Cognitive behavioral therapies (CBT) represent a heterogeneous group of psychotherapies in continuous development that share a directive, structured, collaborative approach. Due to a high degree of treatment-resistant cases of major depressive disorder (MDD), new augmentation therapies are urgently needed, in order to increase the chance of recovery in these patients.

To analyze data that may support the indication of third wave CBT in patients with MDD.

A literature search was performed in the main electronic databases, and papers published between January 2000 and August 2020 were included.

Acceptance and commitment therapy has been associated with positive results, but data are derived from low quality trials (n=2). Dialectical-behavioral therapy (DBT)-based skill group have been also associated with favorable outcome, in MDD patients (n=2). Mindfulness-based cognitive therapy (MBCT) was also proven effective in the treatment in MDD (n=4), treatment-resistant MDD included, but the difference between MBCT and active comparators was not always significant. Metacognitive therapy (MCT) has been evaluated in good quality clinical trials (n=4), and its efficacy was confirmed. Mild and moderate MDD patients may benefit from compassion-focused therapy (CFT) (n=1). Behavioral activation (BA) is dedicated to MDD patients and according to a meta-analysis (n=26 randomized controlled trials) BA is superior to other active comparators, although the quality of clinical trials was modest.

Third generation CBT could be useful in MDD patients as augmentative strategy, but more good-quality data are necessary before recommending them in an evidence-based treatment guideline as a distinctive intervention from classical CBT.