Wedi'i Gadw mewn:
| Prif Awdur: | |
|---|---|
| Fformat: | Recurso digital |
| Iaith: | Saesneg |
| Cyhoeddwyd: |
Zenodo
2026
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| Pynciau: | |
| Mynediad Ar-lein: | https://doi.org/10.5281/zenodo.19627308 |
| Tagiau: |
Ychwanegu Tag
Dim Tagiau, Byddwch y cyntaf i dagio'r cofnod hwn!
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Tabl Cynhwysion:
- <p><strong>Background:</strong> Xanomeline-trospium (Cobenfy), the first antipsychotic with a non-dopaminergic mechanism approved in over 30 years, received FDA approval for schizophrenia in September 2024. We characterised its post-marketing safety profile using pharmacovigilance signal detection and active-comparator analyses against six D2 antagonist antipsychotics.</p> <p><strong>Methods:</strong> We conducted a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS), Q4 2024 to Q4 2025, using a four-method battery (ROR, PRR, IC, EBGM) with consensus defined as positivity on three or more methods. Active-comparator analyses used Bonferroni-corrected ROR against olanzapine, risperidone, aripiprazole, quetiapine, lurasidone, and brexpiprazole. Time-to-onset, E-value, polypharmacy sensitivity, and disease-manifestation classification analyses were performed. Pre-registered on OSF (doi:10.17605/OSF.IO/2PWUD). Reported per READUS-PV.</p> <p><strong>Findings:</strong> Among 1,808,859 deduplicated FAERS cases, 1,423 listed xanomeline-trospium as suspect. We identified 56 consensus signals (37 pharmacological, 19 disease manifestations). Dominant signals were gastrointestinal (nausea ROR 7.5, vomiting 8.4, constipation 6.5) and muscarinic/anticholinergic (urinary retention 44.0, drooling 61.0, dry mouth 6.2). Weight gain (ROR 0.10-0.14 vs all comparators), EPS, metabolic events, and hyperprolactinaemia were significantly lower. All events were early-onset (Weibull beta < 1, median 0-3 days). E-values for 46/56 signals exceeded 3.0.</p> <p><strong>Interpretation:</strong> The post-marketing safety profile confirms the expected mechanistic trade-off: gastrointestinal and cholinergic burden in exchange for markedly reduced metabolic and extrapyramidal liability. Drooling and urinary retention warrant targeted monitoring.</p>