Psychedelic drugs are serotonergic hallucinogens that can be divided into two types: naturally occurring (psilocybin, psilocin, and N,N-dimethyltryptamine) and synthetic (LSD, MDMA, 2,5-dimethoxy-4-iodoamphetamine, and ketamine). Psychedelics generally work on 5-hydroxytryptamine receptors and might be useful in cognitive enhancement, brain connectivity, neuroplasticity, and neuronal regeneration. These properties could be used in the pharmacological treatment of selected mental disorders. Autism spectrum disorders include a group of developmental disorders characterized by social communication issues, the presence of restricted interests as well as repetitive behaviors that impact the quality of life of patients and their caregivers. Currently, there are no authorized drugs for the treatment of the symptomatic features of ASD, but drugs are used for comorbid psychopathological aspects, but the efficacy and tolerability of such treatments are often questionable. Here, studies demonstrating the therapeutic utility of using psychedelic substances in autism are reported. These findings suggest a therapeutic potential of psychedelics for some aspects of symptoms associated with autism spectrum disorder.

Cannabis use represents a significant environmental risk factor for psychotic disorders, with emerging evidence suggesting complex interactions between cannabinoid exposure, dissociative experiences, and fundamental disturbances of self-experience (self-disorders) in early psychosis. This systematic review examines the phenomenological and neurobiological relationships among dissociation, cannabis use, and self-disturbance in first-episode psychosis (FEP) patients. Following PRISMA guidelines, we conducted a comprehensive search of four databases (PubMed, Scopus, PsycINFO, Web of Science) from January 1990 to September 2025, identifying 22 studies meeting inclusion criteria (total N = 3,847 participants). Results demonstrate that cannabis use, particularly high-potency THC products, is consistently associated with significantly elevated dissociative experiences compared to non-using FEP patients. Across studies employing the Dissociative Experiences Scale-II (DES-II), cannabis users showed score elevations of 11–13 points, exceeding clinically significant thresholds and persisting at follow-up assessments. Daily high-potency cannabis use was associated with three-fold increased odds of clinically significant dissociation (OR: 3.21, 95% CI: 2.14-4.82) and more severe anomalous self-experiences compared to non-using patients. Multiple mechanisms mediate these relationships: alterations in CB1 receptor availability and endocannabinoid system dysregulation in regions critical for self-awareness, disruption of neural networks supporting minimal self-consciousness, and acute psychotomimetic effects including depersonalization and derealization that may persist beyond intoxication periods. Cannabis-related dissociation shows distinct phenomenological characteristics compared to primary dissociative disorders, with greater self-world boundary confusion and more severe distortions of first-person perspective. Longitudinal studies indicate that persistent dissociative symptoms and self-disorders in cannabis-using FEP patients predict poorer functional outcomes (12-month GAF scores: 52 ± 14 vs. 67 ± 12 in non-users, p<0.001) and increased symptom chronicity. However, approximately 75% of patients showed dissociation reduction following cannabis cessation, suggesting potential reversibility. GRADE certainty of evidence was rated as moderate for dissociative symptom severity (downgraded for observational study designs) and low for self-disturbance outcomes (limited direct evidence with EASE assessment). This review highlights the importance of comprehensive phenomenological assessment in cannabis-using FEP patients, incorporating dissociative symptomatology and basic self-disturbance evaluation, with implications for early intervention strategies and targeted therapeutic approaches. Future research should employ longitudinal designs with repeated phenomenological assessments, biological verification of cannabis exposure, and integration of neuroimaging with experiential measures to elucidate causal mechanisms.

