INTEGRATION OF PHARMACOLOGICAL THERAPIES WITH MULTIMODAL NON-PHARMACOLOGICAL APPROACHES IN HEART FAILURE
Introduction: Treatment-resistant depression (TRD) is characterized by the persistence of depressive symptoms following at least two adequate therapeutic trials with distinct classes of antidepressants. Given the limited efficacy of the traditional monoaminergic model and the high socioeconomic and functional burden of the disease, interventions with rapid mechanisms of action have become imperative. Objective: To evaluate the comparative efficacy of electroconvulsive therapy (ECT) and ketamine regarding neurobiological adaptations and therapeutic resistance in TRD. Methodology: An integrative literature review was conducted in the PubMed and SciELO databases using strategic combined descriptors. Original articles in English published between 2020 and 2025 addressing pharmacological mechanisms, neuroplasticity, clinical efficacy, and safety were selected. Results: Evidence points to a progressive decline in response to conventional antidepressants with each treatment failure. In non-psychotic conditions, intravenous ketamine demonstrated non-inferiority and higher remission rates compared to ECT. Both modalities promoted a rapid reduction in suicidal ideation within the first 24 hours. However, ECT maintained superiority in severe episodes accompanied by psychotic features or catatonia. Longitudinal analysis revealed a progressive loss of the acute therapeutic effect post-induction, with lower relapse rates in the ketamine group at six months. At the molecular level, both therapies converge in inducing BDNF, hippocampal neurogenesis, and modulating the adenosine-mediated purinergic pathway. From an economic perspective, both proved cost-effective by reducing hospital readmissions. Discussion: The disparity in outcomes across studies stems from the phenotypic heterogeneity of TRD, where the presence of psychotic symptoms drastically alters the biological response. The identification of adenosinergic signaling as a shared link supports the rapid speed of neuroplastic response. Furthermore, contrasting tolerability profiles—such as cognitive events with ECT versus transient dissociative symptoms with ketamine—and high relapse rates underscore the necessity for structured maintenance protocols. Conclusion: Ketamine and ECT constitute complementary rather than competing tools. Therapeutic choice must be individualized, considering clinical profiles, the presence of psychosis, tolerability, and the mandatory requirement for maintenance therapy.