The side effect profile of Clozapine in real world data of three large mental health hospitals

Abstract

Objective Mining the data contained within Electronic Health Records (EHRs) can potentially generate a greater understanding of medication effects in the real world, complementing what we know from Randomised control trials (RCTs). We Propose a text mining approach to detect adverse events and medication episodes from the clinical text to enhance our understanding of adverse effects related to Clozapine, the most effective antipsychotic drug for the management of treatment-resistant schizophrenia, but underutilised due to concerns over its side effects. Material and methods We used data from de-identified EHRs of three mental health trusts in the UK (>50 million documents, over 500,000 patients, 2835 of which were prescribed Clozapine). We explored the prevalence of 33 adverse effects by age, gender, ethnicity, smoking status and admission type three months before and after the patients started Clozapine treatment. Where possible, we compared the prevalence of adverse effects with those reported in the Side Effects Resource (SIDER). Results Sedation, fatigue, agitation, dizziness, hypersalivation, weight gain, tachycardia, headache, constipation and confusion were amongst the highest recorded Clozapine adverse effect in the three months following the start of treatment. Higher percentages of all adverse effects were found in the first month of Clozapine therapy. Using a significance level of (p< 0.05) our chi-square tests show a significant association between most of the ADRs and smoking status and hospital admission, and some in gender, ethnicity and age groups in all trusts hospitals. Later we combined the data from the three trusts hospitals to estimate the average effect of ADRs in each monthly interval. In gender and ethnicity, the results show significant association in 7 out of 33 ADRs, smoking status shows significant association in 21 out of 33 ADRs and hospital admission shows the significant association in 30 out of 33 ADRs. Conclusion A better understanding of how drugs work in the real world can complement clinical trials.

Clozapine resistant schizophrenia: Newer avenues of management

“…Women are more likely to develop hyperglycaemia and diabetes and increases in weight and body mass index[ 122 , 126 ]. There is very little evidence of gender differences in other side effects, though certain studies have found haematological abnormalities and constipation to be commoner among women[ 122 , 125 , 128 , 129 ].…”

“…Therefore, Asian patients need lower doses at the start of treatment and slower upward titration to reach their optimum dose. Despite these pharmacokinetic dissimilarities, ethnic differences seem to have minimal impact on the prevalence of adverse effects of clozapine[ 129 ]. Nevertheless, non-White ethnicity is a risk factor for metabolic syndrome, and certain studies have found a higher prevalence of hypertension and weight gain in Asians[ 127 , 136 ].…”

Transient drop in the neutrophil count during COVID-19 regardless of clozapine treatment in patients with mental illness

“…In this sense, the use of clozapine, an atypical antipsychotic medication indicated for treatment-refractory schizophrenia 9 has been associated to an increased susceptibility to COVID-19 infection compared with other antipsychotic medications. 10 Moreover, prescribing clozapine requires close monitoring for serious adverse events, including agranulocytosis, myocarditis, aspiration pneumonia, and clozapine toxicity, as seizures, ileus and delirium, 11 , 12 which could be higher in the setting of COVID-19, as clozapine plasma concentrations increase during acute systemic infection because of the CYP1A2 enzymes’ inhibition by cytokines, 13 and the reduction or ceasing tobacco smoking in patients during acute illness. 14 …”

Factors impeding switching from clozapine to paliperidone among patients with chronic schizophrenia—A retrospective cohort study.

“…Moreover, clozapine has more favorable efficacy on negative and depressive symptoms than paliperidone (Huhn et al, 2019). However, clozapine has several undesirable side effects, including over sedation, constipation, dizziness, hypersalivation, weight gain, tachycardia, headache, and constipation (Iqbal et al, 2020; Siskind et al, 2016). Metabolic syndrome has also been reported to be an undesirable adverse effect in patients taking clozapine (Wirshing et al, 1998), as it can lead to multiple systemic diseases.…”