PHARMACOLOGICAL APPROACHES TO TREATMENT-RESISTANT DEPRESSION

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, especially in young adults. The pharmacological management of TBI aims to minimize secondary damage through strategies that reduce cerebral edema, inflammation, neuronal apoptosis, and mitochondrial dysfunction. This review aims to present and discuss the main pharmacological approaches investigated in the treatment of TBI. A literature review was performed in the main medical databases using the descriptors “traumatic brain injury”, “pharmacological” and “therapy”, using the Boolean operator “AND”. All articles published between 2020-2025 were included in the primary analysis. Several pharmacological agents have been studied in the context of TBI, with varying degrees of efficacy. Corticosteroids, widely used in the past, have shown increased mortality in large clinical trials. Progesterone and erythropoietin have demonstrated neuroprotective benefits in animal models, but have not shown consistent positive results in phase III clinical studies. Drugs such as amantadine, N-acetylcysteine, minocycline, propranolol, vitamin D, metformin and cerebrolysin have shown potential beneficial effects on neurological recovery, with some promising data in humans. However, the heterogeneity of studies and the lack of standardized protocols still limit definitive clinical recommendations. Despite advances in understanding the pathophysiological mechanisms of TBI, effective pharmacological options remain limited. Agents with antioxidant, anti-inflammatory and neuroprotective properties have shown promise, especially when used early. More robust clinical studies are needed to validate the efficacy and safety of these interventions and to establish clear therapeutic guidelines for the pharmacological treatment of TBI.