Ebenezer Oloyede1,2, Cecilia Casetta2,3, Olubanke Dzahini1,4, Aviv Segev2,5, Fiona Gaughran2,3, Sukhi Shergill2,3, Alek Mijovic6, Marinka Helthuis7, Eromona Whiskey1,2,3,8, James Hunter MacCabe2,3,8, David Taylor1,4. 1. Pharmacy Department, South London and Maudsley NHS Foundation Trust, London, UK. 2. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 3. National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, UK. 4. Institute of Pharmaceutical Science, King's College, London, UK. 5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 6. Kings College Hospital NHS Foundation Trust, London, UK. 7. Leyden Delta B.V., Nijmegen, The Netherlands. 8. NIHR Biomedical Research Centre for Mental Health South London and Maudsley NHS, London, UK.
Abstract
BACKGROUND AND AIMS: In the United Kingdom, patients on clozapine whose hematological parameters fall below certain thresholds are placed on the Central Non-Rechallenge Database (CNRD), meaning that they cannot be prescribed clozapine again except under exceptional circumstances. This practice was discontinued in the United States in 2015 by expanding the hematological monitoring guidelines, allowing more patients to receive clozapine. Our objective was to investigate the implications this policy change would have on clozapine utilization in the United Kingdom. METHODS: This was an observational, retrospective analysis of patients registered on the CNRD in a large mental health trust. The first objective was to compare the number of patients placed on the CNRD under the United Kingdom and the US Food and Drug Administration (FDA) criteria. The second objective was to explore the hematological and clinical outcomes of CNRD patients. The third objective was to investigate the hematological outcomes of patients rechallenged on clozapine after nonrechallengeable status. RESULTS: One hundred and fifteen patients were placed on CNRD from 2002 to 2019, of whom 7 (6%) met the equivalent criteria for clozapine discontinuation under the FDA guidelines. Clinical outcomes, as measured by the Clinical Global Impression-Severity scale, were worse 3 months after clozapine cessation than on clozapine (t = -7.4862; P < .001). Sixty-two (54%) patients placed on CNRD were rechallenged. Fifty-nine of those (95%) were successfully rechallenged; 3 patients were placed back on CNRD, only one of which would have had to stop clozapine again under FDA criteria. CONCLUSION: Implementation of the updated FDA's monitoring criteria in the United Kingdom would significantly reduce clozapine discontinuation due to hematological reasons. The evidence suggests an urgent need for revising the UK clozapine monitoring guidelines to improve outcomes in treatment-resistant schizophrenia.
BACKGROUND AND AIMS: In the United Kingdom, patients on clozapine whose hematological parameters fall below certain thresholds are placed on the Central Non-Rechallenge Database (CNRD), meaning that they cannot be prescribed clozapine again except under exceptional circumstances. This practice was discontinued in the United States in 2015 by expanding the hematological monitoring guidelines, allowing more patients to receive clozapine. Our objective was to investigate the implications this policy change would have on clozapine utilization in the United Kingdom. METHODS: This was an observational, retrospective analysis of patients registered on the CNRD in a large mental health trust. The first objective was to compare the number of patients placed on the CNRD under the United Kingdom and the US Food and Drug Administration (FDA) criteria. The second objective was to explore the hematological and clinical outcomes of CNRD patients. The third objective was to investigate the hematological outcomes of patients rechallenged on clozapine after nonrechallengeable status. RESULTS: One hundred and fifteen patients were placed on CNRD from 2002 to 2019, of whom 7 (6%) met the equivalent criteria for clozapine discontinuation under the FDA guidelines. Clinical outcomes, as measured by the Clinical Global Impression-Severity scale, were worse 3 months after clozapine cessation than on clozapine (t = -7.4862; P < .001). Sixty-two (54%) patients placed on CNRD were rechallenged. Fifty-nine of those (95%) were successfully rechallenged; 3 patients were placed back on CNRD, only one of which would have had to stop clozapine again under FDA criteria. CONCLUSION: Implementation of the updated FDA's monitoring criteria in the United Kingdom would significantly reduce clozapine discontinuation due to hematological reasons. The evidence suggests an urgent need for revising the UK clozapine monitoring guidelines to improve outcomes in treatment-resistant schizophrenia.
Authors: Jimmi Nielsen; Corina Young; Petru Ifteni; Taishiro Kishimoto; Yu-Tao Xiang; Peter F J Schulte; Christoph U Correll; David Taylor Journal: CNS Drugs Date: 2016-02 Impact factor: 5.749
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