Zofia Kachlik

Treatment-resistant depression (TRD) and bipolar depression (TRBD) are severe, heterogeneous mood disorders associated with substantial functional impairment, elevated suicide risk and persistent unmet treatment needs. While pharmacological and psychological interventions continue to advance, many patients experience delayed, partial or unsustained benefit, underscoring the need for therapies with novel mechanisms and rapid onset of action. Ketamine and esketamine have emerged as distinctive treatments in this context, demonstrating rapid antidepressant and anti-suicidal effects, yet differing fundamentally from conventional antidepressants in their acute subjective effects, physiological profile, delivery models and misuse potential. This narrative review synthesizes evidence from regulatory guidance, clinical trials, observational studies and qualitative research to identify key patient information needs and propose practical psychoeducational strategies. Core elements include explanations of indications, mechanisms and treatment algorithms; guidance on visit preparation, scheduling and monitoring; management of acute adverse effects; counselling on suicidality and substance misuse; and tailored considerations for special populations, including older adults, women of reproductive potential and medically complex patients. Drawing on this synthesis, the review proposes a patient-centred framework for ketamine and esketamine psychoeducation, outlining key informational domains and practical tools that can be embedded within clinical services, and identifies priorities for future research aimed at optimizing patient experience and supporting the responsible integration of ketamine-based therapies into mood disorder care.

Background: Anhedonia is a key symptom of bipolar depression and a target of ketamine’s rapid antidepressant effects. However, many patients with treatment-resistant bipolar depression (TRBD) do not respond. Objectives: This study aimed to identify clinical and sociodemographic characteristics that are associated with nonresponse of anhedonia following short-term ketamine treatment in TRBD. Design: A retrospective analysis using data from two naturalistic, observational registries of 31 patients with TRBD and baseline anhedonia (Snaith-Hamilton Pleasure Scale (SHAPS) > 2). Patients received eight doses of ketamine (IV: 0.5 mg/kg; oral: 2.0–2.5 mg/kg) over a short-term treatment course. Methods: Patients were classified as responders or nonresponders based on a ⩾50% reduction in SHAPS score by the seventh ketamine dose. Groups were compared on baseline sociodemographic and clinical features. Results: Fourteen patients (45.2%) did not respond. Nonresponders had higher BMI, later illness onset, fewer hypomanic episodes, and lower employment rates. Conclusion: Metabolic, illness-course, and psychosocial factors may predict reduced anti-anhedonic response to ketamine in TRBD.

Treatment-resistant depression (TRD) remains a significant public-health challenge, with many patients failing to respond to conventional therapies. Ketamine has emerged as a rapid-acting intervention, but quantitative outcomes alone do not capture patients’ lived experiences, which shape engagement, acceptability, and adherence. We conducted a narrative review of qualitative and mixed-methods studies to enable conceptual integration and thematic synthesis of patients’ experiences with ketamine treatment for depression, guided by established narrative review methodology and the SANRA framework. A targeted search of MEDLINE and Scopus (November 2025) identified studies reporting adult patients’ perspectives on therapeutic ketamine or esketamine use, with qualitative data synthesized iteratively in keeping with narrative review principles. Across the literature, patients’ perspectives coalesce around key thematic domains, including motivations and expectations for treatment, the phenomenology of the treatment experience, post-treatment trajectories, side effects and reasons for discontinuation, relational and environmental factors, and information and education needs. By focusing on these thematic groups, the review highlights the experiential dimensions that influence the perceived value and acceptability of ketamine, underscoring the need for patient-centered service design. Integrating these insights can guide the development of ketamine programs that are both evidence-based and aligned with patients’ priorities and perspectives.

Background: Suicide remains a leading cause of death among youth, yet effective tools to predict suicide attempts (SA) in individuals under 18 are scarce. This study aims to develop machine learning (ML) models to predict SA in paediatric populations using Google Trends data. Methods: Relative Search Volumes (RSVs) from Google Trends were analysed for terms linked to suicide risk factors. Pearson Correlation Coefficients (PCC) identified terms strongly associated with SA rates. Based on these, several ML models were developed and evaluated, including Random Forest Regression, Support Vector Regression (SVR), XGBoost, and Linear Regression. Model performance was assessed using metrics such as PCC, mean absolute error (MAE), mean squared error (MSE), root mean square error (RMSE), and mean absolute percentage error (MAPE). Results: Terms related to suicide prevention and symptoms, including psychiatrist and anxiety disorder, showed the strongest correlations with SA rates (PCC ≥ 0.90). Random Forest Regression emerged as the top-performing ML model (PCC = 0.953, MAPE = 20.12%, RMSE = 17.21), highlighting burnout, anxiety disorder, antidepressants, and psychiatrist as key predictors of SA. Other models’ scores were XGBoost (PCC = 0.446, MAPE = 22.57%, RMSE = 18.03), SVR (PCC = 0.833, MAPE = 42.23%, RMSE = 47.32) and Linear Regression (PCC = 0.947, MAPE = 23.64%, RMSE = 17.66). Conclusions: Google Trends–based ML models suggest potential utility for short-term prediction of youth SA. These preliminary findings support the utility of search data in identifying real-time suicide risk in paediatric populations.

