Non-implantable neuromodulation therapies compared to conventional treatments for major depression

Depression remains a leading cause of disability worldwide. Conventional treatments, such as pharmacotherapy and psychotherapy, are first-line interventions but are limited by partial efficacy, tolerability issues, and delayed onset of action. In this context, non-implantable neuromodulation techniques can be an important tool in clinical practice addressing some of these limitations, and are the scope of this review.

This review synthesizes evidence on non-implantable neuromodulation for major depressive disorder, covering established modalities (ECT, MST, rTMS, tDCS, tACS) and emerging approaches (FUS, PBM, tTIS, PNS and tPEMF). Mechanisms, efficacy, tolerability, and accessibility are discussed. PubMed/MEDLINE was searched from inception to 1 November 2025, prioritizing systematic reviews, randomized trials, major guidelines, and large observational studies, with reference-list screening.

Non-implantable neuromodulation therapies are evolving from experimental interventions to validated clinical options. Rather than competing with pharmacotherapy, they should be viewed as complementary components within a multimodal framework. The future of depression management likely depends on the integration of pharmacological and neuromodulatory approaches to optimize response, tolerability, and functional recovery.