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1.
Encephale ; 46(3S): S126-S127, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32475694
2.
PLoS One ; 15(6): e0234864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555706

RESUMO

The purpose of this study was to develop the Glasgow Antipsychotic Side effects Scale for Clozapine Japanese version (GASS-C-J) and examine its reliability to assess clozapine-related side effects. We developed the GASS-C-J using forward and backward translation. Semantic equivalence of the GASS-C-J to the GASS-C was confirmed by the original author. We then administered the GASS-C-J twice to 109 patients on clozapine treatment at two psychiatric hospitals in Japan. We assessed the internal consistency and test-retest reliability of the GASS-C-J using Cronbach's alpha and weighted kappa coefficient, respectively. We also examined if discrepancies in each GASS-C-J item score between the first and second rating were correlated with items of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD). The Cronbach's alpha coefficient of the GASS-C-J at the first and second rating was 0.78 (95% CI: 0.72 to 0.84) and 0.82 (95% CI: 0.76 to 0.88), respectively. The weighted kappa coefficient of individual and total GASS-C-J item scores ranged from 0.45 to 0.88. Some symptom domains were correlated with discrepancies in specific items of the GASS-C-J: psychotic symptoms and nausea/vomiting (rs = 0.27), thirst (rs = 0.31), and appetite/weight gain (rs = 0.27); disorganized thinking and urinary incontinence (rs = 0.26); depression/anxiety and myoclonus (rs = 0.25), hypersalivation (rs = -0.27), and blurred vision (rs = -0.22). These findings demonstrate that the GASS-C-J can be used in clinical and research settings as a reliable scale to assess clozapine-related side effects.


Assuntos
Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Escala de Resultado de Glasgow/normas , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/sangue , Antipsicóticos/uso terapêutico , Clozapina/sangue , Clozapina/uso terapêutico , Estudos Transversais , Resistência a Medicamentos/efeitos dos fármacos , Feminino , Hospitais Psiquiátricos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários
3.
Brasília; s.n; 20 jun. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1102288

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos e 9 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Vacinas/isolamento & purificação , Heparina/uso terapêutico , Cloroquina/uso terapêutico , Clozapina/uso terapêutico , Ritonavir/uso terapêutico , Lopinavir/uso terapêutico , Fibrinolíticos/uso terapêutico , Hidroxicloroquina/uso terapêutico
4.
Fortschr Neurol Psychiatr ; 88(8): 495-499, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32392585

RESUMO

We report four cases of 12- to 17-year-old patients with schizophrenia, two of them suffering from catatonia, which were treated by ECT. Under a combined treatment with either ziprasidone or clozapine, and electroconvulsive therapy (ECT), they improved markedly. Severity and course of acute schizophrenia were evaluated by the Brief Psychiatric rating Scale (BPRS), severity and course of catatonia were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This article underlines the benefit, the safety and the tolerability of ECT in younger patients with schizophrenic disorders.


Assuntos
Eletroconvulsoterapia , Esquizofrenia/terapia , Adolescente , Catatonia/complicações , Criança , Clozapina/uso terapêutico , Terapia Combinada , Humanos , Piperazinas/uso terapêutico , Esquizofrenia/complicações , Tiazóis/uso terapêutico , Resultado do Tratamento
11.
Life Sci ; 249: 117535, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32151688

RESUMO

AIM: Schizophrenia is a chronic, disabling and one of the major neurological illnesses affecting nearly 1% of the global population. Currently available antipsychotic medications possess limited effects. The current research aimed at investigating potential therapeutic add-on benefit to enhance the effects of clozapine anti-schizophrenic. MAIN METHODS: To induce schizophrenia, ketamine was administered at a dose of 25 mg/kg i.p. for 14 consecutive days. Naringin was administered to Wistar rats at a dose of 100 mg/kg orally, alone or in combination with clozapine 5 mg/kg i.p from day 8 to day 14. Furthermore, behavioral tests were conducted to evaluate positive, negative and cognitive symptoms of schizophrenia. In addition, neurotransmitters' levels were detected using HPLC. Moreover, oxidative stress markers were assessed using spectrophotometry. Furthermore, apoptotic and wnt/ß-catenin pathway markers were determined using western blotting (Akt, GSK-3ß and ß-catenin), colorimetric methods (Caspase-3) and immunohistochemistry (Bax, Bcl2 and cytochrome c). KEY FINDINGS: Ketamine induced positive, negative and cognitive schizophrenia symptoms together with neurotransmitters' imbalance. In addition, ketamine treatment caused significant glutathione depletion, lipid peroxidation and reduction in catalase activity. Naringin and/or clozapine treatment significantly attenuated ketamine-induced schizophrenic symptoms and oxidative injury. Additionally, ketamine provoked apoptosis via increasing Bax/Bcl2 expression, caspase-3 activity, and Cytochrome C and Akt protein expression while naringin/clozapine treatment significantly inhibited this apoptotic effect. Moreover, naringin activated the neurodevelopmental wnt/ß-catenin signaling pathway evidenced by increasing pGSK-3ß and reducing pß-catenin protein expression. SIGNIFICANCE: These findings may suggest that naringin possesses a potential therapeutic add-on effect against ketamine-induced schizophrenia.


