Physical Therapies and Neuromodulation for Treatment-Resistant Schizophrenia: A Review of Potential Mechanisms, Efficacy, and Safety.

Antipsychotic medications remain the conventional treatment for treatment-resistant schizophrenia (TRS), yet some patients exhibit poor responses. Due to the limitations of pharmacological interventions, physical therapies are increasingly recognized as essential supplements in managing TRS. This article systematically examines the current clinical applications and research advances of physical therapeutic techniques for TRS. Existing evidence suggests that electroconvulsive therapy (ECT), particularly when administered as an adjunct to antipsychotic medication, may improve positive symptoms and overall clinical outcomes in a subset of patients with TRS. However, its potential cognitive adverse effects and related ethical considerations warrant careful evaluation. As a non-invasive neuromodulatory technique, transcranial magnetic stimulation (TMS) may exert therapeutic effects by modulating frontotemporal cortical excitability and activity within associated neural circuits, thereby contributing to improvements in auditory hallucinations, negative symptoms, and cognitive function. Transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS), is characterized by procedural simplicity, favorable safety, and good tolerability. Its clinical effects may be mediated through modulation of cortical excitability, synaptic plasticity, and functional connectivity. However, current studies remain highly heterogeneous with respect to sample size, stimulation parameters, treatment duration, outcome measures, and follow-up periods. Moreover, no physical therapy has yet been approved by the US. Food and Drug Administration (FDA) for the treatment of TRS. This article aims to synthesize the therapeutic efficacy of various physical interventions for TRS and summarize the current clinical evidence, thereby broadening the range of potential treatment options for patients with TRS and promoting a more comprehensive clinical understanding and management of this condition.