A new class of antipsychotics to treat schizophrenia show encouraging results

Thanks to a new mechanism of action, xanomeline-trospium is proving effective in reducing the severity of schizophrenia symptoms. Rather than blocking dopamine receptors, this treatment targets muscarinic receptors. Current antipsychotics show some efficacy in reducing the positive symptoms of schizophrenia but have limited effects on negative and cognitive symptoms. Given that 20% to 30% of patients respond partially or not at all to treatment, there is a need to offer therapeutic alternatives.The oral compound xanomeline-trospium (KarXT) showed encouraging results in a randomized, double-blind Phase 3 clinical trial (EMERGENT-3), with results published in JAMA Psychiatry in May. The trial involved 256 participants with a diagnosis of schizophrenia. For five weeks, twice a day, they received either xanomeline-trospium (maximum dose 125 mg for xanomeline and 30 mg for trospium) or placebo. Symptom measurement was based on the Positive and Negative Syndrome Scale (PANSS) for schizophrenia.Xanomeline-trospium was associated with a mean reduction of 20.6 points on the PANSS, compared with 12.2 points in the control group, a difference of 8.4 points. A reduction of at least 30% in symptoms was observed in just over 50% of participants taking KarXT. Nausea, dyspepsia, vomiting, constipation, hypertension and diarrhea were among the most frequent side effects in the clinical trial.Improved tolerabilityXanomeline is a muscarinic M1 and M4 receptor agonist. Its efficacy in reducing the psychotic symptoms of schizophrenia has been known for many years. Unfortunately, significant side-effects were an obstacle to further clinical trials. Combining the molecule with trospium chloride, a muscarinic antagonist, improved tolerability. The frequency and severity of gastrointestinal symptoms were greatly reduced.“The treatment was well tolerated, without the problematic side-effects associated with currently approved antipsychotics: extrapyramidal syndrome, weight gain, somnolence or hyperprolactinemia,” report the study authors.Improvements were noticeable as early as week 2 and continued until the end of treatment. Two 52-week clinical trials (EMERGENT-4 and EMERGENT-5) are currently underway and appear to demonstrate that long-term improvements are also possible.After one year of treatment, an interim analysis revealed that more than 75% of participants achieved at least a 30% improvement in their symptoms, with an average reduction of 33.3 points, based on the PANSS. Xanomeline-trospium continued to be well tolerated, with side-effects comparable to those observed in previous clinical trials.KarXT is currently under review by the Food and Drug Administration, which is expected to issue its decision in September.

A new class of antipsychotics to treat schizophrenia show encouraging results

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