Mental health disorders frequently co-occur with oncological conditions, prompting an umbrella review(UR) to summarize meta-analytic evidence about the outcomes of pharmacological, psychosocial, and brain-stimulation interventions for psychiatric disorders in oncologic populations. We performed an UR of meta-analyses of randomized controlled trials(RCTs) documenting the efficacy of interventions for mental disorders in people with cancer(November 2, 2025). Re-calculated meta-analytic estimates employed the GRADE criteria for credibility. The AMSTAR-Plus Content Score was used to assess the quality of the meta-analyses. Overall, 82 meta-analyses(Number of records=111,331; primary studies=1,659) yielding 113 meta-analytic estimates were included. Five of 113 estimates were assigned a low level of certainty, and 108/113 were assigned a very low GRADE. Major depressive(55/113=48.67%) and any anxiety disorders(43/113=38.05%) emerged as the most frequently studied mental health diseases among the oncologic population. Mindfulness-based-stress-reduction for anxiety disorders in lung cancer was the only intervention significantly outperforming standard treatment(Hedges‘g=-1.46; 95%C.I.=-1.89;-1.04), whereas psychotherapy for women with breast cancer who underwent surgery was inferior to waiting list(in 80% of studies) in the treatment of anxiety due to women’s body image post-mastectomy(G=0.33; 95%C.I.=0.14; 0.52), with relatively higher credibility compared to other outcomes. Meta-regression suggested that psychotherapies might benefit females more than men, and that age might differentially moderate larger and smaller effects of psychotherapies in advanced cancer and any cancer, respectively. While MBSR shows relatively higher-level evidence for anxiety disorders in the oncological population, the level of evidence is low, underscoring the need for further research on alternative treatment modalities. CBT should be part of anxiety management following mastectomy.

Background and Objectives: Metacognition-related processes (e.g., confidence calibration, self-evaluation and the use of feedback) have been linked to cognitive insight, self-evaluation, and daily functioning in psychosis. However, clinic-based assessments only provide limited information. Digital methods may capture state-like variations and contextual factors, but it is unclear to what extent they operationalise core metacognitive monitoring constructs versus adjacent self-evaluative/insight-related constructs. We mapped digital approaches used to assess metacognition-related constructs across the psychosis spectrum, summarising the associated feasibility and validity. Materials and Methods: We conducted a scoping review (PRISMA-ScR) of psychosis-spectrum studies that used digital tools to assess metacognition-related targets. These included ecological momentary assessment/experience sampling (EMA/ESM), task-based paradigms with confidence ratings, and hybrid approaches. Searches covered MEDLINE (via PubMed), Scopus, and IEEE Xplore, with the final search run on 15 December 2025. We charted constructs, operationalisations, feasibility/engagement indices and reported links with clinical or functional measures. Results: The empirical evidence map comprised 13 studies directly assessing metacognition-related constructs; eight additional implementation/methodological sources were synthesised separately to contextualise feasibility, reporting, ethics, and governance. EMA studies more often assessed adjacent self-evaluative constructs, including context-linked self-appraisal bias, conviction, and self-report–context mismatch in daily life, whereas task-based studies more directly assessed confidence–accuracy calibration and feedback updating. Across EMA studies, greater momentary symptom severity and more restricted contexts were often associated with inflated self-evaluations and divergence from observer-rated functioning. Task-based studies indicated that confidence calibration and feedback utilisation may diverge from objective performance; in performance-controlled paradigms, some studies reported comparable metacognitive sensitivity/efficiency, but the overall evidence remains uncertain. Passive sensing was common in psychosis research but was rarely explicitly tied to metacognitive constructs. Conclusions: Current digital work spans both core metacognitive monitoring constructs and adjacent self-evaluative/insight-related constructs, rather than a single unitary construct. Clinical translation remains hypothesis-generating: interpretability may be improved by combining clinical anchors, low-burden EMA, and optional contextual streams, but thresholds, workflows, and signal-action rules require prospective validation.

