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[PMID]:28791693
[Au] Autor:Loy JH; Merry SN; Hetrick SE; Stasiak K
[Ad] Endereço:Child and Adolescent Mental Health, Waikato DHB, 206 Colllingwood Street, Hamilton, New Zealand.
[Ti] Título:Atypical antipsychotics for disruptive behaviour disorders in children and youths.
[So] Source:Cochrane Database Syst Rev;8:CD008559, 2017 08 09.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: This is an update of the original Cochrane Review, last published in 2012 (Loy 2012). Children and youths with disruptive behaviour disorders may present to health services, where they may be treated with atypical antipsychotics. There is increasing usage of atypical antipsychotics in the treatment of disruptive behaviour disorders. OBJECTIVES: To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths. The aim was to evaluate each drug separately rather than the class effect, on the grounds that each atypical antipsychotic has different pharmacologic binding profile (Stahl 2013) and that this is clinically more useful. SEARCH METHODS: In January 2017, we searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers. SELECTION CRITERIA: Randomised controlled trials of atypical antipsychotics versus placebo in children and youths aged up to and including 18 years, with a diagnosis of disruptive behaviour disorders, including comorbid ADHD. The primary outcomes were aggression, conduct problems and adverse events (i.e. weight gain/changes and metabolic parameters). The secondary outcomes were general functioning, noncompliance, other adverse events, social functioning, family functioning, parent satisfaction and school functioning. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors (JL and KS) independently collected, evaluated and extracted data. We used the GRADE approach to assess the quality of the evidence. We performed meta-analyses for each of our primary outcomes, except for metabolic parameters, due to inadequate outcome data. MAIN RESULTS: We included 10 trials (spanning 2000 to 2014), involving a total of 896 children and youths aged five to 18 years. Bar two trials, all came from an outpatient setting. Eight trials assessed risperidone, one assessed quetiapine and one assessed ziprasidone. Nine trials assessed acute efficacy (over four to 10 weeks); one of which combined treatment with stimulant medication and parent training. One trial was a six-month maintenance trial assessing symptom recurrence.The quality of the evidence ranged from low to moderate. Nine studies had some degree of pharmaceutical support/funding. Primary outcomesUsing the mean difference (MD), we combined data from three studies (238 participants) in a meta-analysis of aggression, as assessed using the Aberrant Behaviour Checklist (ABC) ‒ Irritability subscale. We found that youths treated with risperidone show reduced aggression compared to youths treated with placebo (MD -6.49, 95% confidence interval (CI) -8.79 to -4.19; low-quality evidence). Using the standardised mean difference (SMD), we pooled data from two risperidone trials (190 participants), which used different scales: the Overt Aggression Scale ‒ Modified (OAS-M) Scale and the Antisocial Behaviour Scale (ABS); as the ABS had two subscales that could not be combined (reactive and proactive aggression), we performed two separate analyses. When we combined the ABS Reactive subscale and the OAS-M, the SMD was -1.30 in favour of risperidone (95% CI -2.21 to -0.40, moderate-quality evidence). When we combined the ABS Proactive subscale and OAS-M, the SMD was -1.12 (95% CI -2.30 to 0.06, moderate-quality evidence), suggesting uncertainty about the estimate of effect, as the confidence intervals overlapped the null value. In summary, there was some evidence that aggression could be reduced by risperidone. Data were lacking on other atypical antipsychotics, like quetiapine and ziprasidone, with regard to their effects on aggression.We pooled data from two risperidone trials (225 participants) in a meta-analysis of conduct problems, as assessed using the Nisonger Child Behaviour Rating Form ‒ Conduct Problem subscale (NCBRF-CP). This yielded a final mean score that was 8.61 points lower in the risperidone group compared to the placebo group (95% CI -11.49 to -5.74; moderate-quality evidence).We investigated the effect on weight by performing two meta-analyses. We wanted to distinguish between the effects of antipsychotic medication only and the combined effect with stimulants, since the latter can have a counteracting effect on weight gain due to appetite suppression. Pooling two trials with risperidone only (138 participants), we found that participants on risperidone gained 2.37 kilograms (kg) more (95% CI 0.26 to 4.49; moderate-quality evidence) than those on placebo. When we added a trial where all participants received a combination of risperidone and stimulants, we found that those on the combined treatment gained 2.14 kg more (95% CI 1.04 to 3.23; 3 