Moving forward with clozapine

Schulte, Peter F.J.; Bogers, Jan P.A.M.; Veerman, Selene R. T.; Cohen, Dan

doi:10.1111/acps.13224

Cited by 13 publications

(12 citation statements)

References 17 publications

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“…Our findings complement a previous study by Nielsen et al ., 2016 that investigated broader aspects of international guidelines of clozapine use (Nielsen et al ., 2016), and are of particular interest in the context of growing concerns about the underutilisation of clozapine in TRP. Several authors have called for the easing of restrictive guidelines, such as those mandating lifelong, frequent haematological monitoring or prohibiting rechallenge after haematological values fall below a particular threshold (Schulte et al ., 2020; Siskind and Nielsen, 2020; Oloyede et al ., 2021a).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, several recent meta-analyses have shown that the risk of clozapine-induced severe neutropenia is highest in the first 6 months (Myles et al ., 2018; Myles et al ., 2019). Cumulatively, this casts doubts on the clinical utility of stringent haematological monitoring beyond the first six months of treatment, especially when considering the impact of premature discontinuation of clozapine on morbidity (Schulte, 2006; Shrivastava and Shah, 2009; Rettenbacher et al ., 2010; Myles et al ., 2018, 2019; Luykx et al ., 2020; Schulte et al ., 2020; Siskind and Nielsen, 2020; Johannsen et al ., 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Haematological Monitoring is an intrinsic component of treatment with clozapine (Farooq et al ., 2019; Schulte et al ., 2020). Our review shows that most countries require that this continues throughout the duration of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Over recent decades, the number of guidelines for schizophrenia, including haematological monitoring in the context of clozapine treatment have increased in both high and middle-income countries (Warnez and Alessi-Severini, 2014; Nielsen et al ., 2016). Several recent investigations have shown that excessively rigid guidelines, that prioritise risk minimisation without balancing this against the superior efficacy of clozapine, can lead to clozapine being withheld from patients for whom it represents their only hope of recovery (Schulte, 2006; Myles et al ., 2018, 2019; Whiskey et al ., 2019; Schulte et al ., 2020; Oloyede et al ., 2021a, 2021b). Preliminary investigations and existing literature suggest there are marked variations in key recommendations around monitoring between countries (Nielsen et al ., 2016; Bachmann et al ., 2017; Whiskey et al ., 2021).…”

Section: Introductionmentioning

confidence: 99%

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Clozapine haematological monitoring for neutropenia: a global perspective

Oloyede

Blackman

Whiskey

et al. 2022

Epidemiol Psychiatr Sci

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clozapine haematological monitoring for neutropenia: a global perspective

Oloyede

Blackman

Whiskey

et al. 2022

Epidemiol Psychiatr Sci

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“…There is some evidence that educational interventions improve the rates and quality of clozapine prescriptions. These educational interventions include Dutch [6], the United States [7], Australia [8], and New Zealand [9] examples. The content of these educational interventions varies but essentially covers following aspects: increased training in clozapine in identifying suitable patients for clozapine, education in side effects management, developing and implementing standardized protocols for medical review, supporting documentation and adverse event management, shared decision-making, and training in use of point care devices.…”

mentioning

confidence: 99%

Mandatory certification for clozapine prescribing

Cohen¹,

Farooq

2020

Eur. Psychiatr.

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The Clozapine Prescription Rates and Current Clinical Practice Clozapine is the only registered treatment for therapy-resistant schizophrenia (meaning, after treatment with two other antipsychotics failed or were not tolerated), psychosis in Parkinson's disease, and, in the United States, for suicidality. Off-label, clozapine is prescribed for therapyresistant disorders, especially therapy-resistant bipolar, borderline personality, violent behavior, or self-harm in patients with psychosis, aggressive behavior, or addiction to cannabis in psychotic disorder and in the animal model. Despite the good evidence of efficacy [1] and now robust evidence that clozapine use may be associated with lowered mortality compared to other antipsychotics [2], the use of clozapine remains suboptimal in most countries, both within and outside Europe [3]. Low prescription rates not only result in poor treatment for schizophrenia, an unintended consequence is that trainees and consultants in psychiatry have less experience and, therefore, lack confidence in initiating and maintaining the clozapine therapy. In a major survey of UK practice, it was found that almost one third of senior consultants have not prescribed the clozapine, for more than a year. It appears that a vicious cycle sets in; because clozapine is less prescribed, doctors have less exposure and confidence in prescribing it which in turn results in even lesser exposure to managing the drug and its side effects. Not surprisingly, this promotes the aura for clozapine as a dangerous drug, which results in prescribers' fear.

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Part II: Interactive case—Clinical pearls of clozapine

Leung¹

2023

J Am Coll Clin Pharm

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Moving forward with clozapine

Cited by 13 publications

References 17 publications

Clozapine haematological monitoring for neutropenia: a global perspective

Clozapine haematological monitoring for neutropenia: a global perspective

Mandatory certification for clozapine prescribing

Part II: Interactive case—Clinical pearls of clozapine

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