ABSTRACT
INTRODUCTION: Schizophrenia is a mental illness that can disrupt emotions, perceptions, and cognition and reduce quality of life. The classical approach to treat schizophrenia is to use typical and atypical antipsychotics; however, limitations include low efficacy in mitigating negative symptoms and cognitive dysfunctions and a range of adverse effects. Evidence has accumulated on trace amine-associated receptor 1 (TAAR1) as a novel therapeutic target for treating schizophrenia. This systematic review investigates the available evidence on a TAAR1 agonist, ulotaront, as a treatment for schizophrenia. METHODS: A systematic search was conducted on PubMed/MEDLINE and Ovid databases for English-published articles from inception to 18 December 2022. The literature focusing on the association between ulotaront and schizophrenia was evaluated based on an inclusion/exclusion criterion. Selected studies were assessed for the risk of bias, using the Cochrane Collaboration tool, and summarized in a table to generate discussion topics. RESULTS: Three clinical, two comparative, and five preclinical studies examining ulotaront's pharmacology, tolerability and safety, and/or efficacy were identified. Results indicate that ulotaront has a differing adverse effect profile from other antipsychotics, may mitigate metabolic-related adverse effects commonly associated with antipsychotics, and may be effective for treating positive and negative symptoms. CONCLUSIONS: Findings from the available literature present ulotaront as a potential and promising alternative treatment method for schizophrenia. Despite this, our results were limited due to the lack of clinical trials on ulotaront's long-term efficacy and mechanisms of action. Future research should focus on these limitations to elucidate ulotaront's efficacy and safety for the treatment of schizophrenia and other mental disorders with similar pathophysiology.