Assuntos
Antipsicóticos/farmacologia , Flavanonas/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Ketamina/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Esquizofrenia/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Clozapina/administração & dosagem , Clozapina/farmacologia , Clozapina/uso terapêutico , Modelos Animais de Doenças , Flavanonas/administração & dosagem , Flavanonas/uso terapêutico , Masculino , Ratos , Ratos Wistar , Esquizofrenia/induzido quimicamente
12.
J Clin Pathol ; 73(9): 587-592, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32094276

RESUMO

AIMS: An association between antibody deficiency and clozapine use in individuals with schizophrenia has recently been reported. We hypothesised that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns. METHODS: Retrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunological features for individuals with diagnosis of schizophrenia-like illness. RESULTS: 1791 adult patients were assessed at ICW during this period; 23 patients had a psychiatric diagnosis of schizophrenia or schizoaffective disorder. Principal indications for referral were findings of low calculated globulin and immunoglobulins. Clozapine was the single most commonly prescribed antipsychotic (17/23), disproportionately increased relative to reported use in the general schizophrenia population (OR 6.48, 95% CI: 1.79 to 23.5). Clozapine therapy was noted in 6/7 (86%) of patients subsequently requiring immunoglobulin replacement therapy (IgRT). Marked reduction of class-switched memory B cells (CSMB) and plasmablasts were observed in clozapine-treated individuals relative to healthy age-matched controls. Clozapine duration is associated with CSMB decline. One patient discontinued clozapine, with gradual recovery of IgG levels without use of IgRT. CONCLUSIONS: Our findings are consistent with enrichment of clozapine-treatment within schizophrenic individuals referred for ICW assessment over the last 13 years. These individuals displayed clinical patterns closely resembling the primary immunodeficiency common variable immunodeficiency, however appears reversible on drug cessation. This has diagnostic, monitoring and treatment implications for psychiatry and immunology teams and directs prospective studies to address causality and the wider implications for this patient group.


Assuntos
Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Síndromes de Imunodeficiência/patologia , Esquizofrenia/patologia , Linfócitos B/patologia , Imunodeficiência de Variável Comum , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/tratamento farmacológico , Estudos Retrospectivos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico
13.
Nervenarzt ; 91(2): 107-113, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31989210

RESUMO

BACKGROUND: The development of delirium in patients with idiopathic Parkinson's disease (IPD) is a feared complication, which is often associated with sustained worsening of motor symptoms and psychopathological sequelae. Little is known regarding the prevalence and incidence rates, course and prognosis. Clinical studies from which recommendations for evidence-based management of delirium in IPD can be derived are lacking. OBJECTIVE: To summarize the state of the art regarding epidemiological and clinical features of delirium in IPD. Discussion of prevention strategies and non-pharmacological and pharmacological treatment options. METHODS: A literature search was carried out in PubMed. RESULTS: The IPD is an independent risk factor for the development of delirium. Patients with IPD show poorer clinical outcome frequently with cognitive worsening and motor complications following development of delirium. CONCLUSION: So far no validated rating scales for recognition and course evaluation of delirium in IPD are available. Preventive strategies and non-pharmacological measures should be consistently implemented to improve management. There are insufficient data concerning pharmacotherapy with quetiapine and clozapine, whereas other neuroleptics are contraindicated for delirium in IPD due to antidopaminergic side effects.


