Treatment-Resistant Depression: A Psychiatry Perspective on Pathophysiological Mechanisms, Biomarkers, and Novel Therapeutic Frontiers
DOI:
https://doi.org/10.63501/54mphj57Abstract
Treatment-resistant depression (TRD) represents a major clinical and public health challenge, affecting a substantial proportion of patients with major depressive disorder who fail to achieve remission despite adequate pharmacotherapy. Emerging evidence suggests that TRD is a heterogeneous condition driven by complex interactions among neurobiological, inflammatory, and psychosocial factors. Advances in understanding pathophysiological mechanisms—including neuroinflammation, synaptic dysfunction, and neuroendocrine dysregulation—have facilitated the identification of potential biomarkers and the development of novel therapeutic strategies. This perspective explores current insights into the mechanisms underlying TRD, highlights promising biomarkers for diagnosis and treatment stratification, and discusses emerging therapeutic frontiers such as rapid-acting antidepressants, neuromodulation, and psychedelic-assisted therapy. Integrating these advances into clinical practice may enable a more personalized and effective approach to managing TRD.
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