Need to bleed? Clozapine haematological monitoring approaches a time for change

Whiskey, Eromona; Dzahini, Olubanke; Ramsay, Rosalind; O'Flynn, David; Mijović, Aleksandar; Gaughran, Fiona; MacCabe, James H.; Shergill, Sukhi; Taylor, David

doi:10.1097/yic.0000000000000258

Cited by 17 publications

(15 citation statements)

References 22 publications

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“…There are many reported barriers to clozapine prescribing, including concerns over need for blood testing and potential for side-effects but also clinician and patient attitudes to clozapine [89][90][91]. Recent authors have highlighted the need to review stringent blood monitoring requirements for clozapine, which can lead to unnecessary treatment discontinuation [92]. This review helps shore up the evidence base for the use of clozapine in schizophrenia, which has not responded to first-line treatment, and provides some qualified support for the hypothesis that using clozapine earlier in the course of illness is more effective, which it is hoped should help surmount some of these barriers.…”

Section: Discussionmentioning

confidence: 99%

Effect of age on the relative efficacy of clozapine in schizophrenia

Jones

MacCabe

Price

et al. 2020

Acta Psychiatr Scand

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Objective: Early treatment of schizophrenia improves outcomes. Clozapine appears to have unique benefit when other antipsychotic medication has failed. This systematic review and meta-analysis aims to assess clozapine's superiority over alternative antipsychotic medication and examine whether earlier use is associated with additional benefit. Method: Systematic retrieval of blinded, randomized controlled trials comparing clozapine with alternative antipsychotics in adults with schizophrenia. The effect of mean age on relative clozapine response was examined using random effects meta-regression, and multiple linear regression on available patient data. Results: A total of 276 studies were retrieved. Thirty-four studies were included in the meta-analysis. Clozapine was significantly more effective than alternative antipsychotics in reducing psychotic symptoms and increasing response. However, meta-regression failed to show a more significant effect in younger patients (age on effect size (total psychotic symptoms) 0.00, P = 0.79 CI À0.03 to 0.03). Individual patient data were available for two studies, the larger of which showed a significant interaction between younger age and superiority of clozapine. Conclusion: The results support clozapine's superiority over other antipsychotics. A convincing effect of age on this effect was not demonstrated, although this was suggested in one study. In view of the age of many of the included studies, and changes in reporting practice over time, new clozapine RCTs, which include age of illness onset as well as age at trial time, would be welcome in order to provide metaanalysable data for future use.

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Section: Discussionmentioning

confidence: 99%

Effect of age on the relative efficacy of clozapine in schizophrenia

Jones

MacCabe

Price

et al. 2020

Acta Psychiatr Scand

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“…In particular a simple revision of the neutrophil thresholds on an off-license basis. Better still would be wholesale change to align UK and US practice (78).…”

Section: Discussionmentioning

confidence: 99%

Clozapine Re-Challenge and Initiation Despite Neutropenia and Outcomes from 14 Patients

Silva

Higgins

Hammer

et al. 2019

Preprint

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Objective: Clozapine remains the most effective intervention for treatment resistant schizophrenia. But its use is limited because of the risk of neutropenia and agranulocytosis. In the absence of effective alternatives its use after blood dyscrasias is possible. Methods: A case series of 14 male patients with treatment resistant schizophrenia treated with clozapine despite previous episodes of neutropenia between 2006 and 2015 is presented. Data were collected during 2015 and 2019. Using routinely collected clinical data we describe the patient characteristics, causes of neutropenia, the strategies used and outcomes. Results: Previous neutropaenia was due to varying aetiologies: benign ethnic neutropaenia; clozapine induced; other medication; autoimmune. A range of risk mitigation strategies were used to prevent neutropaenia on clozapine rechallenge: G-CSF; lithium; watch and wait. There were no serious adverse events associated with clozapine or risk mitigation treatments. At follow up during 2019, half of the original 14 patients had improved sufficiently to transfer to conditions of lesser security. Conclusion: With careful planning and monitoring, taking into account what is known about neutrophil biology, clozapine can be successfully reinitiated following CIN or in the face of preexisting neutropenia resulting in significant benefits for patients.

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“…A lower threshold is available for patients with a heamatologicaly confirmed diagnosis of Benign Ethnic Neutropenia (BEN). The UK requirements have not yet aligned to use the lower neutrophil thresholds now used in the United States [12]. Afternoon blood sampling may optimise clozapine blood testing, ideally after exercise; this alone has been demonstrated to be sufficient to improve outcomes [13].…”

Section: Clozapine and Neutropeniamentioning

confidence: 99%

“…Alternatively, following consultation with the clozapine monitoring service and a haematologist alongside an assessment of the risk of clozapine withdrawal and the degree of patient compliance, arrangements can be made for accepting lower neutrophil count thresholds before clozapine must be stopped: 1.0 × 10 9 /L or lower. In the United States these thresholds have recently been lowered [12]. In an oncology setting, action is not taken for absolute neutrophil counts below 0.5 × 10 9 /L unless there is evidence of infection [48]; however, in the mental health setting, risks are associated with this approach since patient cooperation may be minimal and the difficulties of managing an uncooperative physically sick patient extreme.…”

Section: Clozapine Alonementioning

confidence: 99%

Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide

et al. 2020

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Clozapine remains the only drug treatment likely to benefit patients with treatment resistant schizophrenia. Its use is complicated by an increased risk of neutropenia and so there are stringent monitoring requirements and restrictions in those with previous neutropenia from any cause or from clozapine in particular. Despite these difficulties clozapine may yet be used following neutropenia, albeit with caution. Having had involvement with 14 cases of clozapine use in these circumstances we set out our approach to the assessment of risks and benefits, risk mitigation and monitoring with a practical guide.

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Need to bleed? Clozapine haematological monitoring approaches a time for change

Cited by 17 publications

References 22 publications

Effect of age on the relative efficacy of clozapine in schizophrenia

Effect of age on the relative efficacy of clozapine in schizophrenia

Clozapine Re-Challenge and Initiation Despite Neutropenia and Outcomes from 14 Patients

Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide

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