RESUMO
BACKGROUND: To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust. AIMS: To investigate the impact of this temporary policy change on clinical and safety outcomes. METHOD: All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined. RESULTS: Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02-28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection. CONCLUSIONS: There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.
Assuntos
Antipsicóticos , COVID-19 , Clozapina , Neutropenia , Humanos , Clozapina/efeitos adversos , Antipsicóticos/efeitos adversos , Estudos de Coortes , Medicina Estatal , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Neutropenia/tratamento farmacológicoRESUMO
BACKGROUND: Clozapine is associated with increased risk of myocarditis. However, many common side-effects of clozapine overlap with the clinical manifestations of myocarditis. As a result, there is uncertainty about which signs, symptoms and investigations are important in distinguishing myocarditis from benign adverse effects of clozapine. Clarity on this issue is important, since missing a diagnosis of myocarditis or discontinuing clozapine unnecessarily may both have devastating consequences. AIMS: To examine the clinical characteristics of clozapine-induced myocarditis and to identify which signs and symptoms distinguish true myocarditis from other clozapine adverse effects. METHOD: A retrospective analysis of the record database for 247 621 patients was performed. A natural language processing algorithm identified the instances of patients in which myocarditis was suspected. The anonymised case notes for the patients of each suspected instance were then manually examined, and those whose instances were ambiguous were referred for an independent assessment by up to three cardiologists. Patients with suspected instances were classified as having confirmed myocarditis, myocarditis ruled out or undetermined. RESULTS: Of 254 instances in 228 patients with suspected myocarditis, 11.4% (n = 29 instances) were confirmed as probable myocarditis. Troponin and C-reactive protein (CRP) had excellent diagnostic value (area under the curve 0.975 and 0.896, respectively), whereas tachycardia was of little diagnostic value. All confirmed instances occurred within 42 days of clozapine initiation. CONCLUSIONS: Suspicion of myocarditis can lead to unnecessary discontinuation of clozapine. The 'critical period' for myocarditis emergence is the first 6 weeks, and clinical signs including tachycardia are of low specificity. Elevated CRP and troponin are the best markers for the need for further evaluation.
Assuntos
Antipsicóticos , Clozapina , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Miocardite , Antipsicóticos/efeitos adversos , Biomarcadores , Clozapina/efeitos adversos , Eletrônica , Humanos , Incidência , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Miocardite/epidemiologia , Estudos Retrospectivos , Taquicardia/induzido quimicamente , TroponinaRESUMO
BACKGROUND: Telemental health care has been rapidly adopted for maintaining services during the COVID-19 pandemic, and a substantial interest is now being devoted in its future role. Service planning and policy making for recovery from the pandemic and beyond should draw on both COVID-19 experiences and the substantial research evidence accumulated before this pandemic. OBJECTIVE: We aim to conduct an umbrella review of systematic reviews available on the literature and evidence-based guidance on telemental health, including both qualitative and quantitative literature. METHODS: Three databases were searched between January 2010 and August 2020 for systematic reviews meeting the predefined criteria. The retrieved reviews were independently screened, and those meeting the inclusion criteria were synthesized and assessed for risk of bias. Narrative synthesis was used to report these findings. RESULTS: In total, 19 systematic reviews met the inclusion criteria. A total of 15 reviews examined clinical effectiveness, 8 reported on the aspects of telemental health implementation, 10 reported on acceptability to service users and clinicians, 2 reported on cost-effectiveness, and 1 reported on guidance. Most reviews were assessed to be of low quality. The findings suggested that video-based communication could be as effective and acceptable as face-to-face formats, at least in the short term. Evidence on the extent of digital exclusion and how it can be overcome and that on some significant contexts, such as children and young people's services and inpatient settings, was found to be lacking. CONCLUSIONS: This umbrella review suggests that telemental health has the potential to be an effective and acceptable form of service delivery. However, we found limited evidence on the impact of its large-scale implementation across catchment areas. Combining previous evidence and COVID-19 experiences may allow realistic planning for the future implementation of telemental health.
