New Antidepressant Development in the Treatment of Depression.
Advances in experimental medicine and biology January 1, 2026 Alessandro Spiti, Daniela Caldirola, Giampaolo Perna 1 citation
Major depressive disorder (MDD) remains difficult to treat due to its varied symptoms. Antidepressant development began with electroconvulsive therapy, monoamine oxidase inhibitors, and tricyclic antidepressants, which targeted the monoaminergic system but had safety and efficacy limits. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors improved tolerability yet left unmet needs like treatment resistance. Research then expanded to new mechanisms: NMDA receptor antagonists such as ketamine and esketamine provide fast-acting effects through glutamatergic modulation; GABA modulation via neurosteroids like zuranolone offers a new approach for postpartum depression; kappa-opioid receptor antagonism is...