Inhibiting Muscarinic Signaling with Xanomeline-Tropsium to Manage Schizophrenia
|
Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on January 31st, 2025
|
Antipsychotic medications commonly used to treat schizophrenia work by blocking dopamine receptors. However, these medications are not effective in addressing the negative symptoms of schizophrenia and are often poorly tolerated due to their adverse effects. Xanomeline-tropsium chloride is a novel antimuscarinic agent that may offer a new approach to managing schizophrenia by targeting the acetylcholine imbalance associated with the disease. A study funded by Karuna Therapeutics was conducted to investigate the potential use of Xanomeline-tropsium chloride in the treatment of schizophrenia.
The phase 3 clinical study included 256 participants with an average age of 43, all diagnosed with schizophrenia. Baseline assessment using the Positive and Negative Syndrome Scale (PANSS) revealed an average score of 97, with 30 representing healthy individuals and 210 indicating the most severe form of the disease. The breakdown of the PANSS showed a positive symptoms subscore of 26.7 out of 49, a negative symptoms subscore of 22.3 out of 49, and a general psychopathology score of 21.9 out of 112. Participants were randomly assigned to receive either a placebo or xanomeline-tropsium chloride, which was administered twice daily. For the first 2 days, the dosage consisted of 50 mg of xanomeline and 20 mg of trospium, which was then increased to 100 mg of xanomeline and 20 mg of trospium. After 5 weeks of treatment, the researchers found that the PANSS scores in the xanomeline-tropsium group decreased by an average of 20.6 points, significantly more than the 12.2-point reduction observed in the placebo group. This reduction was noted across all PANSS subscores. However, the use of xanomeline-tropsium was associated with an increased risk of side effects, particularly nausea, dyspepsia, vomiting, and constipation. The researchers recommended that future studies with longer observation periods are needed to assess the long-term sustainability of xanomeline-tropsium’s effect.
The phase 3 clinical study included 256 participants with an average age of 43, all diagnosed with schizophrenia. Baseline assessment using the Positive and Negative Syndrome Scale (PANSS) revealed an average score of 97, with 30 representing healthy individuals and 210 indicating the most severe form of the disease. The breakdown of the PANSS showed a positive symptoms subscore of 26.7 out of 49, a negative symptoms subscore of 22.3 out of 49, and a general psychopathology score of 21.9 out of 112. Participants were randomly assigned to receive either a placebo or xanomeline-tropsium chloride, which was administered twice daily. For the first 2 days, the dosage consisted of 50 mg of xanomeline and 20 mg of trospium, which was then increased to 100 mg of xanomeline and 20 mg of trospium. After 5 weeks of treatment, the researchers found that the PANSS scores in the xanomeline-tropsium group decreased by an average of 20.6 points, significantly more than the 12.2-point reduction observed in the placebo group. This reduction was noted across all PANSS subscores. However, the use of xanomeline-tropsium was associated with an increased risk of side effects, particularly nausea, dyspepsia, vomiting, and constipation. The researchers recommended that future studies with longer observation periods are needed to assess the long-term sustainability of xanomeline-tropsium’s effect.