Bahareh Peyrovian, Lena Palaniyappan, Theodore T Kolivakis, Howard C Margolese
{"title":"精神分裂症相关认知障碍的药理学和机制干预：注册临床试验综述","authors":"Bahareh Peyrovian, Lena Palaniyappan, Theodore T Kolivakis, Howard C Margolese","doi":"10.1111/acps.70034","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is characterized by positive, negative, and cognitive symptoms. Current pharmacological treatments often fail to address cognitive deficits. In this review of clinical trials, we aim to identify studies that explore neurobiological (non-psychological) strategies to address Cognitive Impairment Associated with Schizophrenia (CIAS).</p><p><strong>Methods: </strong>A search of clinical trial databases was conducted through US National Institutes of Health's ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform (ICTRP) on August 2, 2024, with complementary searches performed on July 4 and 10, 2025, for each respective database to update the results.</p><p><strong>Results: </strong>We identified 510 relevant interventional studies that objectively measured cognitive performance. Most trials were conducted in the United States (36.4%) and focused on treatment (79%), with randomized designs (88%), investigating drugs (56%), devices (33%), and dietary supplements (10%). Of these trials, 17% reported positive pro-cognitive evidence. Glutamate modulators were the most studied drug category (63 trials), with positive results for sarcosine, BI425809 (Iclepertin), d-serine, d-cycloserine, and minocycline in small-scale trials, although the results were not replicated in larger studies. Nicotinic receptor modulators like ABT-126 and encenicline also showed some cognitive benefits. Device-based interventions, particularly rTMS and iTBS, demonstrated improvements in global cognition, working memory, attention, and processing speed in a subset of trials.</p><p><strong>Conclusion: </strong>In this comprehensive overview of clinical trials on pro-cognitive agents in schizophrenia, we identify emerging opportunities but also acknowledge a lack of replicated evidence. Despite extensive attempts to address CIAS, it remains an undertreated domain, and future trials should explore better ways to treat this important condition.</p>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":" ","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacological and Mechanistic Interventions for Cognitive Impairment Associated With Schizophrenia: A Review of Registered Clinical Trials.\",\"authors\":\"Bahareh Peyrovian, Lena Palaniyappan, Theodore T Kolivakis, Howard C Margolese\",\"doi\":\"10.1111/acps.70034\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Schizophrenia is characterized by positive, negative, and cognitive symptoms. Current pharmacological treatments often fail to address cognitive deficits. In this review of clinical trials, we aim to identify studies that explore neurobiological (non-psychological) strategies to address Cognitive Impairment Associated with Schizophrenia (CIAS).</p><p><strong>Methods: </strong>A search of clinical trial databases was conducted through US National Institutes of Health's ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform (ICTRP) on August 2, 2024, with complementary searches performed on July 4 and 10, 2025, for each respective database to update the results.</p><p><strong>Results: </strong>We identified 510 relevant interventional studies that objectively measured cognitive performance. Most trials were conducted in the United States (36.4%) and focused on treatment (79%), with randomized designs (88%), investigating drugs (56%), devices (33%), and dietary supplements (10%). Of these trials, 17% reported positive pro-cognitive evidence. Glutamate modulators were the most studied drug category (63 trials), with positive results for sarcosine, BI425809 (Iclepertin), d-serine, d-cycloserine, and minocycline in small-scale trials, although the results were not replicated in larger studies. Nicotinic receptor modulators like ABT-126 and encenicline also showed some cognitive benefits. Device-based interventions, particularly rTMS and iTBS, demonstrated improvements in global cognition, working memory, attention, and processing speed in a subset of trials.</p><p><strong>Conclusion: </strong>In this comprehensive overview of clinical trials on pro-cognitive agents in schizophrenia, we identify emerging opportunities but also acknowledge a lack of replicated evidence. 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Pharmacological and Mechanistic Interventions for Cognitive Impairment Associated With Schizophrenia: A Review of Registered Clinical Trials.
Background: Schizophrenia is characterized by positive, negative, and cognitive symptoms. Current pharmacological treatments often fail to address cognitive deficits. In this review of clinical trials, we aim to identify studies that explore neurobiological (non-psychological) strategies to address Cognitive Impairment Associated with Schizophrenia (CIAS).
Methods: A search of clinical trial databases was conducted through US National Institutes of Health's ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform (ICTRP) on August 2, 2024, with complementary searches performed on July 4 and 10, 2025, for each respective database to update the results.
Results: We identified 510 relevant interventional studies that objectively measured cognitive performance. Most trials were conducted in the United States (36.4%) and focused on treatment (79%), with randomized designs (88%), investigating drugs (56%), devices (33%), and dietary supplements (10%). Of these trials, 17% reported positive pro-cognitive evidence. Glutamate modulators were the most studied drug category (63 trials), with positive results for sarcosine, BI425809 (Iclepertin), d-serine, d-cycloserine, and minocycline in small-scale trials, although the results were not replicated in larger studies. Nicotinic receptor modulators like ABT-126 and encenicline also showed some cognitive benefits. Device-based interventions, particularly rTMS and iTBS, demonstrated improvements in global cognition, working memory, attention, and processing speed in a subset of trials.
Conclusion: In this comprehensive overview of clinical trials on pro-cognitive agents in schizophrenia, we identify emerging opportunities but also acknowledge a lack of replicated evidence. Despite extensive attempts to address CIAS, it remains an undertreated domain, and future trials should explore better ways to treat this important condition.
期刊介绍：
Acta Psychiatrica Scandinavica acts as an international forum for the dissemination of information advancing the science and practice of psychiatry. In particular we focus on communicating frontline research to clinical psychiatrists and psychiatric researchers.
Acta Psychiatrica Scandinavica has traditionally been and remains a journal focusing predominantly on clinical psychiatry, but translational psychiatry is a topic of growing importance to our readers. Therefore, the journal welcomes submission of manuscripts based on both clinical- and more translational (e.g. preclinical and epidemiological) research. When preparing manuscripts based on translational studies for submission to Acta Psychiatrica Scandinavica, the authors should place emphasis on the clinical significance of the research question and the findings. Manuscripts based solely on preclinical research (e.g. animal models) are normally not considered for publication in the Journal.
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