Assuntos
Serviços de Saúde Mental , Telemedicina , COVID-19 , Humanos , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Early in 2020, mental health services had to rapidly shift from face-to-face models of care to delivering the majority of treatments remotely (by video or phone call or occasionally messaging) due to the COVID-19 pandemic. This resulted in several challenges for staff and patients, but also in benefits such as convenience or increased access for people with impaired mobility or in rural areas. There is a need to understand the extent and impacts of telemental health implementation, and barriers and facilitators to its effective and acceptable use. This is relevant both to future emergency adoption of telemental health and to debates on its future use in routine mental health care. OBJECTIVE: To investigate the adoption and impacts of telemental health approaches during the COVID-19 pandemic, and facilitators and barriers to optimal implementation. METHODS: Four databases (PubMed, PsycINFO, CINAHL, and Web of Science) were searched for primary research relating to remote working, mental health care, and the COVID-19 pandemic. Preprint servers were also searched. Results of studies were synthesized using framework synthesis. RESULTS: A total of 77 papers met our inclusion criteria. In most studies, the majority of contacts could be transferred to a remote form during the pandemic, and good acceptability to service users and clinicians tended to be reported, at least where the alternative to remote contacts was interrupting care. However, a range of impediments to dealing optimal care by this means were also identified. CONCLUSIONS: Implementation of telemental health allowed some continuing support to the majority of service users during the COVID-19 pandemic and has value in an emergency situation. However, not all service users can be reached by this means, and better evidence is now needed on long-term impacts on therapeutic relationships and quality of care, and on impacts on groups at risk of digital exclusion and how to mitigate these. TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews CRD42021211025; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021211025.
Assuntos
COVID-19 , Humanos , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored. AIMS: This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period. METHOD: Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication. RESULTS: Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14-1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11-1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling. CONCLUSIONS: Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.
Assuntos
Antipsicóticos , Clozapina , Transtornos Psicóticos , Esquizofrenia , Assistência ao Convalescente , Antipsicóticos/uso terapêutico , Humanos , Alta do Paciente , Prescrições , Transtornos Psicóticos/tratamento farmacológico , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológicoRESUMO
Sleep spindles are wax and waning brain oscillations at a frequency range of 11-16 Hz, lasting 0.5-2 s, that define non-rapid eye movement sleep stage 2. Over the past few years, several independent studies pointed to a decrease of sleep spindles in schizophrenia. The aim of this review is to contextualize these findings within the growing literature on these oscillations across other neuro-psychiatric disorders. Indeed, spindles reflect the coordinated activity of thalamocortical networks, and their abnormality can be observed in a variety of conditions that disrupt local or global thalamocortical connectivity. Although the broad methodological variability across studies limits the possibility of drawing firm conclusions, impaired spindling activity has been observed in several neurodevelopmental and neurodegenerative disorders. Despite such lack of specificity, schizophrenia remains the only condition with a typical late adolescence to young adulthood onset in which impaired spindling has been consistently reported. Further research is necessary to clearly define the pathogenetic mechanisms that lead to this deficit and the validity of its widespread use as a clinical biomarker.
Assuntos
Encéfalo/fisiopatologia , Esquizofrenia/fisiopatologia , Fases do Sono/fisiologia , Adolescente , Adulto , Eletroencefalografia/estatística & dados numéricos , Humanos , Adulto JovemRESUMO
BACKGROUND: Clozapine is known to cause agranulocytosis. Mandatory monitoring schemes are aimed at reducing the risk of agranulocytosis and of the consequences of agranulocytosis. All cases of agranulocytosis occurring in people prescribed clozapine are assumed to be caused by clozapine. METHODS: In a previous study, we examined a cohort of patients listed on our hospital database as having had clozapine-induced agranulocytosis and applied specific criteria to identify those with confirmed clozapine-related, life-threatening agranulocytosis. In this study, we examine the cases not meeting these specific criteria. RESULTS: In the original study, 9 of 23 cases met the criteria for clozapine-induced, life-threatening agranulocytosis. Of the 13 remaining cases for whom data were available, 5 were probably caused by clozapine but were not life-threatening. Three cases were the result of concomitant cancer chemotherapy. Three were anomalous results probably related to measurement error. For the remaining two cases, the cause was not identified. CONCLUSION: Not all cases of agranulocytosis occurring in people taking clozapine are caused by clozapine. The widely used threshold criterion-based diagnosis overestimates the risk of agranulocytosis. True clozapine-related agranulocytosis is best identified by pattern-based criteria: rapid fall in neutrophil counts over around 2 weeks to below 0.5 × 109/L for two consecutive days (unless clozapine is stopped very early or granulocyte colony stimulating factor is given) where other possible causes (benign ethnic neutropenia, cancer chemotherapy) can be ruled out.