Assuntos
Antipsicóticos , Clozapina , Delírio , Doença de Parkinson , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Delírio/tratamento farmacológico , Delírio/etiologia , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Fatores de Risco
14.
Nervenarzt ; 91(1): 34-42, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31919550

RESUMO

BACKGROUND: Schizophrenia is a severe psychiatric disorder with variable therapeutic responses, the etiology and pathophysiology of which require further elucidation. OBJECTIVE: To review which pharmacological options are effective and safe and for which treatment goals in schizophrenia. MATERIAL AND METHODS: Narrative review of the pharmacological therapy of adults diagnosed with schizophrenia. RESULTS: Despite heterogeneous therapeutic responses, to date only dopamine antagonists or partial agonists are approved for the treatment of schizophrenia. The efficacy of antipsychotic agents differs only gradually, with the exception of clozapine for treatment-resistant schizophrenia, whereas undesired adverse effects are more variable. Those antipsychotic agents that show gradual efficacy advantages in meta-analyses of acute and maintenance treatment (clozapine, amisulpride, olanzapine, risperidone) are also those where at least one undesired adverse effect is most severely expressed. Antipsychotic adverse effects occur in subgroups of patients and are generally tolerable or treatable, whereas the "side effect" of untreated schizophrenia affects almost all patients, including relapses, psychosocial deterioration, secondary treatment resistance and increased mortality. Therefore, in patients with a confirmed diagnosis of schizophrenia, a lifelong continuous therapy is currently most likely indicated, ideally with antipsychotic agents for which adherence is directly measurable and improved. In the case of treatment resistant clozapine is the agent of choice, followed by electroconvulsive therapy, which also has the best evidence as augmentation treatment in cases of clozapine resistance. CONCLUSION: New therapeutic agents with improved efficacy and tolerability as well as effectiveness for negative symptoms and cognitive disturbance are needed.


Assuntos
Antipsicóticos , Esquizofrenia , Adulto , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Humanos , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
15.
Biomed Res Int ; 2020: 9872936, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998804

RESUMO

Background and Objective: Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models. Methods: A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded. Results: Twelve studies were included in this review. Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models. Conclusions: Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.


Assuntos
Antipsicóticos , Clozapina , Citocromo P-450 CYP1A2/metabolismo , Modelos Biológicos , Esquizofrenia , Adulto , Antipsicóticos/farmacocinética , Antipsicóticos/uso terapêutico , Clozapina/farmacocinética , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Esquizofrenia/patologia
16.
Curr Top Behav Neurosci ; 44: 227-244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30993585

RESUMO

In recent years, there is a new optimism in schizophrenia therapeutics with the emergence of immunomodulation as a potential treatment approach. Current evidence points to various immunological abnormalities in schizophrenia, including cell-mediated processes, acute phase proteins, cytokines, and intracellular mediators. Trait- and state-related immune dysfunction appears to exist, and a strong case can therefore be made for immunomodulation therapies in the prevention, treatment, and/or moderating the course of schizophrenia.Immunomodulation approaches include use of nonsteroidal anti-inflammatory agents to stop or moderate an over-activated inflammatory process, anti-oxidants, nutrients, vitamins, herbal products, and other neuroprotection agents that inhibit pro-inflammatory processes, optimal use of antipsychotic drugs (APDs) that may have anti-inflammatory actions or in certain cases such as clozapine may enhance blunted inflammatory responses, and biological agents to antagonize specific immune mediators such as the cytokines. A combination of two or more of the above approaches is also worthy of consideration.In this chapter, the available data for each of the above approaches is reviewed and discussed. Strengths and limitations of current studies are identified, and suggestions are made for future studies. For example, identifying patients with high levels of specific biomarkers such as C-Reactive Protein, IL-6, IFN-γ, TNF-α, and genetic polymorphisms of cytokines, and match them with clinical subgroups such as prodromal, first episode psychosis, chronic psychosis, and negative symptoms with the aim of developing targeted treatment approaches and more personalized medicine. Meanwhile, since the science and trial data are not advanced enough to make definitive recommendations, clinicians should stay up to date with the literature, obtain detailed immunological histories, and review the risk-benefit ratio of adding available immune modulating agents to standard therapies, to provide optimal and state-of-the-art care to patients.


