TY - JOUR
T1 - Clozapine haematological monitoring for neutropenia
T2 - a global perspective
AU - Oloyede, Ebenezer
AU - Blackman, Graham
AU - Whiskey, Eromona
AU - Bachmann, Christian
AU - Dzahini, Olubanke
AU - Shergill, Sukhi
AU - Taylor, David
AU - McGuire, Philip
AU - MacCabe, James
N1 - Publisher Copyright:
© The Author(s), 2022. Published by Cambridge University Press.
PY - 2022/11/25
Y1 - 2022/11/25
N2 - Aims. Clozapine is licensed for treatment-resistant psychosis and remains underutilised. This may berelated to the stringent haematological monitoring requirements that are mandatory in most countries. We aimed to compare guidelines internationally and develop a novel Stringency Index. We hypothesised that the most stringent countries would have increased healthcare costs and reduced prescription rates. Method. We conducted a literature review and survey of guidelines internationally. Guideline identification involved a literature review and consultation with clinical academics. We focused on the haematological monitoring parameters, frequency and thresholds for discontinuation and rechallenge after suspected clozapine-induced neutropenia. In addition, indicators reflecting monitoring guideline stringency were scored and visualised using a choropleth map. We developed a Stringency Index with an international panel of clozapine experts, through a modified-Delphi-survey. The Stringency Index was compared to health expenditure per-capita and clozapine prescription per 100 000 persons. Results. One hundred twocountries were included, from Europe (n = 35), Asia (n = 24), Africa (n = 20), South America (n = 11), North America (n = 7) and Oceania and Australia (n = 5). Guidelines differed in frequency of haematological monitoring and discontinuation thresholds. Overall, 5% of included countries had explicit guidelines for clozapine-rechallenge and 40% explicitly prohibited clozapine-rechallenge. Furthermore, 7% of included countries had modified discontinuation thresholds for benign ethnic neutropenia. None of the guidelines specified how long haematological monitoring should continue. The most stringent guidelines were in Europe, and the least stringent were in Africa and South America. There was a positive association (r = 0.43, p < 0.001) between a country’s Stringency Index and healthcare expenditure per capita. Conclusions. Recommendations on how haematological function should be monitored in patients treated with clozapine vary considerably between countries. It would be useful to standardise guidelines on haematological monitoring worldwide.
AB - Aims. Clozapine is licensed for treatment-resistant psychosis and remains underutilised. This may berelated to the stringent haematological monitoring requirements that are mandatory in most countries. We aimed to compare guidelines internationally and develop a novel Stringency Index. We hypothesised that the most stringent countries would have increased healthcare costs and reduced prescription rates. Method. We conducted a literature review and survey of guidelines internationally. Guideline identification involved a literature review and consultation with clinical academics. We focused on the haematological monitoring parameters, frequency and thresholds for discontinuation and rechallenge after suspected clozapine-induced neutropenia. In addition, indicators reflecting monitoring guideline stringency were scored and visualised using a choropleth map. We developed a Stringency Index with an international panel of clozapine experts, through a modified-Delphi-survey. The Stringency Index was compared to health expenditure per-capita and clozapine prescription per 100 000 persons. Results. One hundred twocountries were included, from Europe (n = 35), Asia (n = 24), Africa (n = 20), South America (n = 11), North America (n = 7) and Oceania and Australia (n = 5). Guidelines differed in frequency of haematological monitoring and discontinuation thresholds. Overall, 5% of included countries had explicit guidelines for clozapine-rechallenge and 40% explicitly prohibited clozapine-rechallenge. Furthermore, 7% of included countries had modified discontinuation thresholds for benign ethnic neutropenia. None of the guidelines specified how long haematological monitoring should continue. The most stringent guidelines were in Europe, and the least stringent were in Africa and South America. There was a positive association (r = 0.43, p < 0.001) between a country’s Stringency Index and healthcare expenditure per capita. Conclusions. Recommendations on how haematological function should be monitored in patients treated with clozapine vary considerably between countries. It would be useful to standardise guidelines on haematological monitoring worldwide.
KW - Adverse drug reaction
KW - national guidelines
KW - safety
KW - stringency index
KW - tolerability
KW - treatment discontinuation
KW - treatment-resistant schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85142658289&partnerID=8YFLogxK
U2 - 10.1017/S204579602200066X
DO - 10.1017/S204579602200066X
M3 - Article
C2 - 36426600
AN - SCOPUS:85142658289
SN - 2045-7960
VL - 31
JO - Epidemiology and Psychiatric Sciences
JF - Epidemiology and Psychiatric Sciences
M1 - e83
ER -