Search

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., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: D.T. is the Editor-in-Chief of Therapeutic Advances in Psychopharmacology; therefore, the peer-review process was managed by alternative members of the Board and the submitting Editor was not involved in the decision-making process., (© The Author(s), 2022.)

Background: Clozapine is the only medication licenced for treating patients with treatment-refractory schizophrenia. However, there are no evidence-based guidelines as to the optimal plasma level of clozapine to aim for, and their association with clinical and functional outcome., Objective: We assessed the relationship between clinical and functional outcome measures and blood concentrations of clozapine among patients with treatment-refractory psychosis., Methods: Data were reviewed in 82 patients with treatment-refractory psychosis admitted to a specialised tertiary-level service and treated with clozapine. Analysis focussed on the relationship between clozapine and norclozapine plasma concentrations and the patient's clinical symptoms and functional status., Results: Clinical symptom improvement was positively correlated with norclozapine plasma concentrations and inversely correlated with clozapine to norclozapine plasma concentrations ratio. Clozapine concentrations showed a bimodal association with clinical improvement (peaks around 350 and 660 ng/ml). Clinical symptom improvement correlated with functional outcomes, although there was no significant correlation between the latter and clozapine or norclozapine plasma concentrations., Conclusion: Clozapine treatment was associated with optimal clinical improvement at two different peak plasma concentrations around 350 and 650 ng/ml. Clinical improvement was associated with functional outcome; however, functionality was not directly associated with clozapine concentrations. A subset of patients may require higher clozapine plasma concentrations to achieve clinical improvement., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

Background: In addition to mandatory haematological monitoring, treatment guidelines recommend routine monitoring of adverse effects and physical health in patients prescribed clozapine., Methods: NHS trusts/healthcare organisations participated in a clinical audit in the context of a UK quality improvement programme addressing clozapine-prescribing practice., Results: Data relating to 6948 adult patients prescribed clozapine were submitted by 63 NHS trusts/healthcare organisations. Of 481 patients treated with clozapine for up to 18 weeks, there was documented pretreatment screening of blood pressure, heart rate and ECG in at least 90%, and body weight, plasma lipids, plasma glucose/glycated haemoglobin (HbA1c) and physical examination in approximately 80%. During the first 2 weeks of clozapine treatment there was documented daily measurement of both heart rate and blood pressure in 82% and body temperature in 77%. In a subsample of 411 patients, of the 72% who had weekly side-effect assessments documented in the first month of treatment, a structured assessment tool had been used in 29%. Treatment monitoring up to 18 weeks included an ECG in 90%, C-reactive protein (CRP) or creatine kinase in 42%, and troponin or B-type natriuretic peptide (BNP) in 29%. In the 5908 patients prescribed clozapine for at least 1 year, blood pressure and body weight/body mass index were documented in at least 80%, plasma lipids in 78% and plasma glucose in 73%, with an ECG in 55%. Two-thirds were prescribed medication to manage side effects of clozapine and one third of those with a diagnosis of schizophrenia were prescribed a second antipsychotic medication., Conclusion: The findings suggest that for most patients treated with clozapine in UK mental health services, physical health screening and side-effect monitoring follow recommended practice, but there was limited use of structured side-effect assessment tools. Monitoring for clozapine-induced myocarditis during the early risk period using markers of inflammation such as CRP, and cardiac damage such as troponin and BNP, was less consistent. This may partly reflect the variation in guideline recommendations for monitoring for myocarditis and partly the selected use of such tests when prompted by cardiac symptoms. The relatively common coprescription of medications for the majority of people on longer-term clozapine treatment may well further increase side-effect burden and physical health risks, reinforcing the need for continuing systematic monitoring., Competing Interests: Conflict of interest statement: TREB has been a member of scientific advisory boards for Lundbeck, Newron and Gedeon Richter/Recordati and received an honorarium for a lecture from Janssen. JMK has received honoraria for lectures and/or consulting from Alkermes, Allergan, Intra-Cellular Therapies, Janssen, LB Pharma, Lundbeck, Merck, Neurocrine Biosciences, Newron, Otsuka, Reviva, Roche, Sunovion, Sumitomo Dainippon and Teva. He is a shareholder in LB Pharma and the Vanguard Research Group., (© The Author(s), 2020.)

Cigarette smoking is strongly associated with psychotic disorders such as schizophrenia. For several decades it was assumed that the relationship could be explained by reverse causation; that smoking was secondary to the illness itself, either through self-medication or a process of institutionalization, or was entirely explained by confounding by cannabis use or social factors. However, studies have exposed that such hypotheses cannot fully explain the association, and more recently a bidirectional relationship has been proposed wherein cigarette smoking may be causally related to risk of psychosis, possibly via a shared genetic liability to smoking and psychosis. We review the evidence for these candidate explanations, using findings from the latest epidemiological, neuroimaging, genetic and preclinical work., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Background: Tobacco smoke is known to affect plasma levels of some drugs, including the antipsychotic clozapine. The effects of suddenly stopping smoking on patients who take clozapine can be severe, as plasma concentrations are expected to rapidly rise, potentially leading to toxicity. A ban on smoking at South London and the Maudsley NHS Foundation Trust (SLaM) was implemented in 2014, and this was expected to affect the plasma concentrations of clozapine for inpatients at the time. This study aimed to determine whether plasma concentrations of clozapine were affected, and additionally, in line with observations from other authors, whether levels of reported violence would also be affected., Methods: The smoking habits of all patients at SLaM who smoked and were prescribed clozapine were recorded both before and after the ban. The Glasgow Antipsychotic Side Effect Scale for Clozapine (GASS-C) scale was used to evaluate side-effect burden. Clozapine doses and plasma concentrations were also collected., Results: In total, 31 patients were included in this study. The mean clozapine dose before the ban was 502 mg/day, and this did not change significantly after the ban. Similarly, there were no significant changes in clozapine or norclozapine plasma concentrations, or in GASS-C scores. There was no change in the amount of tobacco patients reported smoking before or after the ban. A modest but statistically significant reduction in violent incidences was observed., Conclusions: Our data suggest that a ban on smoking for patients taking clozapine on open wards at inpatient hospital sites had little impact on clozapine plasma concentrations, because patients continued to smoke tobacco if allowed to leave. Smoking bans may result in a reduction in violent incidences., Competing Interests: Conflict of interest statement: Ms Gee has received consultancy fees from Sunovion, and lecturing honoraria from Sunovion, Otsuka and Janssen. Professor Taylor has received research funding from Janssen, Lundbeck and Servier; consultancy fees from Sunovion, and lecturing honoraria from Janssen, Otsuka and Servier.

Objectives: Clozapine is the most efficacious treatment for treatment-resistant schizophrenia; however its use can be limited by intolerability. Sinus tachycardia is a common adverse event associated with clozapine use, which may lead to the premature discontinuation of clozapine. Traditionally, β blockers are used to treat clozapine-associated tachycardia, though problems with intolerability and ineffectiveness can limit their utility., Methods: In this article, we present two cases of patients with treatment-resistant schizophrenia who developed symptomatic tachycardia associated with clozapine therapy., Results: We demonstrate that the novel heart rate controlling agent ivabradine can be effectively and safely used to control the heart rate and to allow for continued treatment with clozapine., Conclusion: This is the first report in the literature demonstrating that ivabradine appears to be a well tolerated agent, which should be considered as a symptomatic treatment of clozapine-induced tachycardia if the use of a β blocker fails due to a lack of response or intolerability.