Background and hypothesisCannabis use initiation during adolescence has increased globally, raising concerns about neurodevelopmental consequences during this critical period when the brain undergoes extensive remodeling in cannabinoid receptor-rich regions.Study designThis systematic review examines neurodevelopmental consequences of adolescent cannabis use, focusing on structural brain changes, cognitive impacts, addiction vulnerability, and long-term outcomes. We searched PubMed, EMBASE, PsycINFO, and Web of Science (2000-2025) for studies examining cannabis effects in adolescent populations. Following PRISMA guidelines, two reviewers screened 3,421 records and assessed 156 full-text articles, including studies with neuroimaging, cognitive assessments, or longitudinal follow-up.Study resultsThirty-six studies involving 8,432 participants met criteria: 23 longitudinal cohorts (62.2%), 8 cross-sectional (22.2%), 4 RCTs (11.1%), and 1 case-control study (2.8%). Neuroimaging revealed dose-dependent alterations including reduced prefrontal cortical and hippocampal/amygdala volumes, accelerated cortical thinning in longitudinal studies, and impaired white matter connectivity correlating with initiation age. Cognitive findings were mixed — some showed persistent deficits after prolonged abstinence in adolescent-onset users, others found no effects after controlling for confounders. Epidemiological studies consistently showed elevated addiction risk (ORs 3.9–7.2) in adolescents versus adults. Long-term associations included educational difficulties, mental health problems, and functional impairment, though causal relationships remained unclear.ConclusionsAdolescent cannabis use associates with structural brain changes, elevated addiction risk, and variable cognitive effects, suggesting greater vulnerability versus adult-onset use. However, methodological limitations including confounders, heterogeneous definitions, and observational designs limit causal inference. Findings support age-specific prevention and specialized interventions while highlighting needs for rigorous longitudinal research establishing causality.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifierCRD420251165329.

INTRODUCTION:Real-world evidence on desvenlafaxine effectiveness and tolerability in Major Depressive Disorder (MDD) remains limited, particularly in clinically heterogeneous populations. This multicentre observational study evaluated the real-world effectiveness and tolerability of desvenlafaxine, focusing on depressive and anxiety symptoms, response, remission, and side-effects burden. METHODS:This multicentre prospective observational study included 197 outpatients with DSM-5-TR Major Depressive Episode initiating desvenlafaxine. Assessments were conducted at baseline (T0), one month (T1), and three months (T2). Depressive symptoms (MADRS) were the primary outcome; anxiety (HAM-A), manic symptoms (YMRS), and tolerability (ASEC) were secondary outcomes. Response was defined as ≥50% MADRS reduction and remission as MADRS <10. RESULTS:Participants (mean age 46.1 ± 14.6 years; 55.3% female) showed clinically relevant baseline severity (MADRS 30.8 ± 7.3). MADRS scores decreased significantly over time in both unadjusted and adjusted models (both p < 0.005), with greater reductions at T2. A significant time × dose association was observed at T1 (p = 0.013), although no dose-related difference persisted at T2; prior hospitalisation was associated with attenuated improvement (p < 0.005). Anxiety symptoms improved significantly across follow-up (p < 0.005). Response and remission rates increased markedly from T1 to T2 (response: 12.4% to 66.7%; remission: 3.9% to 32.6%; both p < 0.005). Overall side-effect burden decreased significantly (p < 0.005), with reduced prevalence of most adverse events. Mean YMRS scores remained low throughout follow-up, with no clinically meaningful increase from baseline. CONCLUSIONS:In this multicentre real-world cohort, desvenlafaxine was associated with substantial improvements in depressive and anxiety symptoms, increasing response and remission rates, favourable tolerability. These findings support desvenlafaxine as an effective and well-tolerated treatment option in routine clinical practice.

