The research behind this topic

Abstract

Xanomeline-trospium (XT) is the first muscarinic-based therapy approved for schizophrenia. It combines M1 and M4 receptor agonism with peripheral antagonism to limit cholinergic side effects. By modulating circuits upstream of dopamine release, XT offers a mechanism that differs from traditional antipsychotics and may address positive, negative, and cognitive symptoms. In July 2025, a consensus panel of clinicians with expertise in treating schizophrenia and real-world experience using XT convened to discuss practical strategies for its use across treatment settings. The panel concluded that XT should be considered early in the course of illness, particularly in first-episode psychosis, because it may alter long-term outcomes while reducing reliance on high-dose dopamine antagonists. Outpatient strategies emphasize individualized titration and proactive management of gastrointestinal side effects to support adherence. Inpatient use allows for more rapid titration and has shown rapid benefits in both positive and negative symptoms, facilitating earlier stabilization and discharge. Cross-titration experience suggests that XT can be dose-sparing when combined with dopamine blockers, reducing the burden of metabolic and motor side effects. These real-world insights highlight XT as a versatile treatment option that expands the therapeutic possibilities for schizophrenia.

Abstract

Clinical practice guidelines (CPGs) translate evidence into recommendations to improve patient care and outcomes. To provide an overview of schizophrenia CPGs, we conducted a systematic literature review of English-language CPGs and synthesized current recommendations for the acute and maintenance management with antipsychotics. Searches for schizophrenia CPGs were conducted in MEDLINE/Embase from 1/1/2004 to 12/19/2019 and in guideline websites until 06/01/2020. Of 19 CPGs, 17 (89.5%) commented on first-episode schizophrenia (FES), with all recommending antipsychotic monotherapy, but without agreement on preferred antipsychotic. Of 18 CPGs commenting on maintenance therapy, 10 (55.6%) made no recommendations on the appropriate maximum duration of maintenance therapy, noting instead individualization of care. Eighteen (94.7%) CPGs commented on long-acting injectable antipsychotics (LAIs), mainly in cases of nonadherence (77.8%), maintenance care (72.2%), or patient preference (66.7%), with 5 (27.8%) CPGs recommending LAIs for FES. For treatment-resistant schizophrenia, 15/15 CPGs recommended clozapine. Only 7/19 (38.8%) CPGs included a treatment algorithm.

Abstract

It has long been suspected that relapse in schizophrenia is associated with disease progression in so far as time to response is longer, negative and other symptoms persist, some patients become treatment refractory and neuroprogression in terms of structural brain changes may occur. This article examines the evidence for illness progression after relapse in patients with schizophrenia. It reports on indirect evidence obtained from retrospective, naturalistic and brain-imaging studies, as well as a few prospective studies examining pre- and post-relapse treatment response. Findings suggest that the treatment response after relapse is variable, with many patients responding rapidly, others exhibiting protracted impairment of response and a subgroup displaying emergent refractoriness. This subgroup comprises about 1 in 6 patients, irrespective of whether it is the first or a subsequent relapse, and even when the delay between onset of first symptoms of relapse and initiation of treatment is brief. While there is a lack of well-designed studies investigating the post-relapse treatment outcome, available evidence gives sufficient cause for concern that, in addition to the considerable psychosocial risks, an additional risk of biological harm may be associated with relapse.