The neurobiological synergy of transcranial magnetic stimulation and mindfulness-based interventions in treatment-resistant depression: a narrative review

Treatment-resistant depression (TRD) poses a significant challenge, with many patients failing to achieve remission with conventional therapies. While repetitive Transcranial Magnetic Stimulation (rTMS) is an established and effective neuromodulatory treatment for TRD, a notable proportion of patients do not fully respond. Despite the clinical utility of rTMS, response variability remains a significant barrier to treatment optimization. We propose that this variability may be driven, in part, by fluctuations in baseline network configuration and momentary brain states. This motivates the investigation of behavioral state manipulation as a means to prime neural circuits for enhanced receptivity to neuromodulation. This mini-review proposes that combining TMS with adjunctive, short-duration mental practices, specifically Mindfulness Based Interventions (MBI), may enhance therapeutic outcomes. Given that both TMS and mindfulness converge on modulating brain networks regulating emotions, attention and self-referential processes, it is plausible that their concurrent or sequential use could yield additive or even synergistic effects on network reorganization. We will explore the theoretical neurobiological mechanisms that may support a potential synergistic or additive effect and synthesize the limited but promising evidence from analogous therapeutic combinations to argue for the clinical viability of this novel approach. This review aims to: (1) Summarize the shared network targets (DMN, CEN, and SN) of rTMS and mindfulness; (2) Propose a state-dependent synergy model for their integration; and (3) Synthesize existing evidence to guide future clinical trial design.