Xanomeline-trospium: defining its place among the current antipsychotic landscape

Progress in the development of new and improved medications for psychosis has been notably slow and disappointing. The first treatment for schizophrenia was introduced in early 1950s and the majority of medications available today exclusively function through dopamine antagonism. The search for a new drug treatment with a different mechanism of action was extremely slow-paced mainly due to the limited understanding of the aetiology, pathophysiology and genetics of schizophrenia. Given the fact that a third of people do not respond to dopamine antagonists, there is a clear need for an antipsychotic with a different mechanism of action. In 2024, FDA approved a new medication for psychosis branded as Cobenfy. This xanomeline-trospium combination works via cholinergic pathway and the dual M1 and M4 receptor activation helps regulates dopaminergic and glutaminergic neurotransmission as well, thereby restoring balance in these circuits. Acetylcholine also helps improve cognitive processing including attention, learning and sensory gating. In this article, we try to understand the place of this unique drug in the antipsychotic ladder. We also explore the clinical scenarios where this medication can be effective as well as the potential future outlook when it comes to the treatment of schizophrenia.