ArticleFrontiers in psychiatry2025
Managing treatment-resistant schizophrenia following clozapine cessation: a case report of xanomeline-trospium and olanzapine combination therapy.
Article in Frontiers in psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Commentary: Real-world effectiveness and safety of xanomeline and trospium for treatment-resistant schizophrenia in a state hospital system.Frontiers in psychiatry · 2026Article
- Adjunctive xanomeline/trospium in clozapine-resistant schizophrenia: two case reports demonstrating limited response.Therapeutic advances in psychopharmacology · 2026Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Clozapine is the gold standard for treatment-resistant schizophrenia (TRS) but is limited by rare, serious adverse events. Venous thromboembolism (VTE) and pulmonary embolism (PE) represent particularly challenging complications given their multifactorial pathophysiology, unpredictable recurrence risk, and lack of clear guidance on rechallenge. Case presentation: A 44-year-old man with TRS and comorbid seizure disorder achieved over 25 years of remission on clozapine (300 mg/day). In November 2023, he developed acute deep vein thrombosis and PE, leading to permanent discontinuation despite long-term tolerability and the absence of conventional risk factors. Abrupt cessation was followed by rapid relapse. Aripiprazole, titrated to 15 mg/day, and subsequent augmentation with olanzapine failed to restore stability. A muscarinic-dopaminergic approach using xanomeline-trospium (Cobenfy™) with olanzapine was initiated, producing marked improvements in positive symptoms, affective expressivity, social engagement, and daily functioning without significant adverse effects. Discussion: Most clozapine-related VTE/PE cases necessitate discontinuation, though rare continuations under anticoagulation and multidisciplinary oversight have been described. Reviews emphasize inconclusive evidence and the need for individualized risk-benefit assessment. In this case, discontinuation was chosen collaboratively with the family, prompting exploration of alternative mechanisms. Conclusion: Clozapine-related VTE/PE represents a serious clinical dilemma. This case illustrates the potential of muscarinic-dopaminergic strategies to restore stability in TRS when clozapine is no longer an option.
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