BACKGROUND:The relationship between cannabis use and psychotic-like experiences (PLEs) remains a crucial area of investigation, particularly regarding different consumption patterns. METHODS:This cross-sectional study examined 150 participants divided into three groups: heavy cannabis users (n = 43), occasional users (n = 47), and non-users (n = 60). Participants were classified using CUDIT-R scores combined with self-reported frequency of use. Assessments included the Community Assessment of Psychic Experiences (CAPE) scale, Global Assessment of Functioning (GAF), and Clinical Global Impression (CGI) scales. Cannabis use patterns, age of onset, and duration were documented. RESULTS:Heavy users (mean age 23.6 ± 4.9 years) showed significantly higher scores on positive symptoms (38.4 ± 6.2) compared to occasional users (28.6 ± 5.4) and non-users (18.2 ± 4.2; p < 0.01; η2p = 0.24). Depressive symptoms were also elevated in heavy users (18.6 ± 3.8) versus occasional users (15.4 ± 3.2) and non-users (12.2 ± 2.8; p < 0.01; η2p = 0.19). No significant differences were found in negative symptoms across groups (p = 0.24; η2p = 0.02). Earlier age of onset (<16.4 years) correlated with increased PLEs (r = 0.27, p < 0.05) and poorer functioning. Heavy users demonstrated strong correlations between cannabis use frequency and both positive symptoms (r = 0.58, p < 0.01) and depressive symptoms (r = 0.52, p < 0.01). CONCLUSIONS:The findings suggest a frequency-related association between cannabis use and PLEs, particularly for positive and depressive symptoms. Early onset of use appears to be a significant risk factor for developing psychotic-like experiences, while negative symptoms remain largely unaffected. These results highlight the importance of considering consumption patterns when assessing the psychological impact of cannabis use.

Background/Objectives: The aim of this systematic review is to assess the efficacy, effectiveness, and safety of LAI antipsychotics in patients with schizophrenia and comorbid SUD, providing useful information for clinical decision making and guiding future research in the management of this complex patient population. Methods: The search was conducted on 1 July 2026 and produced 87 results in total; after the screening process, 78 articles were excluded based on the predefined eligibility criteria. The full texts of the remaining 9 studies were retrieved and thoroughly evaluated for inclusion in the qualitative synthesis. Results: The 9 articles that met the criteria for inclusion included 2062 patients in total with follow-up periods varying between 6 months and 3 years. Several studies reported favorable clinical outcomes associated with LAIs; however, not all studies demonstrated clear superiority of LAIs over oral antipsychotics. Conclusions: The present review suggests that LAIs may represent a valuable therapeutic strategy for patients with schizophrenia and comorbid SUD, although the available evidence remains heterogeneous in terms of study design, patient populations, and outcome measures.

Major depressive disorder is increasingly conceptualized as a condition involving brain network dysfunction, neuroimmune imbalance, sleep-circadian disruption, hypothalamic-pituitary-adrenal (HPA)-axis dysregulation, monoaminergic arousal instability, and impaired synaptic plasticity. In parallel, the glymphatic system has emerged as a plausible integrative mechanism linking these domains, because it is a glia-dependent pathway supporting cerebrospinal fluid-interstitial fluid exchange and metabolic-waste clearance, with activity strongly modulated by deep non-rapid eye movement (NREM) sleep. This narrative review synthesizes evidence that glymphatic-related magnetic resonance imaging (MRI) proxies, particularly diffusion tensor imaging along the perivascular space (DTI-ALPS), are altered in depression, while emphasizing that DTI-ALPS is an indirect marker of perivascular diffusion rather than a direct measure of glymphatic flow. We define four key research gaps: scarcity of treatment-resistant depression (TRD)-specific cohorts, regional and technical heterogeneity across MRI studies, and uncertainty about causal direction relative to sleep disturbance and inflammation. Altered indices appear to relate to fatigue, psychomotor retardation, cognitive impairment, rumination, suicidality, systemic inflammation, oxidative stress, and HPA-axis dysregulation. We integrate opposite-direction findings, including elevated ALPS in drug-naive somatic depression, into a state- and subtype-dependent working model rather than a unidirectional dysfunction framework. Therapeutic implications are organized by target specificity, including sleep-dependent clearance, perivascular exchange, aquaporin-4 (AQP4) polarization, vascular pulsatility, and neuroimmune modulation. We propose falsifiable predictions and negative-control analyses to distinguish a glymphatic-related model from additive effects of insomnia, inflammation, and vascular risk. Overall, the current evidence supports a cautious translational framework for biomarker-informed trials in TRD-relevant phenotypes rather than a validated diagnostic biomarker.

