Triangulating evidence from the GALENOS living systematic review on trace amine-associated receptor 1 (TAAR1) agonists in psychosis

作者：Katharine Smith, Niall Boyce, Astrid Chevance, Virginia Chiocchia, Christoph U. Correll, Kim Donoghue, Nikita Ghodke, Tatenda Kambeu, Gin S. Malhi, Malcolm Macleod, Lea Milligan, Jamie Morgan, Jennifer Potts, Emma Robinson, Spyridon Siafis, I. Sommer, Bernhard Voelkl, Georgia Salanti, Andrea Cipriani, Julian P. T. Higgins · 发表于：The British Journal of Psychiatry · 年份：2024 · DOI：10.1192/bjp.2024.237 · 被引用次数：10 · 研究领域：Neurotransmitter Receptor Influence on Behavior、Tryptophan and brain disorders、Stress Responses and Cortisol

Background 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. Aims 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. Method 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. Results 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 d...