📋 Browse Articles

Ketamine has emerged as a promising rapid-acting antidepressant with distinct advantages for the treatment of treatment-resistant depression (TRD). Its therapeutic effects are mediated through multi-target modulation of the glutamatergic system. Unlike conventional antidepressants, ketamine exerts a markedly faster onset of action; however, its long-term safety profile and potential risk of dependence require rigorous evaluation. This scoping review aims to systematically summarize recent advances in research on ketamine's role in depression treatment. This review synthesizes current evidence regarding ketamine's molecular mechanisms of action, neuroimaging correlates, pharmacological characteristics, and associated ethical considerations. By primarily antagonizing N-methyl-D-aspartate (NMDA) receptors, ketamine rapidly disinhibits the mesolimbic dopamine reward pathway and upregulates brain-derived neurotrophic factor (BDNF) expression via eukaryotic elongation factor 2 kinase (eEF2K) suppression, thereby activating the mammalian target of rapamycin (mTOR) pathway and enhancing synaptic plasticity. Neuroimaging studies further reveal that ketamine induces rapid remodeling of prefrontal-limbic functional connectivity, modulates default mode network activity, and promotes the normalization of cerebral metabolism and structure. Pharmacologically, ketamine exhibits a rapid onset of action and a relatively broad therapeutic window, though notable pharmacodynamic and pharmacokinetic differences exist between its enantiomers and active metabolites, which warrants further investigation. Ketamine displays rapid onset and high efficacy in the management of TRD; nevertheless, its long-term safety, risk of dependence, and potential cognitive effects necessitate close clinical monitoring. Future research should prioritize the exploration of synergistic treatment regimens and the development of novel ketamine derivatives with improved target specificity and safety profiles to advance the application of precision psychiatry. Collectively, this review provides a foundational reference to guide clinical practice and inform subsequent mechanistic studies on ketamine-based antidepressant therapies. Show less

Treatment-resistant depression (TRD) remains a complex challenge, often requiring interventions beyond standard medications. This review explores factors that may predict positive response to electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS) and ketamine-based treatments to help guide clinical decision-making. A systematic review was conducted following PRISMA 2020 guidelines. English-language, peer-reviewed studies were identified through PubMed, Embase and Google Scholar using search terms such as 'treatment-resistant,' 'outcome,' 'prediction,' 'ECT,' 'rTMS,' and 'ketamine.' Studies were included if they examined clinical, biological or imaging predictors of response in adults with TRD. Case reports, reviews, editorials and non-English articles were excluded. A total of 42 studies were selected from 408 screened. Among these, 23 focused on ketamine/esketamine, 14 on rTMS, and 11 on ECT. Predictive factors were grouped into clinical (e.g., symptom profile, illness duration), biological (e.g., IL-6, CRP, BDNF) and imaging (e.g., cingulate cortex activity, connectivity). Inflammation markers and fronto-limbic network findings appeared across treatments, though findings were inconsistent. While some predictors show promise, clinical use remains limited by methodological differences and small sample sizes. Larger studies are required to identify clinically useful predictors. Additionally, for optimal treatment decision-making, comparative studies are necessary. Show less