Drug repurposing in the management of major depressive disorder: a perspective

We review the literature regarding repurposed medications for major depressive disorder (MDD). Preclinical and clinical research on repurposed medications for MDD was reviewed, including agents that modulate the dopaminergic, glutamatergic, and GABAergic systems; enhance neurotrophic signalling; and reduce neuroinflammation, as well as nutraceuticals. Telmisartan, statins, celecoxib, valproic acid, pregabalin, metformin, pioglitazone, ketamine, dextromethorphan-bupropion, aripiprazole, and modafinil show effectiveness in the treatment of MDD, as do nutritional supplements such as vitamin D, zinc, selenium, and spermidine. Mechanisms include neurotransmission modulation, neuroplasticity promotion, and neuroinflammatory cascade suppression. However, the current evidence is limited by a lack of large-scale randomised controlled trials and insufficient mechanistic characterisation. Drug repurposing leverages proven safety profiles while reducing development costs and time. Nonetheless, clinical studies are needed to confirm effectiveness, elucidate mechanisms, and specify their incorporation into clinical practice.