PHARMACOLOGICAL APPROACHES TO TREATMENT-RESISTANT DEPRESSION

Abstract

Treatment-resistant depression (TRD) is a form of Major Depressive Disorder that does not respond to conventional therapies. Although there are several definitions and models to classify TRD, all agree that it is characterized by an inadequate response to at least two antidepressant treatments. The objective of this article is to review the pharmacological therapeutic options to treat resistant depressive disorder. A literature review was performed in the main medical databases using the descriptors “pharmacological” and “treatment-resistant depression”, using the Boolean operator “AND”. All articles published between 2024-2025 were included in the primary analysis. It is observed that the target of integrated therapeutic strategies, which include medication optimization, a combination of antidepressants, and antidepressant switching, is one of the alternatives for managing these cases. Likewise, studies have analyzed new approaches, such as the use of ketamine, psilocybin, and anti-inflammatories. However, treatment continues to challenge mental health professionals, and more relevant research involving new medications is needed to improve the quality of life of patients with the disorder.