Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia

JAMA Psychiatry, Journal Year: 2024, Volume and Issue: 81(8), P. 749 - 749

Published: May 1, 2024

Importance A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M 1 /M 4 preferring muscarinic receptor agonist no direct D 2 dopamine blocking activity. KarXT combines xanomeline the peripheral antagonist trospium chloride goal reducing adverse events due to xanomeline-related activation. In prior trials, xanomeline-trospium was effective in symptoms psychosis generally well tolerated people schizophrenia. Objective To evaluate efficacy safety vs placebo adults Design, Setting, Participants EMERGENT-3 ( NCT04738123 ) phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial schizophrenia experiencing acute psychosis, conducted between April 1, 2021, December 7, 2022, at 30 inpatient sites US Ukraine. Data were analyzed from February June 2023. Interventions randomized 1:1 receive (maximum dose 125 mg/trospium mg) or 5 weeks. Main Outcomes Measures The prespecified primary end point change baseline week Positive Negative Syndrome Scale (PANSS) total score. Secondary outcome measures PANSS positive subscale score, negative Marder factor Clinical Global Impression–Severity proportion participants least 30% reduction Safety also evaluated. Results 256 (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 [60.9%] Black African American, 98 [38.3%] White, [0.4%] Asian) (125 group 131 group). At 5, significantly reduced score compared (xanomeline-trospium , −20.6; placebo, −12.2; squares mean difference, −8.4; 95% CI, −12.4 −4.3; P < .001; Cohen d effect size, 0.60). Discontinuation rates treatment-emergent (TEAEs) similar (8 [6.4%]) (7 [5.5%]) groups. most common TEAEs nausea (24 [19.2%] [1.6%]), dyspepsia (20 [16.0%] vomiting participant [0.8%]), constipation (16 [12.8%] [3.9%]). extrapyramidal symptoms, weight gain, somnolence treatment Conclusions Relevance Xanomeline-trospium efficacious psychosis. These findings, together previously reported consistent results EMERGENT-1 EMERGENT-2 support potential be first putative class without Trial Registration ClinicalTrials.gov Identifier:

Language: Английский

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Negative symptoms and social cognition as mediators of the relationship between neurocognition and functional outcome in schizophrenia

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 31, 2024

Introduction In this study we assessed the contribution of psychopathology, including two domains negative symptoms (motivational deficit and expressive deficit), processing speed as an index neurocognition, emotion recognition, social cognition, to poor functional outcomes in people with schizophrenia. Methods The Positive Negative Syndrome Scale was used evaluate positive disorganization Brief Symptom assess symptoms. Symbol Coding Trail Making Test A B were rate Facial Emotion Identification recognition. Functional outcome Personal Social Performance (PSP). Regression analyses performed identify predictors outcome. Mediation investigate whether cognition symptom fully or partially mediated impact on Results One hundred fifty subjects from 8 different European centers recruited. Our data showed that predicted global functioning together motivational effects neurocognition it. Motivational a predictor personal neurocognitive impairment same Both socially useful activities, recognition domain deficits Conclusions results indicate pathways are specific for real-life mediate functioning. suggest both should be targeted by psychosocial interventions enhance remediation.

Language: Английский

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Multidimensional outcome of first-episode psychosis: a network analysis

Psychological Medicine, Journal Year: 2025, Volume and Issue: 55

Published: Jan. 1, 2025

Abstract Background Few studies have examined the long-term outcomes of first-episode psychosis (FEP) among patients beyond symptomatic and functional remission. This study aimed to broaden scope outcome indicators by examining relationships between 12 FEP at 20.9 years after their initial diagnosis. Methods At follow-up, 220 out 550 original underwent a new assessment. Twelve were assessed via semistructured interviews complementary scales: symptom severity, impairment, personal recovery, social disadvantage, physical health, number suicide attempts, episodes, current drug use, dose-years antipsychotics (DYAps), cognitive motor abnormalities, DSM-5 final The these measures investigated using Spearman’s correlation analysis exploratory factor analysis, while specific connections ascertained network analysis. Results significantly correlated; specifically, functioning, recovery showed strongest correlations. Exploratory revealed two factors, with 11 loading on first factor. Network that diagnosis, DYAps, episodes most interconnected outcomes. Conclusion provided insights into heterogeneity FEP. By considering rich net interconnections elucidated herein can facilitate development interventions target potentially modifiable generalize impact

Language: Английский

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The structure stability of negative symptoms: longitudinal network analysis of the Brief Negative Symptom Scale in people with schizophrenia

BJPsych Open, Journal Year: 2023, Volume and Issue: 9(5)

Published: Sept. 1, 2023

The structure of negative symptoms schizophrenia is still a matter controversy. Although two-dimensional model (comprising the expressive deficit dimension and motivation pleasure dimension) has gained large consensus, it been questioned by recent investigations.To investigate latent its stability over time in people with using network analysis.Negative were assessed 612 Brief Negative Symptom Scale (BNSS) at baseline 4-year follow-up. A invariance analysis was conducted to changes strength connections between two points.The carried out follow-up, supported community detection analysis, indicated that BNSS's items aggregate form four or five distinct domains (avolition/asociality, anhedonia, blunted affect alogia). test remained unchanged (network score 0.13; P = 0.169), although overall decreased (6.28 baseline, 5.79 follow-up; global 0.48; 0.016).The results lend support four- five-factor indicate time. These data have implications for study pathophysiological mechanisms development targeted treatments symptoms.