Eating disorders (EDs) disproportionately affect women and are associated with substantial morbidity, chronicity, and mortality. While established psychological models focus on the content of maladaptive cognitions related to body weight, shape, and eating behaviors, growing evidence suggests that additional process-level mechanisms contribute to symptom persistence and treatment resistance. Metacognitive models emphasize how individuals relate to their thoughts, emotions, and internal experiences, highlighting maladaptive beliefs about thinking and the resulting cognitive–attentional patterns (e.g., repetitive negative thinking, self-focused attention, and inflexible attentional control) as potential maintaining factors across psychopathology. This narrative review synthesizes the theoretical and empirical literature on metacognitive dysfunction in EDs, with a focus on mechanisms that may be particularly relevant for women. We integrate epidemiological data and gender-sensitive frameworks, and review evidence on metacognitive beliefs and cognitive–attentional syndrome (CAS)-related processes across anorexia nervosa, bulimia nervosa, and binge-eating disorder. Overall, studies indicate that dysfunctional beliefs about the uncontrollability and danger of thoughts, alongside perseverative cognitive styles, are associated with greater ED symptom severity. We discuss diagnosis-relevant patterns as clinically useful heuristics, interactions with sociocultural and emotional vulnerability factors, and implications for assessment, treatment integration, and prevention. The evidence base is largely correlational and derived from predominantly female samples, underscoring the need for longitudinal research and studies that explicitly test sex/gender as a moderator.

Background Cannabis-induced psychosis presents complex sex-based disparities that challenge traditional epidemiological patterns. While males demonstrate higher cannabis use rates, emerging evidence reveals paradoxical vulnerability patterns where females may show heightened susceptibility to cannabis-related psychotic outcomes despite lower consumption rates. Objective To map evidence for sex-specific vulnerability windows in cannabis-induced psychosis, examining neurobiological mechanisms, genetic factors, and developmental periods contributing to gender disparities. Methods We conducted a systematic search of major databases for studies published between 2000 and 2024 examining gender differences in cannabis-induced psychosis, regardless of whether such differences were a primary or secondary objective. Two independent reviewers screened articles and extracted data using standardized forms following scoping review methodology. Study characteristics, including methodological rigor, were charted using the Newcastle-Ottawa Scale as a descriptive indicator rather than a basis for weighted synthesis. Results From 2847 initial records, 30 studies met inclusion criteria and were analyzed. The review identified several sex-based paradoxes in cannabis-induced psychosis: (1) elimination of typical female advantage in age of psychosis onset; (2) sex-specific genetic vulnerabilities, particularly Brain Derived Neurotrophic Factor (BDNF) polymorphisms; (3) differential neurobiological responses to cannabis exposure; (4) age-dependent vulnerability patterns varying by gender. These findings challenge traditional risk models and reveal complex interactions between biological sex, developmental timing, and cannabis exposure. Conclusions Sex-specific vulnerabilities in cannabis-induced psychosis reflect complex interactions between hormonal factors, genetic polymorphisms, and developmental timing. These findings necessitate sex-specific approaches to prevention, assessment, and treatment.

