A Covid-19 outbreak in a Spanish long-term psychiatric hospital led to infections in 6 clozapine patients: elevations in their plasma clozapine levels.
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SUBMITTER: Arrojo-Romero M
PROVIDER: S-EPMC9734288 | biostudies-literature | 2022 Oct-Dec
REPOSITORIES: biostudies-literature
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A Covid-19 outbreak in a Spanish long-term psychiatric hospital led to infections in 6 clozapine patients: elevations in their plasma clozapine levels.
Arrojo-Romero Manuel M Codesido-Barcala Maria Rosario MR de Leon Jose J
Revista de psiquiatria y salud mental 20221001 4
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Project description: Not available
| S-EPMC9233870 | biostudies-literature
Project description:Aims and methodTo compare differences in clozapine doses and plasma levels between Bangladeshi and White British patients. Following ethical approval we identified all current Bangladeshi and White British patients on clozapine maintenance in an east London clinic. We carried out univariate and multivariate regression analyses to examine associations between clozapine doses and ethnicity, age, gender, smoking status and weight. We also compared plasma clozapine levels of the two groups.ResultsOn univariate analysis White British patients had on average 85 mg higher doses than Bangladeshi patients (P = 0.004). Older age, male gender and smoking were also associated with higher dose. On multivariate analysis only age and smoking status remained significant. A greater proportion of Bangladeshi patients had high plasma clozapine levels compared with White British (30.76% v. 20.75%), although the difference was not statistically significant.Clinical implicationsOur findings point to the need for the broadening of data collection on ethnic differences in clozapine prescribing within big data-sets such as Prescribing Observatory for Mental Health (POM-UK). Ethnopharmacological variations can inform more person-centred guidance on prescribing.
| S-EPMC8058897 | biostudies-literature
Project description:Clozapine is the sole antipsychotic agent effective for the treatment of refractory schizophrenia. Sixty percent of clozapine-treated patients, however, fail to adequately respond. Minocycline, a tetracycline antibiotic, possesses antiinflammatory and neuroprotective properties that may play a role in schizophrenia. Clozapine is mainly metabolized by CYP1A2 enzymes, and minocycline may potentially inhibit CYP1A2 as hypothesized by case report data. To date, no pharmacokinetic interaction has been reported between minocycline and clozapine. This is a secondary analysis of a 10-week controlled study of adjunctive minocycline to clozapine in treatment refractory schizophrenia. Clozapine plasma levels were collected every two weeks during the study. 28 participants assigned to receive minocycline and 22 assigned to placebo were included. No differences existed in baseline demographics, clozapine dose or plasma levels. Average changes from baseline in clozapine plasma level (p = 0.033) were significantly higher in the minocycline group despite maintenance of stable doses. No statistically significant treatment differences were found in the norclozapine (p = 0.754) or total clozapine (p = 0.053) changes in plasma levels, although possible changes in total clozapine levels require further investigation. This analysis suggests that minocycline administration may lead to increased clozapine plasma levels. Further study is needed to examine possible explanations.
| S-EPMC5670021 | biostudies-literature
Project description:BackgroundThe demand for urgent psychiatric care is increasing, but in Spain there are no clear recommendations for emergency departments (ED) on how to optimize care for patients with psychiatric emergencies. We aimed to provide expert consensus recommendations on the requirements for general hospitals´ emergency departments to treat patients with urgent psychiatric symptoms.MethodsWe used a modified Delphi technique. A scientific committee compiled 36 statements based on literature search and clinical experience. The statements covered the organizational model, facilities, staffing, safety, patient interventions, and staff training. A panel of 38 psychiatry specialists with expertise in psychiatric emergencies evaluated the questionnaire in two rounds.ResultsAfter two rounds of voting, 30 out of 36 proposed items (83%) were agreed upon. The panel agreed that psychiatric emergencies should be managed in a general hospital, with dedicated facilities for patient assessment, direct supervision of patients at risk, and an observation unit run by the psychiatric service. In addition to the psychiatrist, the ED should have specialist nurses and security staff available 24/7. Social workers should also be readily available. ED and consulting rooms should be designed to ensure patient and staff safety. A triage system should be established for patients with psychiatric symptoms, with medical evaluation preceding psychiatric evaluation. Guidance on supplies, equipment, and staff training is also provided.ConclusionAll ED in general hospitals should have adequate resources to handle any psychiatric emergency. This paper provides recommendations on the minimum requirements to achieve this goal.
