Xanomeline-Trospium in Schizophrenia Resource Center

Xanomeline-trospium is the first muscarinic-based therapy approved by the FDA for schizophrenia. It combines M1 and M4 receptor agonism with peripheral muscarinic antagonism from trospium, which does not cross the blood-brain barrier. It was studied as monotherapy in the EMERGENT program and is dosed twice daily on an empty stomach.

This resource center collects the peer-reviewed publications on the subject alongside the companion material built from them: editorial articles on initiation, inpatient use and switching; a clinical pearl covering the Phase 4 SWITCH trial; the foundational papers as published abstracts; and expert video and webinar content.

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Editorial Article

Inpatient Initiation and Rapid Titration

Escalation to 100/20 or 125/30 mg by day 2 or 3, a retrospective analysis of 49 hospitalized patients, combination use with atypical antipsychotics, and discharge planning.

Editorial Article

Switching and Cross-Titration by Antipsychotic Class

Taper timelines for the -dones, -pines and -azoles, combination use with atypical antipsychotics, and long-acting injectable considerations.

Clinical Pearls

Switching From Oral Atypical Antipsychotics to Xanomeline-Trospium

The Phase 4 SWITCH trial: 105 clinically stable outpatients randomized to a 2-week or 4-week taper of their prior antipsychotic, with 8-week discontinuation, PANSS change and adverse events, alongside the expert panel's taper recommendations by drug class.

Original Research

Systematic literature review of schizophrenia clinical practice guidelines on acute and maintenance management with antipsychotics

Correll et al. · Schizophrenia, 2022

Original Research

The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia

Keepers et al. · The American Journal of Psychiatry, 2020

Original Research

The evidence for illness progression after relapse in schizophrenia

Emsley et al. · Schizophrenia Research, 2013

Expert Video

TMS for Depression: Response Rates, Protocols, and the SAINT Question

Transcranial magnetic stimulation for major depressive disorder: response and remission rates including the NeuroStar Outcomes Registry, candidacy and contraindications, 10 Hz rTMS and intermittent theta burst protocols, and the SAINT protocol and its fMRI-guided targeting.

Expert Reel 9:16

COMP360 Psilocybin in Chronic Suicidal Ideation: Reported MSSI Outcomes

A two-speaker cut covering the design of an open-label COMP360 psilocybin trial in chronic suicidal ideation and the reported MSSI change and effect sizes at weeks 1, 3 and 12.

Expert Reel 9:16

TMS Response Rates in Depression

A 9:16 cut covering the reported response rate to TMS in depression and how response is defined on the PHQ-9 and MADRS.

Webinar

A Novel Psychedelic-Based Therapeutic for Postpartum Depression: Phase 2a Results of Inhaled Mebufotenin (GH001)

Kristina Deligiannidis presents a Phase 2a single-arm, open-label trial of inhaled mebufotenin in 10 women with postpartum depression: MADRS and maternal functioning outcomes, breast milk pharmacokinetics, safety, and the stated limitations, followed by audience Q and A.

Consensus Panel Report

Real-World Implementation of Xanomeline-Trospium in Schizophrenia: A Consensus Panel Report

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.