Transitioning from conventional therapies to nanomedicine-based therapeutics for major depressive disorder

Major depressive disorder (MDD) is a common, debilitating psychiatric disorder characterized by persistent sadness, anhedonia, and functional impairment, affecting millions of individuals worldwide and constituting a leading cause of disability. This review summarizes conventional approaches for the prevention and treatment of MDD, encompassing pharmacotherapy with various classes of antidepressants and psychotherapeutic interventions such as cognitive-behavioural therapy (CBT). Although these interventions demonstrate efficacy, their clinical utility is frequently constrained by delayed onset of action, adverse effects, and partial or absent response in a substantial proportion of patients. Nanomedicine has emerged as a promising therapeutic avenue for MDD; it entails the use of neuro-targeted nanoparticles to enhance drug bioavailability. Such nanosystems may overcome limitations of conventional therapies by enabling spatiotemporally controlled release of antidepressants within the brain. Nevertheless, before widespread clinical adoption, the safety profile, long-term sequelae, and complex biocompatibility of these materials require rigorous elucidation. The review additionally discusses the contribution of animal models, particularly zebrafish, to neurobiological investigations of depression. Such models are indispensable for recapitulating depressive phenotypes, delineating MDD pathophysiology, and assessing candidate therapeutics, including nanomedicines. In conclusion, although established MDD therapies remain fundamental, nanomedicine offers substantial promise; however, additional research and optimization are imperative to ensure its safe and efficacious clinical translation.