Cobenfy: An FDA-Approved Novel Treatment for Schizophrenia

Abstract

Schizophrenia is a chronic psychiatric disorder characterized by positive, negative, and cognitive symptoms. According to APA guidelines, antipsychotic therapy is the treatment of choice (Ramey & Silva Almodóvar, 2025). The FDA approved a novel drug called Cobenfy in September 2024, which acts on the cholinergic receptors (Smith et al., 2025). In this review, we explore the role of xanomeline-trospium chloride (Cobenfy) in the management of schizophrenia, compare efficacies with current antipsychotic treatment, and understand adverse effects and discontinuation rates. A literature search was conducted across databases such as PubMed, ScienceDirect and Cochrane Library using keywords such as “Schizophrenia”, “Cobenfy”, “Xanomeline-Trospium”, “Novel Antipsychotic”, “Pharmacotherapy”, “Psychiatric disorders”. In clinical trials so far, Cobenfy had similar outcomes in terms of PANSS (average reduction of 9.6 and 8.4 points for PS and NS, respectively) when compared with traditional antipsychotics (aripiprazole, risperidone, and olanzapine) but has a much lower risk of neuromotor and sexual effects, and weight gain (Figure 2) (Fabiano et al., 2024). It also showed an improvement in NS (such as blunted or flat affect) as per PANSS Marder Negative Factor Scores (Figure 1) (Horan et al., 2024). Additionally, it has a potential benefit for patients with residual PS and those unresponsive to antipsychotic therapy (Fabiano et al., 2024). However, Cobenfy has the highest all-cause discontinuation rate compared to risperidone (RR: 0.64) and olanzapine (RR: 0.6). Mild to moderate GI (nausea, vomiting, dyspepsia) and rare anticholinergic (constipation, urinary retention, tachycardia) adverse effects occurred with low incidence (Figure 2) (Kaul et al., 2025; Wright et al., 2024). It is associated with hepato-renal toxicity; however, its low sedation and cognitive burden may improve clinical and psychiatric assessments and reduce aggression, supporting ethical use in forensic settings without compromising autonomy (Hasan & Abid, 2024). Cobenfy represents a major development in the pharmacotherapy of schizophrenia. Although it has multiple risks, it offers advantages over conventional antipsychotics due to fewer antidopaminergic side effects. However, more RCTs are required to assess its safety and efficacy in the long term (Hasan & Abid, 2024).