Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 25:8:365.
doi: 10.12688/wellcomeopenres.19866.1. eCollection 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

Spyridon Siafis  1 , Robert McCutcheon  2   3   4 , Virginia Chiocchia  5 , Edoardo G Ostinelli  2   3   6 , Simonne Wright  7 , Claire Stansfield  8 , Damian Omari Juma  9 , Ioannis Mantas  10 , Oliver D Howes  4 , Grazia Rutigliano  11 , Fiona Ramage  12 , Francesca Tinsdeall  12 , Claire Friedrich  2   6 , Lea Milligan  13 , Carmen Moreno  14 , Julian H Elliott  15   16 , James Thomas  8 , Malcolm R Macleod  12 , Emily S Sena  12 , Soraya Seedat  7 , Georgia Salanti  5 , Jennifer Potts  2   6 , Andrea Cipriani  2   3   6 , Stefan Leucht  1 ; GALENOS team
Affiliations

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

Spyridon Siafis et al. Wellcome Open Res. .

Abstract

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.

Keywords: GALENOS; antipsychotic; neurotransmitters; pathophysiology; glutamate; schizophrenia; serotonin.

PubMed Disclaimer

Conflict of interest statement

Competing interests: Spyridon Siafis: None Robert McCutcheon: RM received speaker/consultancy fees from Karuna, Janssen, Boehringer Ingelheim and Otsuka, and is director of a company that hosts psychotropic prescribing decision tools. Virginia Chiocchia: None. Edoardo G. Ostinelli: EGO has received research and consultancy fees from Angelini Pharma. Simonne Wright: None. Claire Stansfield: None. Damian Omari Juma: None. Ioannis Mantas: None. Oliver D. Howes: ODH is a part-time employee of H. Lundbeck A/S and has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organized by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Jansenn, Lundbeck, Neurocrine, Otsuka, Sunovion, Rand, Recordati, Roche and Viatris/Mylan. Neither Howes or his family have holdings/a financial stake in any pharmaceutical company Grazia Rutigliano: None. Fiona Ramage: None. Francesca Tinsdeall: None. Claire Friedrich: None. Lea Milligan: None. Carmen Moreno: CM received honoraria as a consultant and/or advisor and/or for lectures from Angelini, Compass, Esteve, Exeltis Janssen, Lundbeck, Neuraxpharm, Nuvelution, Otsuka, Pfizer, Servier and Sunovion outside the submitted work. Julian H Elliott: None. James Thomas: None. Emily Sena: None. Malcolm R. MacLeod: None. Soraya Seedat: None Georgia Salanti: None. Jennifer Potts: None. Andrea Cipriani: AC received research, educational and consultancy fees from the Italian Network for Paediatric Trials, CARIPLO Foundation, Lundbeck, and Angelini Pharma. Stefan Leucht: SL has received honoraria as advisor and/or for lectures and/or for educational material from Alkermes, Angelini, Apsen, Eisai, Gedeon Richter, Janssen, Karuna, Kynexis, Lundbeck, Medichem, Medscape, Merck Sharpp and Dome, Mitshubishi, Neurotorium, NovoNordisk, Otsuka, Recordati, Roche, Rovi, Sanofi Aventis, TEVA

Figures

Figure 1.
Figure 1.. Flow diagram of the living systematic review and protocol.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. 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 - DOI - PMC - PubMed
    1. Huhn M, Nikolakopoulou A, Schneider-Thoma J, et al. : Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019;394(10202):939–951. 10.1016/S0140-6736(19)31135-3 - DOI - PMC - PubMed
    1. Schneider-Thoma J, Chalkou K, Dörries C, et al. : Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis. Lancet. 2022;399(10327):824–836. 10.1016/S0140-6736(21)01997-8 - DOI - PubMed
    1. Kane JM, Agid O, Baldwin ML, et al. : Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia. J Clin Psychiatry. 2019;80(2): 18com12123. 10.4088/JCP.18com12123 - DOI - PubMed
    1. Spark DL, Fornito A, Langmead CJ, et al. : Beyond antipsychotics: a twenty-first century update for preclinical development of schizophrenia therapeutics. Transl Psychiatry. 2022;12(1): 147. 10.1038/s41398-022-01904-2 - DOI - PMC - PubMed