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; ... (2023). Trace amine-associated receptor 1 (TAAR1) agonists for psychosis: protocol for a living systematic review and meta-analysis of human and non-human studies. Wellcome open research, 8(365) Wellcome Trust 10.12688/wellcomeopenres.19866.1
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BACKGROUND
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.
METHODS
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.
PROTOCOL REGISTRATION
PROSPERO-ID: CRD42023451628.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM) |
UniBE Contributor: |
Chiocchia, Virginia, Salanti, Georgia |
Subjects: |
600 Technology > 610 Medicine & health 300 Social sciences, sociology & anthropology > 360 Social problems & social services |
ISSN: |
2398-502X |
Publisher: |
Wellcome Trust |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
18 Apr 2024 15:43 |
Last Modified: |
18 Apr 2024 15:53 |
Publisher DOI: |
10.12688/wellcomeopenres.19866.1 |
PubMed ID: |
38634067 |
Uncontrolled Keywords: |
GALENOS; antipsychotic; neurotransmitters; pathophysiology; glutamate; schizophrenia; serotonin |
BORIS DOI: |
10.48350/196080 |
URI: |
https://boris.unibe.ch/id/eprint/196080 |
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