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1.
Nihon Yakurigaku Zasshi ; 154(5): 275-287, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735758

RESUMO

Brexpiprazole (Rexulti®) is the second antipsychotic agent in the world with dopamine D2 receptor partial agonist which was developed by Otsuka Pharmaceutical Co. Ltd. It is categorized as 〝Serotonin- dopamine Activity Modulator (SDAM)〟 that regulates both serotoninergic and dopaminergic systems by acting as a partial agonist for serotonin 5-HT1A receptors and D2 receptors and as an antagonist for 5-HT2A receptors. In preclinical pharmacological studies, brexpiprazole showed the equivalent antipsychotic-like effects to those of other atypical antipsychotics. And it was suggested that brexpiprazole has the low potentials to induce extrapyramidal symptoms, hyperprolactinemia and tardive dyskinesia, with improvement effects on cognitive dysfunction. Furthermore, brexpiprazole has the weak effects on histamine H1 receptors which are associated with sedation and weight gain in clinical. In the clinical trials in patients with schizophrenia in both acute and maintenance phase, brexpiprazole showed improvement of antipsychotic effects against placebo, and low incidence of adverse events, e.g., extrapyramidal symptoms, hyperprolactinemia, and weight gain, as suggested in preclinical studies. Furthermore, brexpiprazole showed low incidence of metabolic abnormalities. In particular, brexpiprazole showed relatively low incidences of akathisia, insomnia and agitation which has been commonly reported with aripiprazole. This would be based on the pharmacological features of brexpiprazole that is more potent antagonism at 5-HT2A receptors and D2 receptors partial agonism with lower intrinsic activity compared to those of aripiprazole. In conclusion, brexpiprazole could be one of the antipsychotics with the most rational mechanism of action, and the better efficacy and safety/tolerability profiles would contribute to the treatment of patients with schizophrenia.


Assuntos
Antipsicóticos/farmacologia , Quinolonas/farmacologia , Tiofenos/farmacologia , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Esquizofrenia/tratamento farmacológico , Comprimidos , Resultado do Tratamento
4.
Medicine (Baltimore) ; 98(40): e17375, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577741

RESUMO

Achieving abstinence in schizophrenic smokers using a combination of medications and cognitive behavioral therapy is feasible; however, abstinence rates are significantly lower compared to the general population and studies are scanty. Additionally, maintaining sustained abstinence and preventing relapse is a major limiting factor and represents key tasks in managing tobacco dependence in schizophrenic patients. Several theories have been postulated to explain the higher tendency of tobacco use among schizophrenic individuals. Schizophrenic patients may use nicotine as a "self-medication" strategy to improve negative symptoms of schizophrenia. However, studies suggest that although nicotine may act as an anxiolytic acutely, chronic use of nicotine may lead to increased anxiety with the possibility of increased catecholamines, which is confirmed with the prevalence of tachycardia and hypertension in smokers in general. On this basis, the main objective of our present study was to assess anxiety in schizophrenic smoking and nonsmoking patients by comparing the number of anxiety and agitation episodes and evaluating the amount of antianxiety/antiagitation medication used by each group. A separate objective was to document the unmet needs of smoking cessation programs in treating schizophrenic patients. Consequently, in the present retrospective cohort study, it was observed that schizophrenic smokers tend to have higher anxiety episodes and utilize as-needed medications at a higher frequency compared to nonsmokers for the relief of anxiety and agitation symptoms. Further research is warranted to examine these results on a larger scale.


Assuntos
Ansiedade/epidemiologia , Fumar Cigarros/epidemiologia , Esquizofrenia/epidemiologia , Ansiolíticos/uso terapêutico , Antipsicóticos/uso terapêutico , Ansiedade/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológico , Fumantes , Abandono do Hábito de Fumar/métodos
5.
Medicine (Baltimore) ; 98(38): e17237, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567988

RESUMO

INTRODUCTION: With the second-generation antipsychotics (SGAs) widely applied to treat patients with schizophrenia, adverse effects, especially the metabolic syndrome (MetS), were paid more attention following by the efficacy of SGAs. Several studies have suggested that acupuncture could be an effective and safe intervention for MetS. Here, we present a study protocol to investigate the effect of electroacupuncture on MetS due to olanzapine and risperidone. METHODS: This study is a prospective, randomized, single-centered, patient-assessor-blinded, parallel-controlled clinical pilot trial. In all, 36 patients will be randomized to an experimental group or control group by a 1:1 ratio. All patients will receive lifestyle interventions. The experimental group will receive electroacupuncture treatment. The control group will receive sham electroacupuncture treatment. The primary outcomes are body mass index (BMI) and waist circumference (WC). The secondary outcome measures include blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), leptin, and adiponectin. We will assess at baseline, 8 weeks after intervention and at the end of 3 months' follow-up. DISCUSSION: The results of this trial are expected to provide data on the efficacy and safety of electroacupuncture on MetS due to olanzapine and risperidone, and potential biochemical mechanism.


