Aug 2026· International Health Sciences Review· 0 citations
TL;DR
It is concluded that the management of ESRD should be individualized, based on up-to-date scientific evidence, and integrated with multidisciplinary approaches, aiming at symptom remission, functional recovery, and improvement of patients' quality of life.
Abstract
Treatment-resistant depression (TRD) represents one of the most complex forms of major depressive disorder, characterized by the persistence of clinically significant symptoms despite the performance of appropriate therapeutic interventions. This condition is associated with a worse prognosis, higher risk of recurrence, functional impairment, increased morbidity and mortality, and high socioeconomic impact. The objective of this article was to review the main aspects related to ESRD, addressing its definition, diagnostic criteria, epidemiology, pathophysiological mechanisms, and currently available therapeutic strategies. A narrative review of the literature was carried out, including national and international studies that discuss advances in the management of resistant depression. It is observed that the pathophysiology of ESRD involves alterations in mon oaminergic and glutamatergic neurotransmission, reduced neuroplasticity, inflammatory processes, neuroendocrine dysfunctions, and genetic factors, justifying the limited efficacy of conventional antidepressants in some patients. Current therapeutic strategies include optimization and combination of antidepressants, pharmacological potentiation, use of atypical antipsychotics, lithium, and thyroid hormones, as well as innovative therapies such as ketamine and esketamine, which demonstrate rapid antidepressant response in selected cases. It is concluded that the management of ESRD should be individualized, based on up-to-date scientific evidence, and integrated with multidisciplinary approaches, aiming at symptom remission, functional recovery, and improvement of patients' quality of life.
Treatment-resistant depression (TRD) represents one of the most severe forms of major depressive disorder and is associated with high morbidity and mortality, functional impairment, increased suicidal ideation, and significant socioeconomic impacts. In this context, ketamine and esketamine have emerged as innovative therapeutic alternatives due to their rapid antidepressant effect and their potential to reduce suicidal ideation within a few hours of administration. The aim of this study was to critically analyze the available scientific evidence regarding the therapeutic use of ketamine and esketamine in treatment-resistant depression, emphasizing their clinical efficacy, mechanisms of action, safety profile, and future prospects. A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. Searches were conducted in the PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and PsycINFO databases, using search terms related to treatment-resistant depression, ketamine, esketamine, NMDA receptors, neuroplasticity, and suicidal ideation. After applying the eligibility criteria, 92 studies were included for qualitative analysis. The evidence demonstrated that both intravenous ketamine and intranasal esketamine promote a rapid and significant reduction in depressive symptoms and suicidal ideation, especially in patients with multiple treatment failures. The mechanisms of action involve modulation of glutamatergic neurotransmission, activation of AMPA receptors, increased expression of brain-derived neurotrophic factor (BDNF), and restoration of brain neuroplasticity. The main adverse events were transient dissociative symptoms, temporary elevation of blood pressure, nausea, and dizziness, presenting a favorable safety profile when used under specialized monitoring. It is concluded that ketamine and esketamine represent important therapeutic advances in the treatment of treatment-resistant depression, particularly due to the rapid clinical response and the potential to reduce the risk of suicide. However, further studies are needed to define optimal maintenance protocols, assess long-term safety, and expand the use of these therapies in evidence-based clinical practice.
Marcos A. Couto, Flávia Eduarda Pereira Januário, Gabriela de Luna Costa Pinheiro et al.· International Journal of Pha...· 0 citations
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.
Helena Victor Leite Panadés, Isadora Queiroz Graça, Maria Fernanda Vasconcelos Mascarenhas Clementino et al.· Revista de Estudos Interdisc...· 0 citations
When conventional treatments are ineffective for treating treatment-resistant depression, ketamine offers quick and strong results, marking a paradigm change in psychiatric care.
Prachi Tayal, Rina Das, M. Khan et al.· Current pharmaceutical desig...· 0 citations
Bipolar disorder (BD) is a chronic, recurrent psychiatric illness characterized by episodes of mania, hypomania, and depression that substantially impair psychosocial functioning and quality of life. Pharmacotherapy remains the cornerstone of both acute symptom management and long-term relapse prevention. Over the past decade, advances in clinical trials and international treatment guidelines have refined the role of mood stabilizers, second-generation antipsychotics, and adjunctive therapies across different phases of illness. This review summarizes the current clinical pharmacology of bipolar disorder, emphasizing mechanisms of action, pharmacokinetic and pharmacodynamic properties, efficacy, safety, and monitoring requirements of established and emerging pharmacological treatments. Attention is given to lithium, anticonvulsant mood stabilizers, second-generation antipsychotics, the management of bipolar depression, treatment-resistant bipolar disorder, medication adherence, and individualized treatment selection. Recent evidence regarding suicide prevention, renal safety, reproductive considerations, and novel therapeutic strategies is integrated with current guideline recommendations to provide an evidence-based framework for optimizing long-term clinical outcomes.
Michel Bourin· Journal of Psychology and Ps...· 0 citations
Major depressive disorder (MDD) is a common health disorders characterized by anhedonia along with physical changes. MDD is a leading cause of disability worldwide. MDD treatment mainly focuses on improving the quality of life of the patients suffering from this disorder. Various modalities of treatment include initiating pharmacotherapy, focussed psychotherapy, or electroconvulsive therapies. The current treatment modalities focus on the monoamine hypothesis with a wide range of drugs available from tricyclic antidepressants (TCAs) to selective serotonin reuptake inhibitors (SSRIs). Despite therapy with the currently available drugs a substantial proportion of patients do not achieve full remission with full-dose titration and there is still persistence of treatment-resistant depression (TRD). The currently available antidepressants drugs are associated with frequent adverse effects with tolerance limiting their long-term adherence. Delivery of psychotherapy has its own set of limitation and one of them is in form of delivery of psychotherapy. As many patients despite optimal therapy of currently available antidepressant drugs one-third of the patients do not respond to the currently available forms of therapy. The understanding of the pathophysiology has increased our knowledge with role of neuroplasticity, disrupted signalling pathway, decreased neurotropic factor expressions and altered functional connectivity of neurocircuitry also playing its role apart from the neurotransmission theory of depression. Opening up avenues for treatment of currently unanswered area for depression which include lag in onset of effect, tolerance to therapy, treatment resistant depression and delay in achieving remission. The current review tries to highlight the various options for treatment of depression for effective treatment of depression.
International Journal of Human and Health Sciences Vol. 10 No. 04 Oct’26 Page: 217-226
Jaspreet Kaur, Deepika Puri, K. Sachdeva et al.· International Journal of Hum...· 0 citations
The review underscores the need for longitudinal research, refined diagnostic frameworks, and context-sensitive implementation strategies to advance holistic, patient-centered management of depression in schizophrenia.
Oshi Malik, Priyanka Yadav· Indian Journal of Medical Sp...· 0 citations
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