Efficacy of xanomeline and xanomeline trospium in the treatment of cognitive impairment: A systematic review of preclinical and clinical trials
Bibliographic record
Abstract
The high prevalence, persistence and clinical burden of cognitive impairment on health outcomes in persons with schizophrenia and bipolar disorder invites the need for innovative, mechanistically informed pharmacotherapeutic interventions. Evidence implicates dysregulation of muscarinic signalling as a mediator of cognitive dysfunction, identifying it as a potential therapeutic target. In accordance with the PRISMA guidelines, a systematic search was performed using the following electronic databases: PubMed, Medline, Cochrane Library, PsycInfo, Embase, Scopus, and Web of Science. Databases were searched from inception to May 1, 2025. Study screening and selection was performed by three reviewers (K.V., B.S., and B.W.). Included studies reported on the effects of xanomeline and/or xanomeline trospium on cognitive function. A total of 24 studies were included in this review. Preclinical and clinical studies consistently demonstrate that xanomeline trospium is well tolerated in both short and long-term evaluations. Furthermore, xanomeline trospium has been associated with cognitive improvements in both animal models and clinical populations (e.g., Alzheimer's disease (AD), schizophrenia), including improvements in verbal learning, delayed memory, and reaction time. Xanomeline trospium, an FDA approved muscarinic M1/M4 partial agonist with demonstrated safety, tolerability, and efficacy, represents a novel pharmacological intervention for the treatment of schizophrenia. The convergence of preclinical and clinical findings supports the hypothesis that xanomeline trospium exerts direct pro cognitive effects in persons with schizophrenia, bipolar disorder, and potentially other neuropsychiatric conditions (e.g., AD). Limitations of the current study include limited indications investigated and the absence of a comprehensive analysis of xanomeline's overall neurobiologic effects.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.019 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.008 |
| Bibliometrics | 0.008 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".