| S-EPMC11225242 | biostudies-literature
Project description:Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.
| S-EPMC9317288 | biostudies-literature
Project description:The prevalence of infections is supposed to be higher in older patients and to extend the length of hospital stays. This study aimed, first, to test this supposition within a large psychiatric population which we divided into four clusters of psychiatric ICD-10 diagnoses: F00-F03 (dementias), F10 (substance disorders), F20-29 (schizophrenia, schizophreniform and other non-mood psychotic disorders), F32-F33 (major depressive disorders). Second, despite the increasing evidence for the role of infections in psychiatric disorders, it is, to the best of our knowledge, largely unknown whether the rates of infections with pathogens of the four most frequent germ families differ between psychiatric diseases. Thus, in a retrospective study, the results of clinical routine examinations (pap smear, analysis of midstream urine, stool) dependent on symptoms in 8545 patients of a German psychiatric clinic were analyzed in a 12-year dataset. Results show that a longer hospital stay was associated with an increased number of microbiological tests, but led to no significant difference between positive vs. negative findings. Consistent with previous studies, patients with infections were older than patients without infections. For the F10 diagnosis cluster we found a significantly reduced (F10: Staphylococcaceae) and for the F20-29 cluster a heightened risk of infections (Staphylococcaceae, Corynebacteriaceae). Furthermore, patients belonging to the F00-F03 cluster exhibited elevated rates of infections with all four germ families. The latter can be ascribed to patients' age as we found higher age to be associated with these infections, independently of the presence of dementia. Our results suggest that different psychiatric diagnoses are associated with a heightened or lowered risk of bacterial infections and, furthermore, that clinical routine infection-screenings for elderly psychiatric patients seems to be reasonable.
| S-EPMC6279031 | biostudies-literature
Project description:PurposePsychiatric emergency hospital admissions for distinct psychiatric disorders and length of inpatient stay in the hospital during the Coronavirus disease 2019 (COVID-19) outbreak have not been thoroughly assessed.MethodsA retrospective study was performed analyzing claims data from a large German Hospital network during the COVID-19 outbreak (study period: March 13-May 21, 2020) as compared to periods directly before the outbreak (same year control: January 1-March 12, 2020) and one year earlier (previous year control: March 13-May 21, 2019).ResultsA total of 13,151 emergency hospital admissions for psychiatric diagnoses were included in the analysis. For all psychiatric diagnoses combined, emergency admissions significantly decreased during the study period with mean (interquartile range) incidence rate ratios (IRRs) of 0.68 (0.65, 0.71) and 0.70 (0.67, 0.73) as compared to the same and previous year controls, respectively (both p < 0.00001). IRR ranged from 0.56 for mood affective disorders (F30-F39) to 0.75 for mental disorders due to psychoactive substance use (F10-F19; all p < 0.00001). Mean (standard deviation) length of hospital stay for all psychiatric diagnoses was significantly shorter during the study period [9.8 (11.6) days] as compared to same [14.7 (18.7) days] and previous [16.4 (23.9) days] year controls (both p < 0.00001).ConclusionBoth emergency hospital admissions and length of hospital stay significantly decreased for psychiatric disorders during the COVID-19 outbreak. It needs to be assessed in further studies whether healthcare systems will face increased demand for the provision of mental health care in the nearer future.
| S-EPMC8053025 | biostudies-literature
Project description:BackgroundSome schizophrenia patients treated with clozapine experience an inadequate response and adherence problems. The purpose of this study was to compare time to rehospitalization within 6 months in schizophrenia patients discharged on 3 clozapine regimens. Additionally, the temporal trend of prescription rate in each group was also explored.MethodsSchizophrenia patients discharged from the study hospital from January 1, 2006, to December 31, 2021, (n = 3271) were included in the analysis. The type of clozapine prescribed at discharge was divided into 3 groups: clozapine plus long-acting injectable antipsychotics (clozapine + LAIs), clozapine plus other oral antipsychotics (clozapine + OAPs), and clozapine monotherapy. Survival analysis was used to compare time to rehospitalization within 6 months after discharge among the 3 groups. The temporal trend in the prescription rate of each group was analyzed using the Cochran-Armitage Trend test.ResultsPatients discharged on clozapine + LAIs had a significantly longer time to rehospitalization than those on clozapine + OAPs or clozapine monotherapy. The prescription rates of clozapine + LAIs and clozapine + OAPs significantly increased over time, whereas the prescription rates of clozapine monotherapy significantly decreased.ConclusionsCompared with the clozapine + OAPs group, the clozapine + LAIs group had a lower risk of rehospitalization and a lower dose of clozapine prescribed. Therefore, if a second antipsychotic is required for patients who are taking clozapine alone, LAIs should be considered earlier.