Assuntos
Antipsicóticos/efeitos adversos , Eletroacupuntura , Síndrome Metabólica/terapia , Olanzapina/efeitos adversos , Risperidona/efeitos adversos , Antipsicóticos/uso terapêutico , Protocolos Clínicos , Eletroacupuntura/efeitos adversos , Eletroacupuntura/métodos , Humanos , Síndrome Metabólica/induzido quimicamente , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
6.
Neuropsychopharmacol Hung ; 21(3): 103-118, 2019 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-31537751

RESUMO

Dopamine D2 receptor partial agonists represent a new generation of atypical antipsychotics. Cariprazine, which has received centralized market authorization from the European Medicines Agency in 2017 for the treatment of adult patients with schizophrenia (including those with predominant negative symptoms of schizophrenia) differs from the other two partial agonist antipsychotics aripiprazole and brexpiprazole due to its unique features. Cariprazine is a dopamine D3 preferring D3/D2 partial agonist with very similar dopamine receptor subtype selectivity as dopamine. It has proven efficacy in the treatment of positive and negative symptoms of schizophrenia, as well as for relapse prevention. Further phase-3 clinical studies proved the efficacy of cariprazine in the acute treatment of manic or mixed episodes associated with bipolar I disorder, as well as in bipolar depression. For the adjunctive treatment of major depressive disorder, phase 3 studies are in progress.


Assuntos
Piperazinas/líquido cefalorraquidiano , Esquizofrenia , Antipsicóticos , Transtorno Depressivo Maior , Agonistas de Dopamina , Humanos , Receptores de Dopamina D3 , Esquizofrenia/tratamento farmacológico
7.
Niger J Clin Pract ; 22(9): 1281-1285, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489867

RESUMO

Background: The Medication Adherence Rating Scale (MARS) is a 10-item self-report measure of medication adherence in psychosis which is a vital predictor of illness course and outcome in patient with schizophrenia. The initial and subsequent studies have shown that MARS has good reliability and validity scores after correction for the small sample size in the index study. Aim: This study aimed to determine the psychometric properties of MARS among outpatients with schizophrenia at the outpatient clinic of the Neuropsychiatric Hospital Aro Abeokuta Ogun State Nigeria. Methods: Intra-class correlation coefficient (ICC) was used to determine the internal consistency, item-total correlations, and reliability of the instrument. Factor analysis was done using principal component analysis with varimax rotation. Results: The intra-class correlation coefficient (ICC) for these 10 items (at time T1) was 0.6 with a P value of <0.001 while for the test--retest analysis was 0.7 with a P value of 0.04. A principal components factor analysis with varimax rotation produced a four-factor solution and factor 4 was found to be the most internally consistent, with Cronbach's alpha of 0.63. Conclusion: This study supports the internal consistency, test--retest reliability, and constructs validity of the MARS.


Assuntos
Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Psicometria/instrumentação , Esquizofrenia/tratamento farmacológico , Inquéritos e Questionários/normas , Adulto , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Pacientes Ambulatoriais , Transtornos Psicóticos , Reprodutibilidade dos Testes , Esquizofrenia/diagnóstico , Autorrelato
8.
Psychiatr Danub ; 31(Suppl 3): 543-548, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488788

