{"title":"Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments.","authors":"Yuki Komatsu, Moe Takehara, Xenia Hart, Yuna Takahashi, Satoko Hori, Fumihiko Ueno, Hiroyuki Uchida","doi":"10.1055/a-2307-6484","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents.</p><p><strong>Methods: </strong>A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases.</p><p><strong>Results: </strong>Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.</p><p><strong>Discussion: </strong>Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacopsychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1055/a-2307-6484","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents.
Methods: A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases.
Results: Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.
Discussion: Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.
导言：传统的抗精神病药物可减轻多巴胺能神经传递，但对大约三分之一的精神分裂症患者无效。因此有必要开发非多巴胺能药物：方法：利用美国临床试验注册中心和欧盟临床试验注册中心，对已完成的精神分裂症治疗化合物 II 期和 III 期试验进行了系统检索。在最新的II期和III期试验中，在主要结果指标上明显优于安慰剂的化合物被确定下来。通过人工搜索PubMed和新闻稿，收集了所纳入化合物的相关信息：结果：共确定了16种化合物，其中4种化合物（乌洛他隆、沙诺美林/氯化曲塞膦、伐比卡西林和罗鲁哌酮）作为单一疗法进行了研究，其余12种化合物（匹马万塞林、比托哌汀、BI 425809、安塞尼可林、托吡司琼、孕烯醇酮、D-丝氨酸、雌二醇、托卡朋、伐昔洛韦、大麻二酚和利莫那班）作为附加疗法进行了研究。与安慰剂相比，乌洛他隆、沙诺美林/氯化曲安奈德、伐比卡西林、比托泊汀、雌二醇、大麻二酚、利莫那班和D-丝氨酸对阳性症状有疗效；罗哌利酮和匹马万赛林对阴性症状有效；安可奈林、托吡司琼、孕烯诺龙、托卡朋、BI 425809和伐昔洛韦改善了认知功能：讨论：功能不同于现有抗精神病药物的化合物可为精神分裂症患者提供新的症状特异性治疗策略。
期刊介绍：
Covering advances in the fi eld of psychotropic drugs, Pharmaco psychiatry provides psychiatrists, neuroscientists and clinicians with key clinical insights and describes new avenues of research and treatment. The pharmacological and neurobiological bases of psychiatric disorders are discussed by presenting clinical and experimental research.
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