Background The “critical window hypothesis” posits that prolonged duration of untreated psychosis (DUP) causes irreversible neurobiological damage during a time-sensitive period, leading to worse long-term outcomes. While widely accepted as justification for early intervention psychiatry, empirical evidence supporting this hypothesis remains contentious. This systematic review evaluates DUP-outcome relationships across symptomatic, functional, cognitive, and neurobiological domains. Methods Following PRISMA guidelines, we searched five databases through December 2025 for longitudinal studies examining DUP and outcomes at ≥12 months in first-episode psychosis. Study quality was evaluated using Newcastle-Ottawa Scale; findings were synthesized narratively due to substantial heterogeneity. Results From 8011 citations, 30 studies encompassing approximately 9800 first-episode psychosis patients were included. Longer DUP consistently associated with worse symptomatic outcomes at 1-2 years (median r = 0.20-0.35), but associations weakened substantially at 5-10 years. Functional outcomes showed modest associations (r = 0.15-0.25), primarily in social domains. Cognitive effects were minimal and inconsistent. Neuroimaging revealed gray matter reductions, though directionality unclear. Critical threshold analyses suggested inflection points at 6-12 months but varied considerably. Major limitations included retrospective DUP assessment, variable definitions, survivor bias, and inadequate confounder control (only 37% controlled premorbid functioning), substantially limiting causal inference. Conclusions While DUP shows consistent short-term associations, evidence for irreversible damage through critical window mechanisms remains inconclusive. Temporal attenuation suggests DUP may reflect illness severity and premorbid vulnerability rather than neurotoxicity. The field requires prospective studies with standardized measurement, adequate confounder control, and extended follow-up. Early intervention remains clinically justified through humanitarian principles, even if the critical window hypothesis lacks robust empirical support.

Background/Objectives: Although obsessive-compulsive disorder (OCD) is clinically heterogeneous, it is unclear whether specific metacognitive belief domains are differentially associated with particular symptom dimensions in adults with confirmed OCD. This systematic review synthesised the available clinical evidence and explored its implications for dimension-informed case formulation and treatment planning. Methods: In March 2026, PubMed/MEDLINE, Scopus, Cochrane CENTRAL and Google Scholar were searched without date or language restrictions. Eligible studies enrolled adults with a confirmed diagnosis of OCD, administered at least one validated metacognitive instrument (MCQ-30/65, TFI, TAF, BARI, SSQ or OBQ-based subscales) and reported associations with validated dimensional OCD measures. The review was preregistered on PROSPERO (CRD420261338178). Due to methodological heterogeneity, the findings were synthesised narratively in accordance with SWiM guidance. Results: Ten studies, including 1320 adults with OCD, were included. These studies were conducted across five countries between 2010 and 2025. Negative beliefs about thought uncontrollability and danger (MCQ-30 NB) showed the broadest associations across the synthesis, particularly with the checking/harm avoidance and the unacceptable thought dimensions. Thought-fusion constructs (TAF/TFI) were most consistently associated with checking/harm avoidance and unacceptable thought presentations. Beliefs about rituals and stop-signal criteria (BARI/SSQ) were most relevant to symmetry/ordering. In contrast, contamination/washing and hoarding exhibited weaker and less consistent metacognitive profiles. Conclusions: The available evidence suggests that metacognitive belief profiles in OCD are not dimensionally uniform. Harm-relevant metacognitions appear to be the most salient factor in the checking and unacceptable thought dimensions, whereas ritual-regulation metacognitions appear to be more relevant to the symmetry/ordering dimension. While these findings may inform dimension-sensitive case formulation and generate testable hypotheses for future metacognitive and exposure-based treatment research, they do not yet justify prescriptive, dimension-specific treatment algorithms. The evidence base remains predominantly cross-sectional and methodologically diverse.

This systematic review and meta-analysis synthesized data from 13 clinical trials (n=606) evaluating psilocybin-assisted psychotherapy for major depressive disorder and treatment-resistant depression. Despite early enthusiasm, the pooled standardized mean difference (-0.79, 95% confidence interval: -3.98 to 2.40, p=0.63) revealed no statistically significant overall antidepressant effect, with extreme heterogeneity (I2=96.9%) across studies. Notably, the type of control group (active comparator vs. placebo/waitlist) accounted for 98.7% of between-study variance, with waitlist and low-dose comparators producing exaggerated effect sizes. Session frequency was a significant moderator: 2 to 5 psilocybin sessions yielded larger effects, while more intensive protocols attenuated benefit. Neither participant age nor follow-up duration significantly influenced outcomes. Evidence of reporting bias and small-study effects was detected (Egger’s test p=0.012). Sensitivity analyses demonstrated that no single study accounted for the non-significant pooled result. Overall, psilocybin’s antidepressant efficacy appears highly context-dependent—shaped by trial design, comparator, and session structure—rather than universally robust. These findings underscore the need for larger, rigorously controlled trials to clarify psilocybin’s therapeutic role in depression.

