{"title":"KarXT 对急性精神分裂症阴性症状的疗效:对三项试验的汇总数据进行事后分析","authors":"","doi":"10.1016/j.schres.2024.08.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Currently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M<sub>1</sub> /M<sub>4</sub> preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms.</p></div><div><h3>Methods</h3><p>Data were pooled from the three pivotal trials of KarXT monotherapy in people with schizophrenia with an acute exacerbation of psychosis. All 3 studies used similar 5-week randomized, double-blind, placebo-controlled designs (modified intention-to-treat sample <em>N</em> = 640). PANSS criteria proposed in the literature identified a subset of study participants (<em>n</em> = 64) with prominent NS.</p></div><div><h3>Results</h3><p>KarXT was significantly better than placebo on PANSS Marder Negative Factor Scores in the full sample (<em>p</em> < .001; Cohen's d = 0.42) and more so in the prominent NS subgroup (p < .001; Cohen's d = 1.18). Further, the KarXT effect in the NS subgroup remained significant after accounting for changes in positive symptoms, depression/anxiety, disorganization, and hostility.</p></div><div><h3>Conclusions</h3><p>Participants with prominent NS revealed greater improvement of NS following KarXT therapy than the full sample that persisted after accounting for positive and other symptoms. While these findings must be interpreted with caution, they are consistent with the possibility that NS improvements associated with KarXT are not secondary to improvements in other symptom domains and support further investigation in larger, stable outpatient studies.</p></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0920996424003724/pdfft?md5=d1aa8cc4d77e56e17731c26655a7f49c&pid=1-s2.0-S0920996424003724-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials\",\"authors\":\"\",\"doi\":\"10.1016/j.schres.2024.08.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Currently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M<sub>1</sub> /M<sub>4</sub> preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms.</p></div><div><h3>Methods</h3><p>Data were pooled from the three pivotal trials of KarXT monotherapy in people with schizophrenia with an acute exacerbation of psychosis. All 3 studies used similar 5-week randomized, double-blind, placebo-controlled designs (modified intention-to-treat sample <em>N</em> = 640). PANSS criteria proposed in the literature identified a subset of study participants (<em>n</em> = 64) with prominent NS.</p></div><div><h3>Results</h3><p>KarXT was significantly better than placebo on PANSS Marder Negative Factor Scores in the full sample (<em>p</em> < .001; Cohen's d = 0.42) and more so in the prominent NS subgroup (p < .001; Cohen's d = 1.18). Further, the KarXT effect in the NS subgroup remained significant after accounting for changes in positive symptoms, depression/anxiety, disorganization, and hostility.</p></div><div><h3>Conclusions</h3><p>Participants with prominent NS revealed greater improvement of NS following KarXT therapy than the full sample that persisted after accounting for positive and other symptoms. While these findings must be interpreted with caution, they are consistent with the possibility that NS improvements associated with KarXT are not secondary to improvements in other symptom domains and support further investigation in larger, stable outpatient studies.</p></div>\",\"PeriodicalId\":21417,\"journal\":{\"name\":\"Schizophrenia Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0920996424003724/pdfft?md5=d1aa8cc4d77e56e17731c26655a7f49c&pid=1-s2.0-S0920996424003724-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Schizophrenia Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0920996424003724\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Schizophrenia Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0920996424003724","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials
Background
Currently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M1 /M4 preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms.
Methods
Data were pooled from the three pivotal trials of KarXT monotherapy in people with schizophrenia with an acute exacerbation of psychosis. All 3 studies used similar 5-week randomized, double-blind, placebo-controlled designs (modified intention-to-treat sample N = 640). PANSS criteria proposed in the literature identified a subset of study participants (n = 64) with prominent NS.
Results
KarXT was significantly better than placebo on PANSS Marder Negative Factor Scores in the full sample (p < .001; Cohen's d = 0.42) and more so in the prominent NS subgroup (p < .001; Cohen's d = 1.18). Further, the KarXT effect in the NS subgroup remained significant after accounting for changes in positive symptoms, depression/anxiety, disorganization, and hostility.
Conclusions
Participants with prominent NS revealed greater improvement of NS following KarXT therapy than the full sample that persisted after accounting for positive and other symptoms. While these findings must be interpreted with caution, they are consistent with the possibility that NS improvements associated with KarXT are not secondary to improvements in other symptom domains and support further investigation in larger, stable outpatient studies.
期刊介绍:
As official journal of the Schizophrenia International Research Society (SIRS) Schizophrenia Research is THE journal of choice for international researchers and clinicians to share their work with the global schizophrenia research community. More than 6000 institutes have online or print (or both) access to this journal - the largest specialist journal in the field, with the largest readership!
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The journal publishes novel papers that really contribute to understanding the biology and treatment of schizophrenic disorders; Schizophrenia Research brings together biological, clinical and psychological research in order to stimulate the synthesis of findings from all disciplines involved in improving patient outcomes in schizophrenia.