RESUMO

BACKGROUND: The attitudes of schizophrenic patients toward medications directly impact the treatment compliance. Although noncompliance represents a serious concern in long-term schizophrenia treatment, a detailed information on the factors that impair compliance is still limited. The present study aims to assess the factors related to noncompliance with antipsychotics agents, in long-term treated chronic paranoid schizophrenia patients. SUBJECTS AND METHODS: Two groups of such patients (total number n=162) were analyzed and compared: 1). patients with symptomatic remission on haloperidol (n=32), clozapine (n=40) or olanzapine (n=45), and 2). drug resistant patients (n=45). The mean duration of the disease was 19.3 years. RESULTS: Altogether, in our patient sample, a better drug attitude was found in the olanzapine and clozapine groups. Our findings have also revealed that worse attitude toward antipsychotics correlated with an earlier onset of schizophrenia, younger patient age, shorter duration of the disease, higher burden of symptoms, treatment with a typical antipsychotics, and higher severity of akathisia. CONCLUSION: Our results suggest that detecting factors that influence the patient's attitude toward medications might be helpful for designing targeted educational strategies in chronic schizophrenia patients (particularly those with the high risk of noncompliance), and further trials are warranted to explore this topic.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Cooperação do Paciente , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Clozapina/administração & dosagem , Clozapina/uso terapêutico , Haloperidol/administração & dosagem , Haloperidol/uso terapêutico , Humanos , Olanzapina/administração & dosagem , Olanzapina/uso terapêutico , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Fatores de Risco
9.
Psychiatr Danub ; 31(Suppl 3): 608-612, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488799

RESUMO

Schizophrenic patients have traditionally suffered from high rates of cardiovascular disease and early mortality. NICE guidelines suggest that several physical health measures be monitored regularly in these patients, and particularly those on antipsychotic medication, which has a wide side-effect profile that may potentiate the risk of cardiovascular disease and other comorbidities. This general practice audit aimed to determine the rates of physical health monitoring in primary care in patients on antipsychotic medication for over a year for psychotic symptoms or schizophrenia. The search was conducted in three different general practices in March 2019, yielding 19, 8 and 30 patients respectively, with a total of 57 patients. This audit aims to record and analyse rates of monitoring of a range of physical health measures recommended by NICE guidelines over the past year. The results demonstrated that physical health monitoring was poor amongst all the practices audited, especially that of prolactin and waist circumference. We recommend that these rates of monitoring be improved, through implementing templates or the delivery of targeted education to general practitioners and nurses.


Assuntos
Antipsicóticos/efeitos adversos , Medicina Geral , Atenção Primária à Saúde , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Auditoria Clínica , Humanos , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia
10.
Cochrane Database Syst Rev ; 8: CD006570, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31425609

RESUMO

BACKGROUND: Catatonia is a debilitating disorder of movement and volition associated with schizophrenia and some other mental illnesses. People with catatonia are more likely to require hospitalisation and highly supervised care than those without the disorder. They also have an increased risk of secondary complications such as pneumonia, malnutrition and dehydration. The mainstay of treatment has been drug therapies and electroconvulsive therapy. OBJECTIVES: To compare the effects of benzodiazepines with other drugs, placebo or electroconvulsive therapy for catatonia in people with schizophrenia or other similar serious mental illnesses (SMIs). SEARCH METHODS: We updated our previous search (28 February 2007) by searching the Cochrane Schizophrenia Group's Study-Based Register of Trials (9 November 2016; 6 February 2019). This register is compiled by systematic searches of major resources (including CENTRAL, MEDLINE, Embase, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. We also manually searched reference lists from studies selected by the search. SELECTION CRITERIA: All controlled clinical trials that randomised people who have schizophrenia or other similar SMI and experiencing catatonia to receive benzodiazepines or another relevant treatment. We included studies that met our inclusion criteria and reported usable data. We excluded those not meeting our inclusion criteria or those not reporting usable data. We contacted authors when we required further information; and if we received no response, we put those studies aside as 'awaiting assessment'. DATA COLLECTION AND ANALYSIS: Review authors extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis using a fixed-effect model. We completed a 'Risk of bias' assessment for the included study and generated a 'Summary of findings' table using GRADE. MAIN RESULTS: The searches found 130 citations, from which we could identify 22 possibly relevant studies. From these, we could only include one study. This study had a relatively small sample size of 17 participants who received lorazepam or oxazepam and were drug free for one week before the trial started. The only usable data reported by this study were clinically important change in symptoms of catatonia measured as 50% improvement on the Visual Analogue Scale (VAS). There was no difference in the numbers of participants showing a clinically important change in their catatonic symptoms (RR 0.95, 95% CI 0.42 to 2.16; participants = 17; studies = 1; very low quality evidence).No data were reported for other important outcomes of hospital stay, clinically important change in satisfaction with care, global state, adverse effects or general functioningWe did find a few studies meeting our inclusion criteria but they reported no usable data. We had to exclude these. Although poorly reported, these studies do illustrate that relevant studies have been undertaken - they are not impossible to design and conduct. AUTHORS' CONCLUSIONS: Analysis of the results from this review, which was a head-to-head comparison of two benzodiazepine monotherapies, does not show a clear difference in effect. No data were available for benzodiazepines compared to placebo or standard care. The lack of usable data and very low quality of data available makes it impossible to draw firm conclusions and further studies with a high-quality methodology and reporting are required in order to determine more definitively the outcomes associated with benzodiazepine use in the clinical management of catatonia in persons with schizophrenia and other SMI.


