Maria Concepcion Turrion1, Jesus Perez2, Miguel Bernardo3, Emilio Fernandez-Egea4. 1. Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, Reino Unido. 2. Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, Reino Unido; Department of Psychiatry, University of Cambridge, Cambridge, Reino Unido; Norwich Medical School, University of East Anglia (UEA), Norwich, Reino Unido. 3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, España; Unidad Esquizofrenia Barcelona Clinic, Neuroscience Institute, Hospital Clinic of Barcelona, Barcelona, España; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España; University of Barcelona, España. 4. Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, Reino Unido; Department of Psychiatry, University of Cambridge, Cambridge, Reino Unido; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, Reino Unido. Electronic address: ef280@cam.ac.uk.
Abstract
INTRODUCTION: Clozapine plasma levels are useful to monitor drug compliance, and also to assess and to prevent some side effects. Recently, routine monitoring to all clozapine-treated patients has been proposed to prevent relapses. However, high intra-individual variability in plasma levels has been reported too, although these studies have some limitations. METHODS: We analysed differences between 2clozapine plasma levels separated by at least one year in a subgroup of 28 outpatients (82% male, mean age 47.9 years-old) with diagnosis of non-affective psychosis in clinical remission whose clozapine doses and smoking habits remained unchanged. RESULTS: We found a non-significant increase in clozapine plasma levels [.30mg/L (SD=.14) vs. .32 (SD=.17); t=-.858, p=.40] and a significant decrease in norclozapine plasma levels [.27 (SD=.11) vs. .22 (SD=.10); t=3.27; p=.003]. Absolute coefficient of variation (CV) between first and second assessment were calculated. Forty-six and fifty-seven percent of cases had CV 20% in clozapine and norclozapine, respectively. CV of 50% was seen in 20.7% and 13.8% of clozapine and norclozapine test respectively. We discussed potential causes of such high CV. CONCLUSIONS: Our study suggest high intra-individual variation even in a subgroup of very stable patients, which suggest that routine monitoring of these levels may be indicated in order to detect significant plasma variations. We think that clinicians should act with caution in case of a sudden decrease in plasma level. In the absence of obvious symptom severity variation, sources of intra-individual fluctuations might be considered first, before assuming poor compliance.
INTRODUCTION:Clozapine plasma levels are useful to monitor drug compliance, and also to assess and to prevent some side effects. Recently, routine monitoring to all clozapine-treated patients has been proposed to prevent relapses. However, high intra-individual variability in plasma levels has been reported too, although these studies have some limitations. METHODS: We analysed differences between 2clozapine plasma levels separated by at least one year in a subgroup of 28 outpatients (82% male, mean age 47.9 years-old) with diagnosis of non-affective psychosis in clinical remission whose clozapine doses and smoking habits remained unchanged. RESULTS: We found a non-significant increase in clozapine plasma levels [.30mg/L (SD=.14) vs. .32 (SD=.17); t=-.858, p=.40] and a significant decrease in norclozapine plasma levels [.27 (SD=.11) vs. .22 (SD=.10); t=3.27; p=.003]. Absolute coefficient of variation (CV) between first and second assessment were calculated. Forty-six and fifty-seven percent of cases had CV 20% in clozapine and norclozapine, respectively. CV of 50% was seen in 20.7% and 13.8% of clozapine and norclozapine test respectively. We discussed potential causes of such high CV. CONCLUSIONS: Our study suggest high intra-individual variation even in a subgroup of very stable patients, which suggest that routine monitoring of these levels may be indicated in order to detect significant plasma variations. We think that clinicians should act with caution in case of a sudden decrease in plasma level. In the absence of obvious symptom severity variation, sources of intra-individual fluctuations might be considered first, before assuming poor compliance.
Authors: Selene R T Veerman; Timo Moscou; Jan P A M Bogers; Dan Cohen; Peter F J Schulte Journal: Acta Psychiatr Scand Date: 2022-04-01 Impact factor: 7.734