Background/Objectives: Antipsychotic treatment response varies considerably between individuals, with one potential reason being genetic variation affecting the cytochrome P450 enzymes that metabolise them. Methods: With a diverse sample of 453 participants, we studied the influence of CYP1A2, CYP2D6, and CYP3A4 variation on three antipsychotic treatment outcomes: participant-reported adverse antipsychotic drug reactions, health-related quality of life, and the dose of antipsychotic medication prescribed. These measures were taken from the baseline assessment, before a pharmacogenetic intervention was delivered. Results: Over half of our sample (62.9%) were carriers of an allele associated with altered metabolism of antipsychotic medications on CYP2D6 or CYP3A4, the two genes with pharmacogenetic guidelines for antipsychotic medications. Ultrarapid CYP2D6 metabolisers reported significantly lower levels of adverse antipsychotic drug reactions than normal CYP2D6 metabolisers (mean difference: −11.1; 95% confidence interval [CI]: −18.9, −3.3; p = 0.00575). There was also suggestive evidence of lower quality of life scores in those carrying one (mean difference: −0.0863; 95% CI: −0.1806, 0.0081; p = 0.0731) or two copies (mean difference: −0.0803; 95% CI: −0.1734, 0.0129; p = 0.0914) of the CYP1A2*30-inducible allele. Conclusions: Our findings suggest that even when looking at a small number of cytochrome P450 genes, carrying an allele associated with altered antipsychotic medication metabolism is relatively common. We also found evidence that the CYP genotype can influence antipsychotic treatment outcomes, specifically adverse drug reactions and quality of life scores.

Background: Clozapine is the only licensed medication for treatment-resistant schizophrenia, although it is underused. Healthcare professionals (medical and non-medical professionals) play a crucial role in the management of clozapine. Consultant psychiatrists are accountable for the initiation of clozapine, whereas non-medical professionals are often responsible for the monitoring, the management of side effects and patient education. It appears that healthcare professionals‘ (HCPs) competence and confidence may have an effect on clozapine underutilisation. Aim: To synthesise the most pertinent literature examining the factors influencing HCPs competence and confidence in the management of clozapine and how these factors influence variation in prescribing practice. Methods: A review of the literature focusing on these elements was conducted. The Population, Context, Outcome (PCO) framework was adopted to support the literature search. The databases Medline, Psychinfo, Scopus, Cinahl, Pubmed, Embase, British Library, Ethos e-thesis, Google Scholar, Dart Europe e-thesis were consulted; the search was completed in January 2025. Screening, selection, data extraction and quality assessment were conducted independently by two researchers. Thematic analysis was used to investigate and compare the data emerging from the studies. Results: Thirty-four articles were included in the review. Six themes were identified: attitude toward and knowledge about clozapine, misconceptions (regarding side effects, monitoring and co-morbidities), guidelines, education, training and experience. HCPs self-reported as competent with guidelines (local and national), yet they expressed less confidence in their ability to adhere to them and were uncertain about managing side effects. Lack of education, training and insufficient exposure to clozapine management were significant factors impacting competence and confidence, resulting in clozapine underuse and variance in prescribing practice. The review highlighted a gap in the literature, as only a few studies involving non-medical professionals were found. Conclusions: A general lack of education and training related to clozapine use was identified amongst all professionals. The impact of educational programmes on improving competence and enhancing confidence was considered positive, however when integrated with clinical practice. The studies identified in this review were lacking in the involvement of non-medical professionals. Given their crucial role in managing side effects and educating patients and carers, it is evident that their inclusion in future research is imperative.

Background: many medications possess anticholinergic activity. Their use is associated with a number of serious adverse effects including cognitive effects. The cumulative anticholinergic effect of medications as assessed by tools such as the anticholinergic burden scale (AchB) can identify people particularly at risk of anticholinergic side-effects. Currently, >20 tools are available for clinicians to use, but there is no consensus on the most appropriate tool. Methods: a newly created online tool—International Anticholinergic Cognitive Burden Tool (IACT)—based on natural language processing and chemical structure analysis, was developed and made available for clinicians to test its functions. We carried out a survey (between 8th of February and 31st of March 2021) to assess the overall need for an assessment tool as well as the usability of the IACT. Results: a total of 110 responses were received from different countries and practitioners’ groups. The majority of the participants (86.11%) stated they would use a tool for AchB assessment if available and when they were asked to rate the IACT against other tools, amongst 34 responders, 20.59% rated it better and 8.82% rated it significantly better, 44.12% rated it neither better, nor worse, 14.71% rated it worse and 11.76% somewhat worse. Conclusion: there is a need for an anticholinergic burden calculator to assess the anticholinergicity of medications. Tools such as the IACT potentially could meet this demand due to its ability to assign scores to current and new medications appearing on the market based both on their chemical structure and reported adverse pharmacological effects.

Neutropenia and the more severe, potentially life-threatening agranulocytosis are recognized side effects of clozapine that require regular, mandatory, and life-long blood monitoring. However, most cases of haematological adverse effects occur in the first few months of treatment; therefore, there are now increasing calls for the termination of the mandatory monitoring after this initial period. In this report, we present a patient with treatment-resistant schizophrenia who was successfully treated with clozapine yet developed neutropenia after 9 years. This soon evolved into agranulocytosis requiring the use of granulocyte colony-stimulating factor and eventual clozapine cessation. Such late-onset cases of agranulocytosis are isolated and rare but should not impede the drive to relax mandatory clozapine haematological monitoring, but patients and carers must be aware of potential symptoms of agranulocytosis.

Background: Clozapine is the most effective treatment for individuals with treatment-resistant schizophrenia, but concerns about adverse effects continue to limit its use. In contrast to haematological monitoring, which is governed by established protocols, there is no standardised framework for detection of clozapine-associated myocarditis. Clozapine-induced myocarditis is rare but potentially fatal and typically occurs within the first 4 weeks of treatment. As early symptoms such as fever and tachycardia overlap with common side-effects of clozapine, diagnosis is often delayed, and clozapine may be unnecessarily discontinued. Evidence suggests that routine monitoring of troponin and C-reactive protein (CRP), alongside assessment of vital signs and electrocardiography (ECG), can support earlier detection and safer treatment. Aims: To evaluate cardiac monitoring practice in patients initiating clozapine treatment. Method: We undertook a retrospective review of all patients registered to start clozapine at Kent and Medway Mental Health National Health Service (NHS) Trust between January 2021 and March 2024. Data were collected on baseline ECG completion, weekly troponin and CRP testing during the first 4 weeks, and documented cardiac symptoms. Results: Of 219 patients, 180 had complete data. Baseline ECG was completed in 80% of cases. No routine troponin monitoring was identified, and CRP testing was infrequent. Tachycardia occurred in more than 40% of patients. Fifteen patients were referred to cardiology before initiation, as well as six in the first 4 weeks and five thereafter. Twelve patients (7%) discontinued clozapine early, mainly owing to tachycardia. Conclusions: The findings indicate an absence of systematic myocarditis monitoring. Incorporating weekly troponin and CRP testing into existing mandatory blood testing could improve safety, guide appropriate cardiology referrals and reduce unnecessary discontinuation.