded to ECT.