Assuntos
Benzodiazepinas/uso terapêutico , Catatonia/tratamento farmacológico , Esquizofrenia Catatônica/tratamento farmacológico , Antipsicóticos/uso terapêutico , Eletroconvulsoterapia , Humanos , Transtornos Mentais/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico
11.
Cochrane Database Syst Rev ; 8: CD012116, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31425623

RESUMO

BACKGROUND: Schizophrenia is a serious chronic mental illness affecting an estimated 21 million people worldwide and there is increasing evidence linking inflammation in the brain to the pathophysiology of schizophrenia. Antipsychotic drugs are the conventional treatment for people with schizophrenia but are not always fully effective. Acetylsalicylic acid (aspirin) is a non-steroidal anti-inflammatory drug (NSAID) with properties that inhibit the proinflammatory status of the brain. Using aspirin as an adjunct (add-on) treatment to antipsychotics or as a stand-alone treatment could be a novel, relatively inexpensive option for people with schizophrenia. OBJECTIVES: To review the effects of acetylsalicylic acid (aspirin) as adjunct (add-on) or as stand-alone treatment for people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (last search 8 March 2018) which is based on regular searches of MEDLINE, Embase, PubMed, CINAHL, BIOSIS, AMED, PsycINFO and registries of Clinical Trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: Randomised clinical trials focusing on aspirin for people with schizophrenia. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat (ITT) basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: We included two studies, both comparing the effects of adding aspirin to standard antipsychotic treatment with adding placebo to standard antipsychotic treatment. We were hoping to find high-quality data for seven main outcomes of importance: clinically important change in global state, mental state, cognitive functioning and quality of life, numbers leaving the study early, incidence of gastrointestinal adverse events and hospital admission. Clinically important change data were not reported. Global state data were reported by one study as 'unspecified problem necessitating change in dose or type of antipsychotics'; there was no clear difference between treatment groups for this outcome (RR 0.75, 95% CI 0.30 to 1.88; studies = 1; participants = 70; very low-quality evidence). Both trials measured mental state using the Positive and Negative Symptom Scale (PANSS), and mean total PANSS endpoint scores favoured the adjunct aspirin group in the medium term (MD -6.56, 95% CI -12.04 to -1.08; studies = 2; participants = 130; very low-quality evidence). Less than 10% of each group's participants left the studies early (for any reason) and by around three months there was no clear difference between numbers leaving early from the aspirin group compared to numbers leaving early from the placebo group suggesting aspirin is acceptable (RR 1.12, 95% CI 0.40 to 3.14; studies = 2; participants = 130; very low-quality evidence). There was some gastric upset in both groups but rates were not clearly different between the treatment groups (RR 1.03, 95% CI 0.55 to 1.94; studies = 1; participants = 70; very low-quality evidence). We are unclear if 'change in hospital status' is an unfavourable outcome or not as one study reported equivocal data (RR 0.56, 95% CI 0.05 to 5.90; studies = 1; participants = 70; very low-quality evidence). It should be noted that all the above results were based on data of very low-quality and were difficult to interpret for clinicians or patients, and that the two studies, completed in the last decade, failed to report any usable outcomes on cognitive functioning or quality of life. AUTHORS' CONCLUSIONS: We highlighted the evidence that some pioneering researchers feel this question is important enough to merit testing in randomised trials. However, we also highlighted that the evidence produced from these trials was weak and inconclusive. It was impossible to draw clear conclusions on the therapeutic value of aspirin for schizophrenia from these short, small and limited trials.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Quimioterapia Adjuvante , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Artigo em Russo | MEDLINE | ID: mdl-31464292

