Modern Approaches to Depression: From Monoamines to Medicinal Plants and Neuromodulation

Abstract

One of the most common mental health conditions in the world, depression severely reduces social functioning,
productivity, and personal well-being. Over 300 million people are impacted globally, and by 2040, it is
expected to overtake all other causes of disability. A thorough discussion of major depression, also known as
major depressive disorder, is given here, along with an examination of its complex etiology, which includes
genetic, neurochemical, and sociocultural factors. Its pathogenesis is primarily characterized by the dysregulation
of the hypothalamic-pituitary-adrenal axis, glutamatergic signaling, and monoaminergic transmitters including
dopamine, serotonin, and norepinephrine. Due to their delayed onset, adverse effects, and resistance to therapy,
conventional antidepressant therapies such as selective serotonin reuptake inhibitors, serotonin-norepinephrine
reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors remain first-line treatments. In
addition, this review covers new approaches to treatment, including psychedelic-assisted therapy, brain stimulation
techniques such as electroconvulsive therapy, transcranial magnetic stimulation, deep brain stimulation, and vagus
nerve stimulation and rapid-acting pharmaceuticals such as ketamine and esketamine. The use of medicinal plants
such as Withania somnifera, Curcuma longa, Hypericum perforatum, and others demonstrates promise due to their
multi-targeted action, safety, and accessibility. These phytochemicals modulate neurotransmitter activity, reduce
oxidative stress, and support neurotrophic factors. A holistic and personalized treatment approach, integrating
pharmacotherapy, neurostimulation, and complementary herbal medicine, may optimize outcomes in depression
management. Addressing stigma, increasing early diagnosis, and ensuring mental health-care accessibility remain
imperative. Future research should focus on novel drug targets, patient-tailored therapies, and bridging the gap
between traditional and modern practices.