The art of clozapine therapy and “clozaphobia”

Pandarakalam, James Paul

doi:10.1136/bmj.l484

Cited by 12 publications

(12 citation statements)

References 5 publications

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“…Conversely, current findings emphasized a range of severe and fatal health consequences associated with clozapine high-dosage intake, and patients taking clozapine should be educated thoroughly about the risks associated with polydrug intake. In being a prescribed drug of highly significant clinical value [85], increased awareness is essential towards prevention, diagnosis, and treatment of cases of clozapine abuse/recreational use in patients diagnosed with schizophrenia [86].…”

Section: Discussionmentioning

confidence: 99%

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

et al. 2020

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Background: Clozapine is of high clinical relevance for the management of both treatment-resistant schizophrenia and psychotic disturbances with concurrent drug misuse. Although the molecule presents with a range of well-known side-effects, its discontinuation/withdrawal syndrome has been only anecdotally described. Aims: the 2005–2018 European Medicines Agency (EMA) dataset of Adverse Drug Reactions (ADRs) was analyzed to identify and describe possible clozapine withdrawal- and misuse-/abuse-/dependence-related issues. Method: A descriptive analysis of clozapine-related ADRs was performed when available, data on ADRs’ outcome, dosage, and possible concomitant drug(s) were considered. Results: Out of 11,847 clozapine-related ADRs, some 599 (5.05%) were related to misuse/abuse/dependence/withdrawal issues, including 258 withdrawal-related (43.1%); 241 abuse-related (40.2%); and 80 intentional product misuse-related (13.3%) ADRs. A small number of overdose- and suicide-related ADRs were reported as well. Clozapine was typically (69.2%) identified alone, and most (84.7%) fatalities/high-dosage intake instances were reported in association with a history of substance abuse. Conclusions: Previous suggestions about the possibility of a clozapine discontinuation/withdrawal occurrence are here supported, but further studies are needed. However, the misuse/abuse cases here identified might be difficult to interpret, given the lack of studies highlighting the possible recreational use of clozapine. The high-dosage intake, fatal outcomes and clozapine/polydrug abuse issues reported here may, however, be a reason for concern.

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Section: Discussionmentioning

confidence: 99%

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

et al. 2020

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“…At a patient level, the underutilisation of clozapine in treatment-resistant psychosis (TRP) is associated with decreased interpersonal and occupational functioning, decreased quality of life and increased caregiver burden and hospitalisation 5 , 6 . While clozapine underuse is likely to be multifactorial, one purported factor is clinician perception 7 , 8 . Specifically, studies have suggested that clinicians may overemphasis the negative aspects of clozapine treatment, particularly in comparison to patient views 9 .…”

Section: Introductionmentioning

confidence: 99%

What are the barriers and facilitators of clozapine use in early psychosis? A survey of UK early intervention clinicians

Oloyede¹,

Blackman²,

Mantell³

et al. 2023

Schizophr

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Clozapine is the most effective medication for treatment-resistant psychosis, but evidence points to substantial underuse, especially within early intervention psychosis (EIP) services. We explored clinicians’ views on perceived barriers and facilitators to offering patients clozapine within EIP services. A cross-sectional survey was distributed electronically to clinicians practising in EIP services across England. A mixed methods approach was used to assess barriers to clozapine, and attitudes and opinions concerning clozapine underutilisation. Based on the barriers identified in the literature, clinicians were asked to rate each one (scale:1-7) based on importance, with a higher score indicating higher importance. Clinicians were also asked open-ended questions on barriers to clozapine and how access can be improved in EIP services. Quantitative data were analysed using descriptive and inferential statistics, and qualitative responses were analysed thematically. One hundred and nineteen EIP clinicians from 35 services in England completed the survey. In total, 37% (n = 45) of clinicians perceived that clozapine was under-prescribed in their EIP service. The most important barrier to utilising clozapine were patient concerns with side effects, followed by monitoring requirements and clinician concerns with side effects. Thematic analysis identified 17 perceived barriers, which were grouped into three major themes: administrative (5 subthemes), clinician-related (6 subthemes), and patient-related (6 subthemes). Perceived facilitators to improving clozapine use were greater training, improved resources, and optimised monitoring. The main barriers to clozapine in EIP services, as identified by clinicians, are patient concerns regarding side effects and monitoring requirements. Identified facilitators for improved clozapine use include clinician training, improved resources, guidelines, and point-of-care testing.

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“…In particular, clinician concerns about adverse drug reactions and the need for regular monitoring with clozapine may contribute towards a reluctance to prescribe clozapine, so-called ‘clozaphobia’. 5 , 6 Other suggested contributors to clozapine’s underuse include a lack of prescribing experience among clinicians. 7 …”

Section: Introductionmentioning

confidence: 99%

“…In particular, clinician concerns about adverse drug reactions and the need for regular monitoring with clozapine may contribute towards a reluctance TherapeuTic advances in psychopharmacology to prescribe clozapine, so-called 'clozaphobia'. 5,6 Other suggested contributors to clozapine's underuse include a lack of prescribing experience among clinicians. 7 In the United Kingdom, Early Intervention in Psychosis (EIP) services provide a comprehensive range of psychological, social and pharmacological interventions to patients experiencing a first episode of psychosis.…”

Section: Introductionmentioning

confidence: 99%

Clozapine for treatment resistance in early psychosis: a survey of UK clinicians’ training, knowledge and confidence

Oloyede

Mantell

Williams

et al. 2022

Therapeutic Advances in Psychopharmacology

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Background: Clozapine is the only medication licenced for patients with psychosis that is resistant to conventional antipsychotic treatment. However, despite its effectiveness, it remains widely underutilised. One contributory factor for this may be clinicians’ lack of confidence around the management of clozapine. Objective: We conducted a survey of clinicians working in Early Intervention in Psychosis (EIP) services to determine their training needs for clozapine management in EIP services. Methods: An electronic survey was made available to all clinicians working in EIP services in England. The survey assessed confidence and training needs regarding managing clozapine in patients with treatment-resistant psychosis. Quantitative data were analysed using total mean scores and the Mann–Whitney U test. Results: In all, 192 (27%) of approximately 700 clinicians from 35 EIP services completed the survey. Approximately half (54%) had not received training on treatment with clozapine. Experience of training was higher in prescribers than non-prescribers, and among medical than non-medical clinicians. Previous training was associated with significantly higher confidence in offering clozapine and managing treatment-resistant psychosis ( p < 0.001). Confidence levels with managing treatment-resistant psychosis and clozapine were relatively high (mean = 4 out of 5, SD = 1). Respondents were most confident about monitoring mental health response to treatment (mean = 5, SD = 1). Participants were least confident about how to discontinue clozapine treatment safely (mean = 3, SD = 1). Conclusion: Most clinicians working in EIP have not received training on the use of clozapine. This may account, in part, for the underutilisation of clozapine in EIP services. The provision of training in the identification of treatment-resistant psychosis and the use of clozapine will likely improve the detection and management of treatment resistance in the early phase of psychosis.

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The art of clozapine therapy and “clozaphobia”

Cited by 12 publications

References 5 publications

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

What are the barriers and facilitators of clozapine use in early psychosis? A survey of UK early intervention clinicians

Clozapine for treatment resistance in early psychosis: a survey of UK clinicians’ training, knowledge and confidence

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