Confronting the unmet therapeutic needs in major depressive disorder- New antidepressants in clinical practice and promises from the pipeline

Although depressive disorders benefit from a large variety of therapeutic agents launched in clinical practice in the last six decades, the rates of non-responsiveness and partial response are still high. A new wave of antidepressants has been approved in the last 5 years by various national or regional agencies with responsibilities in the field of medicines authorization, for depressive disorders (major depressive disorder, postpartum depression, and treatment-resistant depression)- gepirone, esketamine, toludesvenlafaxine, zuranolone, brexanolone, and the combination dextromethorphan+bupropion. The available, limited data, support the efficacy and safety of these new pharmacological agents, but extensive research is needed in order to evaluate their long-term clinical effects. Other investigational products with anti-depressive properties are explored in preclinical studies and clinical trials, such as monoaminergic agents, orexin receptor antagonists, anti-cytokines, sestrin modulators, glutamatergic agents, cholinergic receptor modulators, etc. Original studies, case series, reviews, and meta-analyses focused on exploring such agents are expected to enrich the current knowledge on this topic with important clinical consequences.

13/11/2026