A conceptual framework based on current and emerging treatments for treatment-resistant depression: mechanistic evolution, clinical evidence, and future directions.
Expert Review of Neurotherapeutics July 1, 2026 Stephen Rush, Henry A Nasrallah
Treatment-resistant depression (TRD) represents an unmet challenge, accounting for disproportionate morbidity, disability, and healthcare burden in depression. Limitations of monoaminergic antidepressants have prompted a conceptual shift toward models emphasizing impaired neuroplasticity, synaptic dysfunction, and network dysregulation. This expert review synthesizes preclinical, translational,...