Combined transcranial direct current stimulation and embodiment-based psychotherapy on interoceptive awareness and depressive symptoms in patients with major depressive disorder: a randomized, sham-controlled clinical trial

Major depressive disorder (MDD) is associated with impaired interoceptive processing, contributing to emotional dysregulation and disturbed bodily experience. Although transcranial direct current stimulation (tDCS) and embodiment-based psychotherapy (EPT) have each shown therapeutic potential, their independent and combined effects have not been compared within a single trial. This study investigated the independent and combined effects of tDCS and EPT on interoceptive awareness and depressive symptoms in individuals with MDD. In this randomized, sham-controlled, assessor-blinded trial, 40 individuals with MDD were randomly assigned to one of four groups: tDCS, EPT, combined tDCS + EPT, or sham. Following the withdrawal of two participants, 38 individuals (18 women, 20 men) completed the study. Participants received either 10 sessions of active tDCS (2 mA, 20 min, anode F3 / cathode Fp2), 8 sessions of EPT, both interventions concurrently, or sham stimulation. Interoceptive awareness (primary outcome) and depressive symptoms (secondary outcome) were assessed before and after treatment using the Multidimensional Assessment of Interoceptive Awareness (MAIA) and the Beck Depression Inventory-II (BDI-II). Data were analyzed using a descriptive mixed-design ANOVA and a pre-specified ANCOVA with Bonferroni-corrected pairwise comparisons; an exploratory 2 × 2 factorial ANCOVA tested the EPT × tDCS interaction. Groups differed on the primary outcome, F(3, 33) = 14.87, p < .001, η² p = .575, and on the secondary outcome, F(3, 33) = 44.35, p < .001, η² p = .801. Relative to sham, interoceptive awareness improved in the Combined group (adjusted mean difference 23.24, 95% CI 12.87 to 33.61), the EPT group (19.86, 9.30 to 30.43) and the tDCS group (12.61, 2.02 to 23.20). Depressive symptoms decreased relative to sham in the Combined group (− 15.82, − 20.50 to − 11.13) and the EPT group (− 15.73, − 20.40 to − 11.06), both of which also outperformed tDCS alone. For depressive symptoms, the covariate-adjusted comparison between tDCS and sham was nominally significant (− 5.56, − 10.44 to − 0.69, p = .018) but did not replicate in the unadjusted analysis of change over time ( p = 1.000); tDCS alone is therefore not considered to have produced a confirmed reduction in depressive symptoms relative to sham. The Combined group did not differ from EPT alone on either outcome (both p = 1.000). In the exploratory factorial model, both main effects were significant, but the EPT × tDCS interaction did not indicate synergy on either outcome. EPT, delivered alone or with concurrent tDCS, was associated with large improvements in interoceptive awareness and depressive symptoms relative to sham. Adding tDCS to EPT conferred no detectable additional benefit, and the data provide no support for a synergistic effect. Because the trial was powered only for active-versus-sham comparisons, the comparison between the combined and EPT groups is inconclusive rather than null. This trial was registered in the Iranian Registry of Clinical Trials (IRCT20170417033485N3, registered on 2025/10/16).