Purpose: Treatment-resistant depression (TRD) is a common phenomenon and a considerable clinical challenge; recently, esketamine in conjunction with an oral antidepressant (AD) has emerged as a potential treatment for TRD. Several studies have shown the efficacy of esketamine in improving depressive symptoms. This prospective study aims to explore the long-term effects of esketamine therapy on subjective quality of life (QoL) and general status of adults with TRD. Methods: The study was an observational, prospective and multicenter study comprising a total of 18 TRD patients treated with Esketamine-Nasal Spray ESK-NS. Anamnestic data and psychometric assessments were collected at baseline (T0) and at follow-ups at 1 month (T1), 3 months (T2), and 6 months (T3). Results: Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF), Sheehan Disability Scale (SDS), and Personal and Social Performance Scale (PSP) showed a statistically significant amelioration in QoL and functioning for all 3 scales, with progressive improvements at 1, 3, and 6 months. Montgomery-Asberg Depression Rating Scale (MADRS) scores decreased from a baseline score of 39.2 to 28.7 on T1, 20.9 on T2, and 15.9 on T3, respectively. Correlation analyses showed statistical significance between changes at 6 months between MADRS and QLES and between MADRS and SDS, but not between MADRS and PSP. Conclusions: Significant improvement in QoL was observed among patients with TRD treated with ESK-NS; ESK-NS in combination with an oral AD appears to offer meaningful benefit as a treatment option for patients with TRD who generally have substantial QoL and functioning limitations as a result of their depressive illness

Background: Intranasal esketamine (ESK-NS) is an effective treatment for treatment-resistant depression (TRD), but whether antidepressant outcomes differ by sex and age remains insufficiently explored. Methods: This secondary analysis of the REAL-ESK study included 210 patients with TRD treated with ESK-NS in routine clinical practice and assessed at baseline (T0), one month (T1), and three months (T2). The primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) scores. Repeated-measures ANOVA tested Time and Time × Sex effects, with post-hoc contrasts corrected using the Holm procedure. Response and remission at T2 were compared by sex. Exploratory analyses stratified patients by age (<65 vs. ≥65 years). Results: MADRS scores decreased markedly over time (Time: F = 340.707, p < 0.005), with a significant Time × Sex interaction (F = 3.283, p = 0.043). At T2, men had lower MADRS scores than women (Δ = −3.95, Holm p = 0.023) and showed higher response and remission rates. In age-stratified analyses, sex differences were small and non-significant among participants <65 years. In those ≥65 years, the T2 contrast numerically favored men, but did not reach significance in post-hoc Holm’s correction and should be considered exploratory. Safety outcomes and discontinuation rates were broadly comparable between sexes. Conclusions: ESK-NS was associated with substantial antidepressant improvement in a real-world TRD cohort. Findings suggest a modest overall male advantage, while age-stratified patterns remain exploratory. Endocrine, vascular, inflammatory, pharmacokinetic, and treatment-context factors should be investigated in prospective studies.