Assuntos
Agranulocitose , Antipsicóticos , Clozapina , Neutropenia , Clozapina/efeitos adversos , Humanos , Neutropenia/induzido quimicamente , Antipsicóticos/efeitos adversos , Agranulocitose/induzido quimicamente , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
Clozapine remains the gold standard intervention for treatment-resistant schizophrenia; however, it remains underused, especially for some minority groups. A significant impediment is concern about propensity to neutropenia. The aim of this article is to provide an update on current knowledge relating to: the pattern and incidence of severe blood dyscrasias; the effectiveness of current monitoring regimes in reducing harm; the mechanisms of and the distinctions between clozapine-induced neutropenia and agranulocytosis; benign ethnic neutropenia; and changes to the monitoring thresholds in the USA and other international variations. These all have implications for the practical use of clozapine; specifically, how barriers to initiating, maintaining and restarting clozapine can be understood and in many cases overcome, especially for patients from minority groups, potentially with simpler approaches than the use of lithium or G-CSF.
RESUMO
Schizophrenia is thought to reflect aberrant connectivity within cortico-cortical and reentrant thalamo-cortical loops, which physiologically integrate and coordinate the function of multiple cortical and subcortical structures. Despite extensive research, reliable biomarkers of such "dys-connectivity" remain to be identified at the onset of psychosis, and before exposure to antipsychotic drugs. Because slow waves travel across the brain during sleep, they represent an ideal paradigm to study pathological conditions affecting brain connectivity. Here, we provide proof-of-concept evidence for a novel approach to investigate slow wave traveling properties in First-Episode Psychosis (FEP) with high-density electroencephalography (EEG). Whole-night sleep recordings of 5 drug-naïve FEP and 5 age- and gender-matched healthy control subjects were obtained with a 256-channel EEG system. One patient was re-recorded after 6 months and 3 years of continuous clozapine treatment. Slow wave detection and traveling properties were obtained with an open-source toolbox. Slow wave density and slow wave traveled distance (measured as the line of longest displacement) were significantly lower in patients (p < 0.05). In the patient who was tested longitudinally during effective clozapine treatment, slow wave density normalized, while traveling distance only partially recovered. These preliminary findings suggest that slow wave traveling could be employed in larger samples to detect cortical "dys-connectivity" at psychosis onset.
Assuntos
Clozapina , Transtornos Psicóticos , Esquizofrenia , Humanos , Eletroencefalografia , Sono/fisiologia , Esquizofrenia/tratamento farmacológicoRESUMO
Elevated hippocampal perfusion has been observed in people at clinical high risk for psychosis (CHR-P). Preclinical evidence suggests that hippocampal hyperactivity is central to the pathophysiology of psychosis, and that peripubertal treatment with diazepam can prevent the development of psychosis-relevant phenotypes. The present experimental medicine study examined whether diazepam can normalize hippocampal perfusion in CHR-P individuals. Using a randomized, double-blind, placebo-controlled, crossover design, 24 CHR-P individuals were assessed with magnetic resonance imaging (MRI) on two occasions, once following a single oral dose of diazepam (5 mg) and once following placebo. Regional cerebral blood flow (rCBF) was measured using 3D pseudo-continuous arterial spin labeling and sampled in native space using participant-specific hippocampus and subfield masks (CA1, subiculum, CA4/dentate gyrus). Twenty-two healthy controls (HC) were scanned using the same MRI acquisition sequence, but without administration of diazepam or placebo. Mixed-design ANCOVAs and linear mixed-effects models were used to examine the effects of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on rCBF in the hippocampus as a whole and by subfield. Under the placebo condition, CHR-P individuals (mean [±SD] age: 24.1 [±4.8] years, 15 F) showed significantly elevated rCBF compared to HC (mean [±SD] age: 26.5 [±5.1] years, 11 F) in the hippocampus (F(1,41) = 24.7, pFDR < 0.001) and across its subfields (all pFDR < 0.001). Following diazepam, rCBF in the hippocampus (and subfields, all pFDR < 0.001) was significantly reduced (t(69) = -5.1, pFDR < 0.001) and normalized to HC levels (F(1,41) = 0.4, pFDR = 0.204). In conclusion, diazepam normalized hippocampal hyperperfusion in CHR-P individuals, consistent with evidence implicating medial temporal GABAergic dysfunction in increased vulnerability for psychosis.