Assuntos
Antipsicóticos , Clozapina , Inflamação , Esquizofrenia , Anti-Inflamatórios/uso terapêutico , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Citocinas , Humanos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/imunologia
17.
Int Clin Psychopharmacol ; 35(1): 36-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31714320

RESUMO

Reports of decreased mortality among patients with schizophrenia who use clozapine may be biased if clozapine is prescribed to relatively healthy patients and if intensive monitoring during its use prevents (under-treatment of) somatic disorder. We aimed to assess whether there is a difference in: (1) somatic comorbidity between patients who start with clozapine and those who start with other antipsychotics and (2) prescribed somatic medication, between patients using clozapine and those using olanzapine. Cohort study based on insurance claims (2010-2015). After selecting new users of antipsychotics and those who subsequently switched to clozapine (N = 158), aripiprazole (N = 295), olanzapine (N = 204) or first-generation antipsychotics (N = 295), we compared the clozapine starters to others on cardiovascular or diabetic comorbidity. Those using clozapine and olanzapine were compared on new prescriptions for cardiovascular or antidiabetic drugs. The ORadj of cardiovascular or diabetic comorbidity among other starters compared with clozapine starters was 0.77 [95% confidence interval (CI): 0.43-1.39], that is, a nonsignificantly increased prevalence associated with clozapine was found. Users of clozapine received significantly more new prescriptions for cardiovascular or antidiabetic medication (ORadj: 2.70, 95% CI: 1.43-5.08). Starters with clozapine were not cardiovascular/metabolic healthier than starters with other antipsychotics. During its use, they received more somatic treatment.


Assuntos
Antipsicóticos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Clozapina/uso terapêutico , Diabetes Mellitus/epidemiologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Idoso , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Clozapina/administração & dosagem , Clozapina/efeitos adversos , Diabetes Mellitus/tratamento farmacológico , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Nível de Saúde , Humanos , Hipoglicemiantes/uso terapêutico , Revisão da Utilização de Seguros , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia
19.
Ir J Psychol Med ; 36(4): 239-241, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31747989

RESUMO

Psychotic disorders are central to mental health service provision and a common theme of academic research programmes in Ireland, which explore the neurobiological and psychosocial risk factors underpinning the development and progression of these illnesses. While we await the discovery of novel pharmacological treatment targets for psychotic disorders, it is important to employ our existing management strategies to optimal effect. In this special issue on psychosis, a selection of clinical research studies and reviews from Irish researchers, and often of Irish populations, are brought together which span the trajectory of psychotic illness from early intervention to treatment resistance. The topics include the characteristics and course of first episode psychosis cohorts, real-world evaluation of early intervention services, management strategies for treatment resistant schizophrenia and neurobiological research into social stress. The current editorial provides an overview of these papers and highlights the initial steps of the Irish Psychosis Research Network towards developing an integrated clinical research network focusing on the treatment and research into psychotic disorders.


Assuntos
Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Transtornos Psicóticos/terapia , Esquizofrenia/terapia , Resistência a Medicamentos/fisiologia , Intervenção Educacional Precoce , Humanos , Irlanda/epidemiologia , Serviços de Saúde Mental/normas , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/fisiopatologia , Fatores de Risco , Resultado do Tratamento
20.
Ir J Psychol Med ; 36(4): 259-263, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31747990

RESUMO

BACKGROUND: Clozapine is an atypical antipsychotic agent used primarily in the management of treatment-resistant schizophrenia. Previous studies have demonstrated clozapine's superior efficacy over other antipsychotic medications in treating this population of patients. The aim of this study was to assess if the number of hospital admissions and days spent in hospital reduced with the initiation of clozapine, compared with when the same sample of patients were prescribed other antipsychotics prior to clozapine initiation. METHOD: A mirror-image study design was adopted. In this case the intervention under study was the initiation of clozapine. Information was collected retrospectively from the charts of patients attending the University Hospital Galway clozapine clinic. The number of admissions and number of hospital days were collected for each patient over the 3 years before and after clozapine initiation. Wilcoxon's signed-rank test was used to test for statistical significance. RESULTS: The total sample size comprised of 62 patients, of which the majority were male (74.2%) and had a diagnosis of schizophrenia (82.3%). The mean dose of clozapine was 417 mg, and mean age of the sample was 38 years. Mean number of hospital admissions reduced from 2.8 to 0.8 (p<0.0001) following initiation of clozapine. Mean number of days spent in hospital reduced from 116.4 to 17.1 (p<0.0001). CONCLUSION: After initiation of clozapine treatment, patients experience a substantial reduction in number of hospital admissions and number of days spent in hospital when compared with a similar period prior to clozapine initiation.


Assuntos
Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Substituição de Medicamentos/efeitos adversos , Hospitalização/estatística & dados numéricos , Adulto , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Resistência a Medicamentos , Feminino , Hospitalização/tendências , Hospitais Psiquiátricos/estatística & dados numéricos , Hospitais Psiquiátricos/tendências , Humanos , Masculino , Estudos Retrospectivos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento
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