Year: 2025
Type: article
Abstract: There remains no approved medication treatment for the often-disabling negative symptoms of schizophrenia. The drug formulation KarXT (recently approved by the FDA as the brand name Cobenfy), a combination of the muscarinic receptor agonist xanomeline and the muscarinic receptor antagonist trospium chloride, has shown promise in three 5-week trials in patients with schizophrenia, but it is difficult to assess medication effects on negative symptoms that occur independently of improvement in positive symptoms. Investigators conducted a post hoc analysis of these trials to examine the effects of KarXT on negative symptoms in patients who did not have prominent positive symptoms. The three trials included one Phase 2 and two Phase 3 trials that enrolled adults aged 18 to 65 with a primary diagnosis of schizophrenia, a total score of at least 80 on the Positive and Negative Syndrome Scale (PANSS), and a score of at least 4 on the Clinical Global Impressions-Severity scale. From this group, the investigators for the post hoc analysis used PANSS results to identify a subgroup with prominent negative symptoms but no predominant positive symptoms at baseline. They assessed change in negative symptoms using the PANSS Marder Negative Factor model, and also examined PANSS negative symptom subcomponent scores measuring reduced emotional experience and reduced emotional expression. Among the three trials, 64 participants had prominent negative and non-predominant positive symptoms. The 29 participants in this group who received KarXT showed significantly greater improvement in negative symptoms at week 5 compared with the 35 participants who received placebo. At week 5, 50% of the KarXT group achieved at least a 30% improvement in negative symptoms, compared with 9% of the placebo group. “The magnitude of the treatment effect in this prominent [negative symptom] subgroup was nearly three times larger than the medium effect size for [negative symptoms] seen in the full sample, and further analyses showed that the KarXT effect on [negative symptoms] was largely independent of improvements in positive symptoms, disorganization, depression/anxiety, and hostility,” authors of the analysis wrote. They pointed out that the results should be interpreted with caution, in part because of the relatively small sample size in the analysis. [Horan, W., et al. (2024). Schizophr Res. https://doi.org/10.1016/j.schres.2024.08.001] Update The Food and Drug Administration (FDA) on Feb. 24 announced that it no longer expects prescribers, pharmacies, and patients to participate in the risk evaluation and mitigation strategies (REMS) program for the antipsychotic clozapine, as the federal agency takes formal steps to eliminate the clozapine REMS. The FDA is still recommending that prescribers monitor patients' absolute neutrophil count (ANC) according to monitoring frequencies cited in the prescribing information for clozapine. However, prescribers no longer are required to report results of blood tests prior to the dispensing of clozapine. “Although the risk of severe neutropenia with clozapine still exists, FDA has determined that the REMS program for clozapine is no longer necessary to ensure the benefits of the medicine outweigh that risk,” the FDA's Information on Clozapine update reads. Clozapine manufacturers have submitted documentation to eliminate their REMS efforts, and the FDA is expected to eliminate the REMS and issue updated prescribing information for clozapine in the next few months. [https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-clozapine]
DOI: 10.1002/pu.31318
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4409944685