The initial step in suicide prevention involves identifying individuals who may be at risk of attempting suicide at an early stage. Utilising artificial intelligence (AI) and machine learning (ML) techniques offers innovative avenues for the early detection of such individuals. Nevertheless, there is a lack of clear information regarding the application of AI and ML in suicide prevention. Our objective is to examine the latest research findings on the utilization of AI/ML in forecasting suicidal tendencies. Authors reviewed four databases (PubMed/MEDLINE, Scopus, Web of Science and SCImago) for studies using AI/ML for suicide prevention published in English from 1 January 2000 to 31 December 2021. Search strings and MeSH were employed for searching terms relevant to suicide prevention and AI/ML. Results of the studies were analysed qualitatively, and information was presented as tables and figures. After removing duplicate articles, out of 434 studies, 21 articles, involving a total of 274,876 participants, met the inclusion criteria and were considered for this review. The results suggested that AI/ML-based suicide prediction models might improve healthcare systems by identifying individuals at high risk of suicide by preventing suicidal attempts. However, further researches are needed to perform AI/ML-based evidence-based assessment tools and determine their validity and reliability for suicide prediction models in different contexts.

PURPOSE:Treatment-resistant depression (TRD) is a common phenomenon and a considerable clinical challenge; recently, esketamine in conjunction with an oral antidepressant (AD) has emerged as a potential treatment for TRD. Several studies have shown the efficacy of esketamine in improving depressive symptoms. This prospective study aims to explore the long-term effects of esketamine therapy on subjective quality of life (QoL) and general status of adults with TRD. METHODS:The study was an observational, prospective and multicenter study comprising a total of 18 TRD patients treated with Esketamine-Nasal Spray ESK-NS. Anamnestic data and psychometric assessments were collected at baseline (T0) and at follow-ups at 1 month (T1), 3 months (T2), and 6 months (T3). RESULTS:Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF), Sheehan Disability Scale (SDS), and Personal and Social Performance Scale (PSP) showed a statistically significant amelioration in QoL and functioning for all 3 scales, with progressive improvements at 1, 3, and 6 months. Montgomery-Asberg Depression Rating Scale (MADRS) scores decreased from a baseline score of 39.2 to 28.7 on T1, 20.9 on T2, and 15.9 on T3, respectively. Correlation analyses showed statistical significance between changes at 6 months between MADRS and QLES and between MADRS and SDS, but not between MADRS and PSP. CONCLUSIONS:Significant improvement in QoL was observed among patients with TRD treated with ESK-NS; ESK-NS in combination with an oral AD appears to offer meaningful benefit as a treatment option for patients with TRD who generally have substantial QoL and functioning limitations as a result of their depressive illness.

Background: Alcohol Use Disorders (AUD), affective disorders, and personality disorders are among the most prevalent mental health conditions observed in individuals exhibiting suicidal behavior, encompassing both completed and attempted suicides. A robust association between AUD and suicidal behavior has been established through retrospective and prospective cohort studies. Research on the relationship between alcohol consumption and self-harm has predominantly focused on Western and high-income countries, whereas approximately one-third of the global population, including half of the world's countries, lacks accessible suicide data. This study aims to present an updated review of empirical evidence regarding the risk of suicide associated with AUD in both developed and developing nations. Methods: We identified published meta-analyses, reviews, systematic reviews, randomized controlled trials, clinical studies, clinical trials, controlled clinical trials, observational studies, and case reports written in English and published between January 2004 and June 2024. Our search yielded a total of 312 papers. After reviewing titles and abstracts, 232 articles were excluded from the initial records. Following full-text review of the remaining 80 articles, a qualitative synthesis was conducted, highlighting the most representative 41 papers for inclusion in this overview. Results: Our analysis indicates that alcohol abuse is a significant risk factor for all forms of suicidal behavior. Alcohol consumption functions as both a predisposing and precipitating factor, contributing to maladaptive behaviors in both developing and developed countries. The clinical condition is exacerbated by alcohol use, which in turn increases the risk of suicide. Conclusions: Further research is essential to develop targeted psychological and pharmacological interventions aimed at preventing and treating these conditions, with the goal of reducing the risk of suicidal behavior associated with AUD. In developing countries, integrating public health and clinical strategies is crucial for effectively addressing suicide prevention.

The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA's blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.