Siafis Spyridon, McCutcheon Robert, Chiocchia Virginia, Ostinelli Edoardo G, Wright Simonne, Stansfield Claire, Juma Damian Omari, Mantas Ioannis, Howes Oliver D, Rutigliano Grazia, Ramage Fiona, Tinsdeall Francesca, Friedrich Claire, Milligan Lea, Moreno Carmen, Elliott Julian H, Thomas James, Macleod Malcolm R, Sena Emily S, Seedat Soraya, Salanti Georgia, Potts Jennifer, Cipriani Andrea, Leucht Stefan
Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany.
Department of Psychiatry, University of Oxford, Oxford, England, UK.
Wellcome Open Res. 2023 Aug 25;8:365. doi: 10.12688/wellcomeopenres.19866.1. eCollection 2023.
There is an urgent need to develop more effective and safer antipsychotics beyond dopamine 2 receptor antagonists. An emerging and promising approach is TAAR1 agonism. Therefore, we will conduct a living systematic review and meta-analysis to synthesize and triangulate the evidence from preclinical animal experiments and clinical studies on the efficacy, safety, and underlying mechanism of action of TAAR1 agonism for psychosis.
Independent searches will be conducted in multiple electronic databases to identify clinical and animal experimental studies comparing TAAR1 agonists with licensed antipsychotics or other control conditions in individuals with psychosis or animal models for psychosis, respectively. The primary outcomes will be overall psychotic symptoms and their behavioural proxies in animals. Secondary outcomes will include side effects and neurobiological measures. Two independent reviewers will conduct study selection, data extraction using predefined forms, and risk of bias assessment using suitable tools based on the study design. Ontologies will be developed to facilitate study identification and data extraction. Data from clinical and animal studies will be synthesized separately using random-effects meta-analysis if appropriate, or synthesis without meta-analysis. Study characteristics will be investigated as potential sources of heterogeneity. Confidence in the evidence for each outcome and source of evidence will be evaluated, considering the summary of the association, potential concerns regarding internal and external validity, and reporting biases. When multiple sources of evidence are available for an outcome, an overall conclusion will be drawn in a triangulation meeting involving a multidisciplinary team of experts. We plan trimonthly updates of the review, and any modifications in the protocol will be documented. The review will be co-produced by multiple stakeholders aiming to produce impactful and relevant results and bridge the gap between preclinical and clinical research on psychosis.
PROSPERO-ID: CRD42023451628.
迫切需要开发出比多巴胺2受体拮抗剂更有效、更安全的抗精神病药物。一种新兴且有前景的方法是TAAR1激动作用。因此，我们将进行一项实时系统评价和荟萃分析，以综合和梳理来自临床前动物实验及临床研究的证据，这些证据涉及TAAR1激动作用治疗精神病的疗效、安全性及潜在作用机制。
将在多个电子数据库中进行独立检索，以分别识别将TAAR1激动剂与已获许可的抗精神病药物或其他对照条件相比较的临床和动物实验研究，这些研究分别针对患有精神病的个体或精神病动物模型。主要结局将是动物的总体精神病症状及其行为替代指标。次要结局将包括副作用和神经生物学指标。两名独立的评审员将进行研究筛选，使用预定义表格提取数据，并根据研究设计使用合适的工具评估偏倚风险。将开发本体以促进研究识别和数据提取。如果合适，将使用随机效应荟萃分析分别综合临床和动物研究的数据，或在不进行荟萃分析的情况下进行综合。将研究特征作为异质性的潜在来源进行调查。将评估每个结局和证据来源的证据可信度，同时考虑关联总结、对内部和外部有效性的潜在担忧以及报告偏倚。当一个结局有多个证据来源时，将在一个由多学科专家团队参与的三角互证会议上得出总体结论。我们计划每三个月更新一次评价，并记录方案中的任何修改。该评价将由多个利益相关者共同开展，旨在产生有影响力且相关的结果，并弥合精神病临床前研究与临床研究之间的差距。
PROSPERO编号：CRD42023451628
