Cobenfy (xanomeline-trospium chloride) for schizophrenia: A clinical update

ObjectiveTo provide Australian doctors working in psychiatry with a clinical update on xanomeline-trospium chloride (Cobenfy), the first antipsychotic approved in seven decades that acts independently of dopamine receptor binding and to consider its relevance to Australian clinical practice.ConclusionsCobenfy demonstrates efficacy in treating exacerbations of schizophrenia via muscarinic agonism with a favourable motor and metabolic adverse effect profile compared to existing antipsychotics. It has significant gastrointestinal adverse effects, strict dietary requirements, high long-term attrition, and the absence of active-comparator trial data which represent important limitations. As of March 2026, no Therapeutic Goods Administration (TGA) registration application has been submitted. However, Australian doctors working in psychiatry should familiarise themselves with the evidence base and anticipated prescribing challenges in advance of TGA review.