Novel drug developmental strategies for treatment‐resistant depression
British Journal of Pharmacology November 25, 2021 Éva Borbély, Mária Simon, Eberhard Fuchs et al. 103 citations
Major depressive disorder is a leading cause of disability worldwide, and conventional therapies fail many patients, especially those with treatment-resistant depression (TRD). This review examines novel drug targets and candidates in Phase I–III clinical trials. The most promising approaches include blocking glutamatergic neurotransmission with NMDA and mGlu5 receptor antagonists, modulating the opioidergic system with κ receptor antagonists, and using hallucinogenic tryptamine derivatives. The only registered drug for TRD is the NMDA receptor antagonist S-ketamine, but add-on therapies with second-generation antipsychotics, nutritive, anti-inflammatory, and neuroprotective agents also appear effective. Ongoing large-scale omics and neuroimaging studies may reveal new molecular mechanisms and therapeutic strategies.