3 results
Modelling Clozapine Levels to Identify Safe Titration Targets and a Method for Precise Dose Adjustment
- Zeryab Meyer, Gemma Simpson, Richard J Drake
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- Journal:
- BJPsych Open / Volume 10 / Issue S1 / June 2024
- Published online by Cambridge University Press:
- 01 August 2024, p. S64
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Aims
A precision medicine approach to clozapine dosing aims to personalise it in two ways: i) during titration, and ii) for succeeding dose adjustments. This requires valid models of dose/concentration relationships, but cross-sectional models suffer from population-level artefacts and individual problems due to poor adherence or stopping smoking. Longitudinal data sets from two mental health trusts allowed poor adherence and smoking cessation to be identified. We then modelled dose/concentration relationships to construct personalised targets for i) and ii).
MethodsDemographics and co-prescribed medication were recorded for 137 patients from Greater Manchester Mental Health (GMMH) Trust who had two or more successive plasma levels and doses from 2016–2018. 412 patients from Pennine Care Foundation Trust (PCFT) who had successive plasma levels and doses from 2009–2023 were also recorded. In each sample, adherent patients (88 from GMMH and 371 from PCFT) were identified after excluding: > two-fold variation between blood samples in clozapine/norclozapine ratios, > two-fold variation in dose/concentration ratios, a clozapine/norclozapine ratio > 3, or a dose/concentration ratio > two standard deviations from the sample mean. Those whose smoking status (smoker vs non-smoker) changed between samples were excluded.
To identify i) titration targets, we used raw data in first samples (checked with logistic regression) to identify dose thresholds which produced most levels above 0.35 μg/ml (therapeutic) and no levels greater than 1 μg/ml (toxic). To model ii) effective dose adjustment, we used the equation Dt = Dc(Ct/Cc) to identify the most effective dose for the second samples. Dt was target dose, Dc current dose, Ct target level (0.45 μg/ml), and Cc current level.
ResultsFirst sample dose/concentration ratio in adherent patients correlated r > 0.75 with second samples’ dose/concentration. >84% of plasma levels were within 20% of the mean across both samples.
i. The GMMH dataset titration targets were 325 mg, 300 mg, 225 mg, and 175 mg daily for male smokers, female smokers, male non-smokers, and female non-smokers, respectively. In PCFT, data suggested corresponding targets of 375 mg, 325 mg, 225 mg and 175 mg. Targets avoided toxicity and gave therapeutic levels in > 50% of cases.
ii. Target dose, ascertained using the equation, and actual second dose were compared: in adherent cases, toxicity only occurred when actual doses were 1.5-fold greater than target dose, and above target all plasma levels exceeded 0.35 μg/ml in GMMH. PCFT data appeared similar.
ConclusionRelatively safe and effective titration targets for smokers and non-smokers from both sexes were identified. A simple equation would improve precision and effectiveness of dose adjustment thereafter.
The Impact of the COVID-19 Pandemic on the Incidence of First Episode Psychosis in South London
- Zeryab Meyer, Aryn Azlan, Edoardo Spinazzola, Diego Quattrone, Robin Murray
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- Journal:
- BJPsych Open / Volume 8 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 20 June 2022, pp. S61-S62
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Aims
Transmission of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global pandemic. Many studies are underway to ascertain the mental health impact of this seismic event, however no study has investigated its effect on psychosis incidence. We hypothesise that the overall crude incidence rates of first episode psychosis (FEP) will be higher during the pandemic when comparing the same area of South London in defined pre-pandemic and pandemic time periods.
MethodsClinical records for all patients aged 18 to 64 years presenting to early intervention in psychosis services in the London boroughs of Southwark and Lambeth between July 1st 2019 to December 31st 2019 (pre-pandemic period) and July 1st 2020 to December 31st 2020 (pandemic period) were extracted from the Clinical Record Interactive Search (CRiS), an online database containing anonymised patient records. All patients were manually screened using the Screening Schedule for Psychosis to confirm FEP, with 104/235 cases meeting criteria for FEP in the pre-pandemic period compared with 158/376 in the pandemic period. Crude, age-standardised, and sex-standardised incidence rates and ratios were calculated for interpretation.
ResultsThe crude incidence rate of FEP was significantly higher in the pandemic period (68.3, 95% CI:[57.6 ; 78.9]) than the pre-pandemic period (44.9, 95% CI:[36.3 ; 53.6]). The crude incidence ratio was 1.52 (95% CI:[1.28 ; 1.77]), indicating that the overall crude incidence of FEP in the pandemic period was significantly higher (52%) than in the pre-pandemic period. The directionality and statistical significance of this ratio was unperturbed by standardisation for age (SIR = 1.45, 95% CI[1.23 ; 1.70]) and sex (SIR = 1.56, 95% CI[1.33 ; 1.83]).
ConclusionOur results suggest that the COVID-19 pandemic has had a significant impact on the incidence of FEP in the South London boroughs of Southwark and Lambeth. Further research is required to elucidate the factors contributing to this increase to inform targeted interventions and prevent deterioration in at-risk patients.
The utility of the Brief Edinburgh Depression Scale (BEDS) in assessing severity of depression in advanced cancer patients
- Zeryab Meyer, Christopher Shiels, Christopher Dowrick, Mari Lloyd-Williams
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- Journal:
- BJPsych Open / Volume 7 / Issue S1 / June 2021
- Published online by Cambridge University Press:
- 18 June 2021, p. S42
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Aims
When using an assessment tool, brevity and validity are essential. Although brief depression inventories exist, they rely heavily on the inclusion of somatic symptoms. This can be problematic in advanced cancer populations; weight loss and sleep disturbance are for the most part ubiquitous in these patients and may not necessarily be indicative of depression.
The Brief Edinburgh Depression Scale (BEDS) is a 6-item shortened version of the Edinburgh Depression Scale which has been validated for use in patients with advanced cancer and is used internationally. The BEDS cut off threshold of 6/18 indicates that depression may be present. However, the BEDS currently provides no information regarding severity. The aim of this study is to establish severity thresholds for the BEDS by comparing it to another depression scale: the commonly used, rigorously validated, Patient Health Questionnaire (PHQ-9).
Method284 advanced cancer patients attending hospice day services in the North West of England completed both the PHQ-9 and the BEDS. Mean participant age was 66.7 (Standard Deviation = 13.2) and the sample contained both males (n = 102, 36%) and females (n = 182, 64%). BEDS severity thresholds with the highest Sensitivity (Sn) and Specificity (Sp) were selected based on their ability to predict PHQ-9 categories.
ResultA BEDS score of 4 to 6 was selected to indicate ‘mild depression’ (Sn = 81.7, Sp = 65); 7 to 8 ‘moderate depression’ (Sn = 74.8, Sp = 78.7); 9 to 11 ‘moderately severe depression’ (Sn = 82, Sp = 82.9) and 12 or more ‘severe depression’ (Sn = 63.2, Sp = 92.8). A linearly weighted kappa (with s weighting) showed a moderate level of agreement (0.47, 95% Confidence Interval: 0.40-0.54).
ConclusionThe BEDS is a simple and brief tool used to screen for depression in advanced cancer patients. It is administered throughout the UK and multiple translation studies have enabled its global a (including in resource poor countries). The severity thresholds calculated here are derived from a large sample of patients with advanced cancer attending hospice services and demonstrate acceptable sensitivity and specificity in relation to the PHQ-9, a thoroughly validated reference standard. We conclude that the generated BEDS thresholds support use of the BEDS in determining the presence and severity of depression in advanced cancer populations.