Objectives: Ketamine is a prototypical rapid‐acting antidepressant for treatment‐resistant bipolar depression (TRBD), yet many patients do not achieve a meaningful response. This study explored features of ketamine nonresponse in TRBD. Methods: In a post hoc analysis of a naturalistic study, 35 TRBD patients received a four‐week ketamine regimen (intravenous 0.5 mg/kg or oral 2.0/2.5 mg/kg). Response was measured using the Montgomery‐Åsberg Depression Rating Scale, and baseline sociodemographic and clinical features were compared between responders and nonresponders. Results: Fourteen patients (40%) were nonresponders. They had a higher median number of psychiatric comorbidities (2 vs. 1; p = 0.0366), were more likely to have any psychiatric comorbidity (78.6% vs. 33.3%; p = 0.0153), and had greater prior benzodiazepine use (64.3% vs. 23.8%; p = 0.0332). No significant links emerged between individual comorbidities or baseline suicidality and response. Conclusion: Ketamine demonstrates a favorable safety and tolerability profile for short time use in TRBD regardless of isolated baseline characteristics, although a more severe comorbidity burden and benzodiazepine use appear to be associated with nonresponse. Trial Registration: NCT04226963 and NCT05565352

Background: Fecal microbiota transplantation (FMT) from humans with specific medical conditions to animal models can demonstrate causality by inducing or exacerbating pathophenotypes, linking the gut microbiota to health outcomes. Methods: We conducted a scoping review searching MEDLINE, EMBASE, Scopus, and Web of Science through July 2024 to identify human noninfectious diseases studied using FMT in animal models, investigate FMT methodologies, and assess the feasibility of systematic reviews on the role of the microbiota in specific diseases. Results: From 605 reports of 489 studies, we found that inflammatory bowel diseases, irritable bowel syndrome, obesity, colorectal cancer, and depression were the most commonly studied, with cancer research focusing on immunotherapy non-responsiveness. In a random sample of studies, gastrointestinal outcomes were most frequently reported, with remarkably high rates (> 80%) of successful induction of disease-specific alterations for intestinal barrier function, gastrointestinal inflammation, circulating immune parameters, and fecal metabolites. Most studies used C57BL/6 mice and oral gavage administration, with recipients being either germ-free or antibiotic-pretreated. We created tables linking conditions with publications to facilitate future systematic reviews. Conclusions: Although human-to-animal FMT studies cover diverse conditions, methodological heterogeneity and inconsistent reporting hinder comparability. Standardized protocols and guidelines are needed. For several conditions, sufficient literature exists to assess the role of the gut microbiota in human health through systematic reviews.

Background: Ketamine is currently gaining attention as a rapid-acting antidepressant for treatment-resistant depression (TRD). However, many patients fail to respond, and limited data exist on predictors of non-response. This study aims to characterize the sociodemographic and clinical features associated with non-response to ketamine among TRD patients. Methods: This is a post-hoc analysis of a naturalistic observational study, which enrolled 40 inpatients with treatment-resistant major depressive disorder and analyzed sociodemographic and clinical features in responders and non-responders stratified per Montgomery-Åsberg Depression Rating Scale (MADRS) during short-term ketamine administration (intravenous dosage: 0,5 mg/kg and orally: 2.0 or 2.5 mg/kg) that comprise over 4 weeks. Results: In this study, 30 patients (75%) were classified as non-responders. No significant differences were detected among sociodemographic and clinical features beyond the history of substance use disorder (SUD) – only 53.3% of non-responders reported prior SUD (vs. 100%; p = 0.0075) and a lower number of psychiatric comorbidities (p = 0.0381). Conclusion: This study highlights key characteristics of TRD non-responders to ketamine, including lower rates of SUD and fewer psychiatric comorbidities. These findings suggest that a higher burden of traditional TRD risk factors may not limit ketamine efficacy and could even enhance response compared to “pure” major depressive disorder. Identifying potential non-responders early can optimize treatment decisions, reduce ineffective exposure, and guide future research on improving TRD management.