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Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.
To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.
This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.
The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.
This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.
Aboriginal Elders in Australia are recognised as having an important role as community leaders and cultural knowledge holders. However, the effects of colonisation and institutional racism mean Elders also experience significant social and economic disadvantage and poor health outcomes. There has been a systemic lack of attention to the worldviews and priorities of Aboriginal people as they age. In this article, we detail the findings of a qualitative study using a localised Aboriginal Elder-informed methodology that involved interviews and focus groups with 22 Aboriginal Elders in the remote town of Walgett on what ageing well means to them. This study was undertaken as part of a long-term partnership between a unique community-controlled Elders organisation and a university. The findings illuminate the barriers and enablers to ageing well for Aboriginal people in Walgett and elsewhere, and demonstrate the value to research, policy and service delivery of listening to and learning from Elders, centring Indigenous knowledges and worldviews, and bringing a more holistic conceptualisation of wellbeing to the understanding of what it means to age well.
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