Assuntos
Circulação Cerebrovascular , Estudos Cross-Over , Diazepam , Hipocampo , Imageamento por Ressonância Magnética , Transtornos Psicóticos , Humanos , Diazepam/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/diagnóstico por imagem , Hipocampo/irrigação sanguínea , Masculino , Método Duplo-Cego , Feminino , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Adulto Jovem , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/fisiopatologia , Adulto , AdolescenteRESUMO
BACKGROUND: Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 109/L to less than 1·0 × 109/L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK. METHODS: This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration. FINDINGS: Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2-4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473). INTERPRETATION: Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health. FUNDING: None.
Assuntos
Antipsicóticos , Clozapina , Neutropenia , Transtornos Psicóticos , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Reino UnidoRESUMO
OBJECTIVE: People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI. METHODS: An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries. RESULTS: Among patients included in the study (n = 16 916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p < 0.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p < 0.001). Among AF patients having a CHA2DS2-VASc ≥2, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p < 0.001). However, there was no evidence of a significant difference between the two groups since 2019. CONCLUSION: Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population.
Assuntos
Fibrilação Atrial , Transtornos Mentais , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Hospitais Gerais , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologiaRESUMO
OBJECTIVES: This prospective cohort study tested for associations between baseline cognitive performance in individuals early within their first episode and antipsychotic treatment of psychosis. We hypothesised that poorer cognitive functioning at the initial assessment would be associated with poorer antipsychotic response following the subsequent 6 weeks. DESIGN: Prospective cohort . SETTING: National Health Service users with a first-episode schizophrenia diagnosis, recently starting antipsychotic medication, recruited from two UK sites (King's College London, UK and University of Manchester, UK). Participants attended three study visits following screening. PARTICIPANTS: Eighty-nine participants were recruited, with 46 included in the main analysis. Participants required to be within the first 2 years of illness onset, had received minimal antipsychotic treatment, have the capacity to provide consent, and be able to read and write in English. Participants were excluded if they met remission criteria or showed mild to no symptoms. PRIMARY AND SECONDARY OUTCOME MEASURES: Antipsychotic response was determined at 6 weeks using the Positive and Negative Syndrome Scale (PANSS), with cognitive performance assessed at each visit using the Brief Assessment of Cognition in Schizophrenia (BACS). The groups identified (responders and non-responders) from trajectory analyses, as well as from >20% PANSS criteria, were compared on baseline BACS performance. RESULTS: Trajectory analyses identified 84.78% of the sample as treatment responsive, and the remaining 15.22% as treatment non-responsive. Unadjusted and adjusted logistic regressions observed no significant relationship between baseline BACS on subscale and total performance (BACS t-score: OR=0.98, p=0.620, Cohen's d=0.218) and antipsychotic response at 6 weeks. CONCLUSIONS: This investigation identified two clear trajectories of treatment response in the first 6 weeks of antipsychotic treatment. Responder and non-responder groups did not significantly differ on performance on the BACS, suggesting that larger samples may be required or that an association between cognitive performance and antipsychotic response is not observable in the first 2 years of illness onset. TRIAL REGISTRATION NUMBER: REC: 17/NI/0209.
Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Esquizofrenia/complicações , Antipsicóticos/uso terapêutico , Estudos Prospectivos , Medicina Estatal , Cognição/fisiologia , Estudos de CoortesRESUMO
BACKGROUND: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. AIM: This study investigates sociodemographic and clinical correlates of early onset of TRS. METHOD: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. RESULTS: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). CONCLUSION: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.
Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Masculino , Humanos , Feminino , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/diagnóstico , Estudos Retrospectivos , Atividades Cotidianas , Alucinações/tratamento farmacológico , Clozapina/uso terapêuticoRESUMO
OBJECTIVES: To develop a prognostic tool of treatment resistant schizophrenia (TRS) in a large and diverse clinical cohort, with comprehensive coverage of patients using mental health services in four London boroughs. METHODS: We used the Least Absolute Shrinkage and Selection Operator (LASSO) for time-to-event data, to develop a risk prediction model from the first antipsychotic prescription to the development of TRS, using data from electronic health records. RESULTS: We reviewed the clinical records of 1,515 patients with a schizophrenia spectrum disorder and observed that 253 (17%) developed TRS. The Cox LASSO survival model produced an internally validated Harrel's C index of 0.60. A Kaplan-Meier curve indicated that the hazard of developing TRS remained constant over the observation period. Predictors of TRS were: having more inpatient days in the three months before and after the first antipsychotic, more community face-to-face clinical contact in the three months before the first antipsychotic, minor cognitive problems, and younger age at the time of the first antipsychotic. CONCLUSIONS: Routinely collected information, readily available at the start of treatment, gives some indication of TRS but is unlikely to be adequate alone. These results provide further evidence that earlier onset is a risk factor for TRS.
Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Estudos de Coortes , Registros Eletrônicos de Saúde , Humanos , Modelos de Riscos Proporcionais , Esquizofrenia/tratamento farmacológicoRESUMO
BACKGROUND: A proportion of people with treatment-resistant schizophrenia fail to show improvement on clozapine treatment. Knowledge of the sociodemographic and clinical factors predicting clozapine response may be useful in developing personalised approaches to treatment. METHODS: This retrospective cohort study used data from the electronic health records of the South London and Maudsley (SLaM) hospital between 2007 and 2011. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression statistical learning approach, we examined 35 sociodemographic and clinical factors' predictive ability of response to clozapine at 3 months of treatment. Response was assessed by the level of change in the severity of the symptoms using the Clinical Global Impression (CGI) scale. RESULTS: We identified 242 service-users with a treatment-resistant psychotic disorder who had their first trial of clozapine and continued the treatment for at least 3 months. The LASSO regression identified three predictors of response to clozapine: higher severity of illness at baseline, female gender and having a comorbid mood disorder. These factors are estimated to explain 18% of the variance in clozapine response. The model's optimism-corrected calibration slope was 1.37, suggesting that the model will underfit when applied to new data. CONCLUSIONS: These findings suggest that women, people with a comorbid mood disorder and those who are most ill at baseline respond better to clozapine. However, the accuracy of the internally validated and recalibrated model was low. Therefore, future research should indicate whether a prediction model developed by including routinely collected data, in combination with biological information, presents adequate predictive ability to be applied in clinical settings.
Assuntos
Antipsicóticos , Clozapina , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Estudos Retrospectivos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológicoRESUMO
Disturbances of conscious awareness, or self-disorders, are a defining feature of schizophrenia. These include symptoms such as delusions of control, i.e. the belief that one's actions are controlled by an external agent. Models of self-disorders point at altered neural mechanisms of source monitoring, i.e. the ability of the brain to discriminate self-generated stimuli from those driven by the environment. However, evidence supporting this putative relationship is currently lacking. We performed electroencephalography (EEG) during self-paced, brisk right fist closures in ten (M = 9; F = 1) patients with Early-Course Schizophrenia (ECSCZ) and age and gender-matched healthy volunteers. We measured the Readiness Potential (RP), i.e. an EEG feature preceding self-generated movements, and movement-related EEG spectral changes. Self-disorders in ECSCZ were assessed with the Examination of Anomalous Self-Experience (EASE). Patients showed a markedly reduced RP and altered post-movement Event-Related Synchronization (ERS) in the beta frequency band (14-24 Hz) compared to healthy controls. Importantly, smaller RP and weaker ERS were associated with higher EASE scores in ECSCZ. Our data suggest that disturbances of neural correlates preceding and following self-initiated movements may reflect the severity of self-disorders in patients suffering from ECSCZ. These findings point towards deficits in basic mechanisms of sensorimotor integration as a substrate for self-disorders.