Molecular Mechanisms of Emerging Antidepressant Strategies: From Ketamine to Neuromodulation
International Journal of Molecular Sciences December 28, 2025 Mateusz Kowalczyk, David Aebisher, Jakub Szpara et al. 3 citations
Depression is a common and potentially life-threatening disorder affecting over 300 million people worldwide, with major depressive disorder increasing suicide risk. Its causes involve genetic vulnerability, chronic stress, HPA axis dysregulation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and impaired synaptic plasticity. This review synthesizes data on pharmacological treatments—including SSRIs, SNRIs, TCAs, and MAOIs—and emerging therapies targeting glutamatergic, GABAergic, and dopaminergic systems, such as ketamine, esketamine, dextromethorphan-bupropion, neurosteroids, and selective receptor modulators. It also covers non-pharmacological neuromodulation like TMS, tDCS, and photobiomodulation, integrating molecular mechanisms with depression pathophysiology to inform precise, multimodal treatment strategies.