| S-EPMC10674076 | biostudies-literature
Project description:BackgroundSoluble suppression of tumorigenicity 2 (sST2), a decoy receptor for interleukin (IL)-33, has emerged as a novel biomarker in various disease processes. Recent studies have elucidated the role of the sST2/IL-33 complex in modulating the balance of Th1/Th2 immune responses after tissue stress. However, the role of sST2 as a biomarker after traumatic injury remains unclear. To address this, we evaluated serum sST2 correlations with mortality and in-hospital adverse outcomes as endpoints in blunt trauma patients.MethodsWe retrospectively analyzed clinical and biobank data of 493 blunt trauma victims 472 survivors (mean age: 48.4 ± 0.87; injury severity score [ISS]: 19.6 ± 0.48) and 19 nonsurvivors (mean age: 58.8 ± 4.5; ISS: 23.3 ± 2.1) admitted to the intensive care unit. Given the confounding impact of age on the inflammatory response, we derived a propensity-matched survivor subgroup (n = 19; mean age: 59 ± 3; ISS: 23.4 ± 2) using an IBM SPSS case-control matching algorithm. Serial blood samples were obtained from all patients (3 samples within the first 24 h and then once daily from day [D] 1 to D5 after injury). sST2 and twenty-nine inflammatory biomarkers were assayed using enzyme-linked immunosorbent assay and Luminex, respectively. Two-way analysis of variance on ranks was used to compare groups (P < 0.05). Spearman rank correlation was performed to determine the association of circulating sST2 levels with biomarker levels and in-hospital clinical outcomes.ResultsCirculating sST2 levels of the nonsurvivor cohort were statistically significantly elevated at 12 h after injury and remained elevated up to D5 when compared either to the overall 472 survivor cohort or a matched 19 survivor subcohort. Admission sST2 levels obtained from the first blood draw after injury in the survivor cohort correlated positively with admission base deficit (correlation coefficient [CC] = 0.1; P = 0.02), international normalized ratio (CC = 0.1, P = 0.03), ISS (CC = 0.1, P = 0.008), and the average Marshall multiple organ dysfunction score between D2 and D5 (CC = 0.1, P = 0.04). Correlations with ISS revealed a positive correlation of ISS with plasma sST2 levels across the mild ISS (CC = 0.47, P < 0.001), moderate ISS (CC = 0.58, P < 0.001), and severe ISS groups (CC = 0.63, P < 0.001). Analysis of biomarker correlations in the matched survivor group over the initial 24 h after injury showed that sST2 correlates strongly and positively with IL-4 (CC = 0.65, P = 0.002), IL-5 (CC = 0.57, P = 0.01), IL-21 (CC = 0.52, P = 0.02), IL-2 (CC = 0.51, P = 0.02), soluble IL-2 receptor-α (CC = 0.5, P = 0.02), IL-13 (CC = 0.49, P = 0.02), and IL-17A (CC = 0.48, P = 0.03). This was not seen in the matched nonsurvivor group. sST2/IL-33 ratios were significantly elevated in nonsurvivors and patients with severe injury based on ISS ≥ 25.ConclusionsElevations in serum sST2 levels are associated with poor clinical trajectories and mortality after blunt trauma. High sST2 coupled with low IL-33 associates with severe injury, mortality, and worse clinical outcomes. These findings suggest that sST2 could serve as an early prognostic biomarker in trauma patients and that sustained elevations of sST2 could contribute to a detrimental suppression of IL-33 bioavailability in patients with high injury severity.
| S-EPMC6815699 | biostudies-literature