Language: Английский

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The Brief negative Symptom Scale (BNSS): a systematic review of measurement properties

Schizophrenia, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 27, 2023

Abstract Background Negative symptoms of schizophrenia are linked with poor functioning and quality life. Therefore, appropriate measurement tools to assess negative needed. The NIMH-MATRICS Consensus defined five domains for symptoms, which Brief Symptom Scale (BNSS) covers. Methods We used the COSMIN guidelines systematic reviews evaluate psychometric data BNSS scale as a Clinician-Rated Outcome Measure (ClinROM). Results search strategy resulted in inclusion 17 articles. When using risk bias checklist, there was generally good reporting structural validity hypothesis testing. Internal consistency, reliability cross-cultural were poorer quality. ClinROM development content showed inadequate results. According updated criteria properties, validity, internal consistency interrater results, while testing Cross-cultural test-retest indeterminate. GRADE approach moderate grade. Conclusions can potentially recommend use concise tool rate symptoms. Due weaknesses certain further validations warranted.

Language: Английский

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Correlations between Negative Symptoms and Cognitive Deficits in Individuals at First Psychotic Episode or at High Risk of Psychosis: A Systematic Review

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(22), P. 7095 - 7095

Published: Nov. 14, 2023

The present review aims to identify correlations between negative symptoms (NS) and deficits in neurocognition social cognition subjects with first-episode psychosis (FEP) at-high-risk populations (HR). A systematic search of the literature published 1 January 2005 31 December 2022 was conducted on PubMed, Scopus, PsycInfo. Out 4599 records identified, a total 32 studies met our inclusion/exclusion criteria. Data 3086 FEP 1732 HR were collected. available evidence shows that NS correlate executive functioning theory mind subjects, processing speed, attention vigilance, working memory subjects. Visual learning do not either or More inconsistent findings retrieved relation other cognitive domains both samples. is limited by sample methodological heterogeneity across rated as poor average quality for majority included CHR populations. Further research based shared definitions at-risk states, well more recent conceptualizations impairment, highly needed.

Language: Английский

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External validation of the five domains of negative symptoms: Focus on cognition, functional capacity, and real-world functioning

European Psychiatry, Journal Year: 2023, Volume and Issue: 67(1)

Published: Dec. 14, 2023

The conceptualization of negative symptoms (NS) in schizophrenia is still controversial. Recent confirmatory factor-analytic studies suggested that the bi-dimensional model (motivational deficit [MAP] and expressive [EXP]) may not capture complexity NS structure, which could be better defined by a five-factor (five domains) or hierarchical domains as first-order factors, MAP EXP, second-order factors). A validation these models needed to define structure NS. To evaluate validity temporal stability brief symptom scale (BNSS) individuals with (SCZ), exploring associations between cognition, social functional capacity, functioning at baseline 4 years follow-up.

Language: Английский

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A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: April 22, 2024

Management of negative symptoms is one the most challenging and important unmet needs schizophrenia treatment. Negative together with positive result in significant psychosocial impairment poor quality life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia hypertension. A compound greater affinity for dopamine D2/D3 receptors may improve symptoms, mood, cognitive associated schizophrenia. In 2015, US FDA has approved cariprazine, a partial agonist schizophrenia, mania or mixed episodes. Midlands Lancashire Commissioning Support Unit, UK (2019) particularly suggested cariprazine predominant India’s Central Drugs Standard Control Organization (CDSCO) 2021 manic episodes bipolar I disorder. ten-fold D3 agonism serotonin receptors, along longer half-life make distinct when compared other antipsychotics. Cariprazine also have fewer incidents metabolic hormonal been shown provide better relapse prevention. Recent evidence indicates promising effect ameliorating well psychotic patients addition, improved (adjunctive/monotherapy) having inadequate response an ongoing antipsychotic clinically established. This review presents evidence-based safety efficacy

Language: Английский

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Network analysis of clinical features in patients with treatment-resistant schizophrenia

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

This study compares the clinical features of Treatment-Resistant Schizophrenia (TRS) and Non-Treatment-Resistant (NTRS) using network analysis. We recruited 511 patients, dividing them into TRS (N = 269) NTRS 242) groups. Eight scales were used: Positive Negative Syndrome Scale (PANSS), Symptom Assessment (SAPS), for Symptoms (SANS), Simpson-Angus (SAS), Abnormal Involuntary Movements (AIMS), Barnes Akathisia Rating (BARS), Calgary Depression (CDSS), Global Functioning (GAF). Demographic data analyzed T-tests Chi-square tests. Network analysis was then applied to compare features. Significant differences found in overall architectures (S 1.396, p < 0.002) edge weights (M 0.289, 0.009) networks. Nine edges (p 0.05) five nodes 0.01) differed, indicating a correlation between symptoms two core linked social functions through both positive (SAPS) negative while related general psychopathological (PANSS-G). For TRS, it is essential address symptoms, focusing on impact functioning. Additionally, managing medication side effects crucial avoid worsening symptoms.

Language: Английский

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Quality of Life of People with Schizophrenia: A Discussion Paper

Pacific Rim International Journal of Nursing Research, Journal Year: 2025, Volume and Issue: 29(2), P. 219 - 230

Published: Feb. 22, 2025

Quality of life in people with schizophrenia is a critical yet often overlooked aspect mental health care. This paper discusses the state-of-the-art quality schizophrenia, highlighting key dimensions beyond clinical aspects, including psychological well-being, social and community relationships, environmental factors. The existing research interventions focused on are also discussed to identify progress made understanding improving for this population outline future directions, nursing practice, strategies needed support their well-being further. includes examining complex factors influencing life, evaluating effectiveness current systems, proposing new approaches enhance overall persons schizophrenia.

Language: Английский

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