RESUMO

AIM: To conduct a comprehensive pharmacoeconomic evaluation of feasibility of treatment with cariprazine (reagila) in patients with schizophrenia. MATERIAL AND METHODS: A retrospective study using the pharmacoeconomic cost analysis, budget impact analysis, and cost-effectiveness analysis was performed. Data on cariprazine were compared to those on sertindole. RESULTS: If cariprazine is used instead of sertindole, the cost saved will amount to 30.8% per patient per year. If sertindole is fully replaced with cariprazine, the costs related to treatment of patients with a second generation antipsychotics funded by the state will be reduced by 97.8 million rubles over 3 years (30.9%). Gradual replacement of sertindole with cariprazine will make it possible to reduce budget expenditures by 20.1% or 63.8 million rubles over 3 years. This replacement will make it possible to provide therapy to additional 44.6% of patients, or 561 people. In this case, the number of patients receiving therapy will increase from 1257 to 1818. CONCLUSION: The results of the pharmacoeconomic analysis show that the registration of cariprazine (reagila) in the Russian Federation as therapeutic drug is economically feasible.


Assuntos
Antipsicóticos , Piperazinas , Esquizofrenia , Antipsicóticos/economia , Antipsicóticos/uso terapêutico , Humanos , Piperazinas/economia , Piperazinas/uso terapêutico , Estudos Retrospectivos , Federação Russa , Esquizofrenia/tratamento farmacológico
13.
Harefuah ; 158(7): 449-452, 2019 Jul.
Artigo em Hebraico | MEDLINE | ID: mdl-31339244

RESUMO

BACKGROUND: About a third of schizophrenia patients would not have sufficient clinical response to antipsychotic treatment. The only drug approved for this population is clozapine, yet worldwide reports suggest underuse of clozapine and significant delay in initiating treatment. OBJECTIVES: To assess, for the first time in Israel, the rate of clozapine use in patients with schizophrenia. METHODS: A retrospective cohort study of "Clalit Health Services" electronic records was conducted. People diagnosed with schizophrenia (F.20 ICD 10 code) who had at least one prescription filled for clozapine were followed up between 2012 and 2014. RESULTS: Of 28,983 people diagnosed with schizophrenia, clozapine was prescribed and purchased by 1817 (6.5%) patients during the study period. In addition, 60% of patients with clozapine had polytherapy with other antipsychotic compound or lithium. Polytherapy was associated with HR of 2.1 for morality during the follow-up period. CONCLUSIONS: Clozapine is underutilized in Israel, similar to reports from other countries. Moreover, the data suggests that when treatment is given it is not optimized, as reflected by high rates of polytherapy associated with increased mortality. Using therapeutic drug monitoring, now available in Israel, for clozapine might increase clozapine dosage optimization.


Assuntos
Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Humanos , Israel , Estudos Retrospectivos
14.
Harefuah ; 158(7): 453-457, 2019 Jul.
Artigo em Hebraico | MEDLINE | ID: mdl-31339245

RESUMO

INTRODUCTION: Long-acting injectable antipsychotics (LAI AP) were mainly developed with the intention to improve adherence to treatment in schizophrenia patients and to reduce the high rates of relapses and re-hospitalizations due to treatment discontinuation. Several studies comparing LAI AP with oral antipsychotics in schizophrenia have been performed, in which RCTs (considered to be the 'gold standard' for clinical trial design) generally show no benefit for LAI AP over oral drugs, whereas observational studies do. The more pragmatic the study design, the more likely it is to show a benefit for LAI AP versus oral therapy. Seeing that the percentage of patients who are currently being treated with LAI AP is far from the percentage of non-adherent patients, it can be argued that LAI AP are significantly underused. LAI AP formulations of antipsychotics have traditionally been used for those patients with schizophrenia with the most severe symptoms, poorest compliance, most hospitalizations, and poorest outcomes, namely at the latter stages of their illness. However, an increasing number of authors suggest that early-phase patients may have the most to gain from LAI AP, at a time when their disorder is most treatable and when avoidance of recurrences and re-hospitalizations may lead to the greatest benefits. To prove the advantage of LAI AP versus oral antipsychotics, there has been an evolution to a new type of clinical trial design that combines some of the best features of both naturalistic "real life" studies and RCTs, namely pragmatic RCT. Currently, there is an ongoing trial in Israel and European countries (the EULAST study) that is an example of this kind of "new" clinical trial design. EULAST is a pragmatic randomized open label cohort study that includes a naturalistic type of follow-up among schizophrenic patients who are early in the disease course. Hopefully, it will dispel doubts concerning the advantages of LAI AP versus oral antipsychotics and will help clinicians to optimize patient's outcomes.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Estudos de Coortes , Preparações de Ação Retardada , Europa (Continente) , Humanos , Israel
15.
Psychiatr Danub ; 31(2): 157-161, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31291219

RESUMO

Schizophrenia and bipolar disorders are serious psychiatric disorders with substantial health risks. Asenapine is a new second-generation antipsychotic, available as a sublingual tablet, approved in Europe for the treatment of moderate-to-severe manic episodes in adults, and in US for manic or mixed episodes of bipolar I disorder in adults and adolescents. In this review, we searched the available literature to appreciate the role of asenapine in the management of psychiatric conditions such as bipolar disorders and schizophrenia and describe its mechanism of action, efficacy and tolerability. Asenapine has demonstrated efficacy in the management of bipolar disorders and schizophrenia, while a possible role in the management of borderline personality disorder and agitation needs further research. Asenapine has favourable side effects profile and combining with other pharmacological treatment in post-traumatic stress disorder has shown promising results. Asenapine fulfils important requirements of efficacy and tolerability as an anti-psychotic. These findings should support psychiatrists and pharmacists in the care of their patients while on asenapine.


Assuntos
Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Transtorno da Personalidade Borderline/tratamento farmacológico , Europa (Continente) , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Estados Unidos
16.
Acta Med Hist Adriat ; 17(1): 91-102, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31315410

RESUMO

In the first half of the 20th century, in most European countries, it was thought that cholinesterase and other drugs that counteract acetylcholine should reduce the manifestations of schizophrenia. In 1937, Fiamberti (1894-1970) introduced the transorbital method of lobotomy which established the use of acetylcholine shock treatment for curing the disturbances of schizophrenia. Accepting the idea that the psychic alterations of schizophrenia were caused by a pathological interruption of nerve conduction at a presumably cortical level, Fiamberti thought he could apply this to the clinical field using the properties of acetylcholine, an acetic ester of choline. Here, we examined, in detail, the contribution of Mario Fiamberti to acetylcholine therapy.


Assuntos
Acetilcolina/história , Hospitais Psiquiátricos/história , Esquizofrenia/história , Acetilcolina/uso terapêutico , História do Século XX , Humanos , Psicocirurgia/história , Esquizofrenia/tratamento farmacológico
17.
Curr Med Chem ; 26(25): 4885-4913, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291870

RESUMO

Schizophrenia is a chronic psychiatric disorder that affects about 1 in 100 people around the world and results in persistent emotional and cognitive impairments. Untreated schizophrenia leads to deterioration in quality of life and premature death. Although the clinical efficacy of dopamine D2 receptor antagonists against positive symptoms of schizophrenia supports the dopamine hypothesis of the disease, the resistance of negative and cognitive symptoms to these drugs implicates other systems in its pathophysiology. Many studies suggest that abnormalities in glutamate homeostasis may contribute to all three groups of schizophrenia symptoms. Scientific considerations also include disorders of gamma-aminobutyric acid-ergic and serotonergic neurotransmissions as well as the role of the immune system. The purpose of this review is to update the most recent reports on the discovery and development of non-dopaminergic agents that may reduce positive, negative, and cognitive symptoms of schizophrenia, and may be alternative to currently used antipsychotics. This review collects the chemical structures of representative compounds targeting metabotropic glutamate receptor, gamma-aminobutyric acid type A receptor, alpha 7 nicotinic acetylcholine receptor, glycine transporter type 1 and glycogen synthase kinase 3 as well as results of in vitro and in vivo studies indicating their efficacy in schizophrenia. Results of clinical trials assessing the safety and efficacy of the tested compounds have also been presented. Finally, attention has been paid to multifunctional ligands with serotonin receptor affinity or phosphodiesterase inhibitory activity as novel strategies in the search for dedicated medicines for patients with schizophrenia.


Assuntos
Antipsicóticos/uso terapêutico , Descoberta de Drogas , Esquizofrenia/tratamento farmacológico , Animais , Antipsicóticos/síntese química , Antipsicóticos/química , Humanos , Estrutura Molecular
18.
BMC Neurol ; 19(1): 174, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31325958

RESUMO

BACKGROUND: Tardive dyskinesia (TD) is a serious, often irreversible movement disorder caused by prolonged exposure to antipsychotics; identifying patients at risk for TD is critical to preventing it. Predictive models for the occurrence of TD can improve patient monitoring and inform implementation of counteractive interventions. This study aims to identify risk factors associated with TD and to develop a model using a retrospective data analysis to predict the incidence of TD among patients taking antipsychotic medications. METHODS: Adult patients with schizophrenia, major depressive disorder, or bipolar disorder taking oral antipsychotics were identified in a Medicaid claims database (covering six US states from 1997 to 2016) and divided into cohorts based on whether they developed TD within 1 year after the first observed claim for antipsychotics. Patient characteristics between cohorts were compared, and univariate Cox analyses were used to identify potential TD risk factors. A cross-validated version of the least absolute shrinkage and selection operator regression method was used to develop a parsimonious multivariable Cox proportional hazards model to predict diagnosis of TD. RESULTS: A total of 189,415 eligible patients were identified. Potential TD risk factors were identified based on the cohort analysis within a sample of 151,280 patients with at least 1 year of continuous eligibility. The prediction model had a clinically meaningful concordance of 70% and was well calibrated (P = 0.32 for Hosmer-Lemeshow goodness-of-fit test). Age (hazard ratio [HR] = 1.04, P < 0.001), diagnosis of schizophrenia (HR = 1.99, P < 0.001), antipsychotic dosage (up to 100 mg/day chlorpromazine equivalent; HR = 1.65, P < 0.01), and comorbid bipolar and related disorders (HR = 1.39, P < 0.01) were significantly associated with an increased risk of TD. Other potential risk factors included history of extrapyramidal symptoms (HR = 1.35), other movement disorders (parkinsonism, HR = 1.43; bradykinesia, HR = 1.44; tremors, HR = 2.12, and myoclonus, HR = 2.33), and diabetes (HR = 1.13). A modest reduction in the risk of TD was associated with the use of second-generation antipsychotics (HR = 0.85) versus first-generation drugs. CONCLUSIONS: This study identified factors associated with development of TD among patients taking antipsychotics. The prediction model described herein can enable physicians to better monitor patients at high risk for TD and recommend appropriate treatment plans to help maintain quality of life.


Assuntos
Antipsicóticos/efeitos adversos , Discinesia Tardia/induzido quimicamente , Adulto , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Esquizofrenia/tratamento farmacológico
19.
Lancet ; 394(10202): 939-951, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31303314

RESUMO

BACKGROUND: Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials. METHODS: We did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919. FINDINGS: We identified 54 417 citations and included 402 studies with data for 53 463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from -0·89 (95% CrI -1·08 to -0·71) for clozapine to -0·03 (-0·59 to 0·52) for levomepromazine (40 815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31 179 participants) varied from -0·69 (95% CrI -0·86 to -0·52) for amisulpride to -0·17 (-0·31 to -0·04) for brexpiprazole, for negative symptoms (32 015 participants) from -0·62 (-0·84 to -0·39; clozapine) to -0·10 (-0·45 to 0·25; flupentixol), for depressive symptoms (19 683 participants) from -0·90 (-1·36 to -0·44; sulpiride) to 0·04 (-0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause discontinuation (42 672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30 770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24 911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide). Mean differences compared to placebo for weight gain (28 317 participants) ranged from -0·16 kg (-0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21 569 participants) from -77·05 ng/mL (-120·23 to -33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15 467 participants) from -2·21 ms (-4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole). Conclusions for the primary outcome did not substantially change after adjusting for possible effect moderators or in sensitivity analyses (eg, when excluding placebo-controlled studies). The confidence in evidence was often low or very low. INTERPRETATION: There are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences. FUNDING: German Ministry of Education and Research and National Institute for Health Research.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Administração Oral , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Pesquisa Comparativa da Efetividade/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(6): 701-705, 2019 Jun 28.
Artigo em Chinês | MEDLINE | ID: mdl-31304933

RESUMO

The negative symptoms and cognitive symptoms of schizophrenia patients are still clinical problems to be solved. Schizophrenia patients are abnormal in oxidative stress, immune regulation, and anti-histone deacetylase (HDAC), while sulforaphane plays a role in anti-oxidative stress, anti-inflammation, and anti-HDAC. Therefore, the sulforaphane could improve the negative symptoms and cognitive deficits of schizophrenia.


Assuntos
Isotiocianatos/uso terapêutico , Esquizofrenia , Cognição , Humanos , Esquizofrenia/tratamento farmacológico
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