Trace amine-associated receptor 1 (TAAR1) agonists for psychosis: protocol for a living systematic review and meta-analysis of human and non-human studies.

Journal: Wellcome open research

Volume: 8

Issue: 

Year of Publication: 

Affiliated Institutions:  Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany. Department of Psychiatry, University of Oxford, Oxford, England, UK. Institute of Social and Preventive Medicine, University of Bern, Bern, Canton of Bern, Switzerland. Department of Psychiatry, Stellenbosch University, Stellenbosch, Western Cape, South Africa. EPPI Centre, Social Research Institute, University College London, London, England, UK. My Mind Our Humanity, Mombasa, Kenya. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England, UK. Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, England, UK. Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, Scotland, UK. MQ Mental Health Research, London, UK. Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, ISCIII, School of Medicine, Universidad Complutense de Madrid, Madrid, Community of Madrid, Spain. Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia.

Abstract summary 

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.

Authors & Co-authors:  Siafis Spyridon S McCutcheon Robert R Chiocchia Virginia V Ostinelli Edoardo G EG Wright Simonne S Stansfield Claire C Juma Damian Omari DO Mantas Ioannis I Howes Oliver D OD Rutigliano Grazia G Ramage Fiona F Tinsdeall Francesca F Friedrich Claire C Milligan Lea L Moreno Carmen C Elliott Julian H JH Thomas James J Macleod Malcolm R MR Sena Emily S ES Seedat Soraya S Salanti Georgia G Potts Jennifer J Cipriani Andrea A Leucht Stefan S

Study Outcome 

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Statistics
Citations :  GBD 2019 Diseases and Injuries Collaborators: Global burden of 369 diseases and injuries in 204 countries and territories, 1990– 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–22. 10.1016/S0140-6736(20)30925-9
Authors :  25
Identifiers
Doi : 365
SSN : 2398-502X
Study Population
Male,Female
Mesh Terms
Other Terms
GALENOS; antipsychotic; neurotransmitters; pathophysiology; glutamate; schizophrenia; serotonin
Study Design
Study Approach
Systemic Review
Country of Study
Publication Country
England