FDA Approves First Antipsychotic Medication Targeting Cholinergic Receptors for Patients with Schizophrenia
The FDA approved the first oral, antipsychotic medication—xanomeline and trospium chloride— to treat schizophrenia for adults. The xanomeline and trospium chloride capsules target cholinergic receptors instead of dopamine receptors, which is the usual standard of care for this patient population.
About 1% of Americans have schizophrenia, and it is one of the 15 leading causes of disability globally, according to the National Institute of Mental Health. People with schizophrenia are at a heightened risk of early death, and nearly 5% die by suicide.
“Schizophrenia…is a severe, chronic mental illness that is often damaging to a person’s quality of life,” Tiffany Farchione MD, director of the Division of Psychiatry, Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release. “This drug takes the first new approach to schizophrenia treatment in decades. This approval offers a new alternative to the antipsychotic medications people with schizophrenia have previously been prescribed.”
The medication’s efficacy was assessed in two identical 5-week, randomized, double-blind, placebo-controlled, multi-center studies. Participants included adults who met the DSM-5 criteria for a schizophrenia diagnosis. The researchers measured its effectiveness using the Positive and Negative Syndrome Scale (PANSS), which is a 30-item scale that quantifies symptoms of schizophrenia using a 7-point system. In both studies, participants who received the xanomeline and trospium chloride capsules experienced a “meaningful reduction” in symptoms in the PANSS total score from baseline to week 5, according to the press release.
The most common adverse effects associated with the drug are nausea, indigestion, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease.
The prescribing information warns that xanomeline and trospium chloride can cause urinary retention, increased heart rate, decreased gastric movement, or angioedema of the face and lips. It is not recommended for patients with mild hepatic impairment and should not be used in patients with known hepatic impairment. It was recommended that patients should stop using the capsules if they are experiencing symptoms of substantial liver disease, including yellowing of the skin or the white part of the eyes, dark urine, and unexplained itching. Xanomeline and trospium chloride are substantially excreted by the kidney and are not recommended for patients with moderate to severe renal impairment.
Due to these risks, it should not be prescribed to patients with urinary retention, moderate or severe kidney or liver disease, gastric retention, untreated narrow-angle glaucoma, or a history of hypersensitivity to xanomeline and trospium chloride or their components.
Reference:
FDA approves drug with new mechanism of action for treatment of schizophrenia. News release. US Food and Drug Administration; September 26, 2024. Accessed September 27, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia