Steffi Malik1, John Lally2, Olesya Ajnakina3, Megan Pritchard4, Amir Krivoy5, Fiona Gaughran5, Hitesh Shetty4, Robert J Flanagan3, James H MacCabe5. 1. Department of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Medical School, University of Bristol, Senate House, Tyndall Ave, Bristol, UK. Electronic address: sm15121@my.bristol.ac.uk. 2. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland; Department of Psychiatry, School of Medicine and Medical Sciences, University College Dublin, St Vincent's University Hospital, Dublin, Ireland. Electronic address: john.lally@kcl.ac.uk. 3. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. 4. BRC Case Register, South London and Maudsley NHS Foundation Trust, London, UK. 5. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, UK.
Abstract
BACKGROUND: The use of clozapine is limited due to the occurrence of neutropenia, and the rare but life threatening adverse event of agranulocytosis. There is little epidemiological research into clinical factors that may impact on this risk. We conducted a case control study examining the clinical risk factors for neutropenia patients treated with clozapine. METHOD: A case-control study was conducted within a database of anonymised electronic clinical records. All patients who discontinued clozapine due to a neutropenic event were included as cases. Matched controls were selected from patients with a documented clozapine exposure at the time of the clozapine neutropenic event of the case patient, matched by duration of clozapine treatment. RESULTS: 136 cases and 136 controls were included. In multivariable analysis, the concurrent use of sodium valproate was associated with neutropenia (Odds Raito (OR) 2.28, 95%CI: 1.27-4.11, p=0.006). There was a dose-response effect, with greater associations for higher doses. Patients who discontinued clozapine due to neutropenia were more likely to be of black ethnicity (OR 2.99, p<0.001), were younger (t=5.86, df=267, p<0.001), and received lower doses of clozapine (t=-2.587, p=0.01) than those who did not develop neutropenia. CONCLUSION: We identified an association between the concurrent use of sodium valproate and an increased risk of clozapine associated neutropenia. These results, taken in combination with the results from previous case series, suggest that the risk of clozapine associated neutropenia could be reduced by avoiding concurrent valproate treatment.
BACKGROUND: The use of clozapine is limited due to the occurrence of neutropenia, and the rare but life threatening adverse event of agranulocytosis. There is little epidemiological research into clinical factors that may impact on this risk. We conducted a case control study examining the clinical risk factors for neutropeniapatients treated with clozapine. METHOD: A case-control study was conducted within a database of anonymised electronic clinical records. All patients who discontinued clozapine due to a neutropenic event were included as cases. Matched controls were selected from patients with a documented clozapine exposure at the time of the clozapineneutropenic event of the case patient, matched by duration of clozapine treatment. RESULTS: 136 cases and 136 controls were included. In multivariable analysis, the concurrent use of sodium valproate was associated with neutropenia (Odds Raito (OR) 2.28, 95%CI: 1.27-4.11, p=0.006). There was a dose-response effect, with greater associations for higher doses. Patients who discontinued clozapine due to neutropenia were more likely to be of black ethnicity (OR 2.99, p<0.001), were younger (t=5.86, df=267, p<0.001), and received lower doses of clozapine (t=-2.587, p=0.01) than those who did not develop neutropenia. CONCLUSION: We identified an association between the concurrent use of sodium valproate and an increased risk of clozapine associated neutropenia. These results, taken in combination with the results from previous case series, suggest that the risk of clozapine associated neutropenia could be reduced by avoiding concurrent valproate treatment.
Authors: Mina Boazak; Benjamin Kahn; Lindsay Cox; James Ragazino; David R Goldsmith; Robert O Cotes Journal: Clin Schizophr Relat Psychoses Date: 2018-06-26