NEW ANTIDEPRESSANTS AND GLUTAMATERGIC MODULATORS FOR GERIATRIC DEPRESSION

Abstract

The present study is a systematic literature review that investigates the efficacy and safety of new antidepressants and glutamatergic modulators in the treatment of Major Depression (MD) in geriatric patients, with a focus on individuals with Treatment-Resistant Depression. The methodology followed the PRISMA protocol, using databases such as PubMed and Scopus, with a search of articles published between 2020 and 2024 and the use of key terms such as “Older adults,” “Major depression,” “Treatment-resistant depression,” “Glutamatergic modulators,” and “Esketamine.” The findings confirm that MD in older adults is characterized by synaptic dysfunction and neuroinflammation, limiting the effectiveness of conventional monoaminergic treatments. The emergence of esketamine represents a crucial breakthrough, demonstrating ultrarapid and robust action in cases of TRD by restoring synaptic neuroplasticity. However, its use in the elderly population requires strict monitoring due to the risk of transient increases in blood pressure and dissociation. Alternatively, new non-monoaminergic agents, such as agomelatine, offer cleaner safety profiles, making them ideal for long-term management and for patients undergoing polypharmacy. The conclusion is that the management of geriatric depression requires a personalized approach that combines the rapid action of glutamatergic modulators with the safety of new agents for maintenance, prioritizing tolerability and the preservation of cognitive function in order to reverse therapeutic resistance and improve quality of life.