studies; 305 participants; low-quality evidence) than those on placebo. Secondary outcomesOut of the 10 included trials, three examined general functioning, social functioning and parent satisfaction. No trials examined family or school functioning. Data on non-compliance/attrition rate and other adverse events were available from all 10 trials. AUTHORS' CONCLUSIONS: There is some evidence that in the short term risperidone may reduce aggression and conduct problems in children and youths with disruptive behaviour disorders There is also evidence that this intervention is associated with significant weight gain.For aggression, the difference in scores of 6.49 points on the ABC ‒ Irritability subscale (range 0 to 45) may be clinically significant. It is challenging to interpret the clinical significance of the differential findings on two different ABS subscales as it may be difficult to distinguish between reactive and proactive aggression in clinical practice. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant. Weight gain remains a concern.Caution is required in interpreting the results due to the limitations of current evidence and the small number of high-quality trials. There is a lack of evidence to support the use of quetiapine, ziprasidone or any other atypical antipsychotic for disruptive behaviour disorders in children and youths and no evidence for children under five years of age. It is uncertain to what degree the efficacy found in clinical trials will translate into real-life clinical practice. Given the effectiveness of parent-training interventions in the management of these disorders, and the somewhat equivocal evidence on the efficacy of medication, it is important not to use medication alone. This is consistent with current clinical guidelines.
[Mh] Termos MeSH primário: Agressão/efeitos dos fármacos
Antipsicóticos/uso terapêutico
Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico
Dibenzotiazepinas/uso terapêutico
Piperazinas/uso terapêutico
Fumarato de Quetiapina/uso terapêutico
Risperidona/uso terapêutico
Tiazóis/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Antipsicóticos/efeitos adversos
Transtornos de Ansiedade/tratamento farmacológico
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico
Criança
Pré-Escolar
Transtorno da Conduta/tratamento farmacológico
Transtorno Depressivo Maior/tratamento farmacológico
Dibenzotiazepinas/efeitos adversos
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
Risperidona/efeitos adversos
Ganho de Peso
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Dibenzothiazepines); 0 (Piperazines); 0 (Thiazoles); 2S3PL1B6UJ (Quetiapine Fumarate); 6UKA5VEJ6X (ziprasidone); L6UH7ZF8HC (Risperidone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD008559.pub3


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[PMID]:28387925
[Au] Autor:Mazhari S; Esmailian S; Shah-Esmaeili A; Goughari AS; Bazrafshan A; Zare M
[Ad] Endereço:Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
[Ti] Título:Chlorpromazine versus clotiapine for schizophrenia.
[So] Source:Cochrane Database Syst Rev;4:CD011810, 2017 Apr 07.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Schizophrenia is a chronic, disabling and severe mental disorder, characterised by disturbance in perception, thought, language, affect and motor behaviour. Chlorpromazine and clotiapine are among antipsychotic drugs used for the treatment of people with schizophrenia. OBJECTIVES: To determine the clinical effects, safety and cost-effectiveness of chlorpromazine compared with clotiapine for adults with schizophrenia. SEARCH METHODS: We searched Cochrane Schizophrenia's Trials Register (last update search 16/01/2016), which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the Register. SELECTION CRITERIA: All randomised clinical trials focusing on chlorpromazine versus clotiapine for schizophrenia. We included trials meeting our selection criteria and reporting useable data. 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 basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: We have included four studies, published between 1974 and 2003, randomising 276 people with schizophrenia to receive either chlorpromazine or clotiapine. The studies were poor at concealing allocation of treatment and blinding of outcome assessment. Our main outcomes of interest were clinically important change in global and mental state, specific change in negative symptoms, incidence of movement disorder (dyskinesia), leaving the study early for any reason, and costs. All reported data were short-term (under six months' follow-up).The trials did not report data for the important outcomes of clinically important change in global or mental state, or cost of care. Improvement in mental state was reported using the Positive and Negative Syndrome Scale (PANSS). When chlorpromazine was compared with clotiapine the average improvement scores for mental state using the PANSS total was higher in the clotiapine group (1 RCT, N = 31, MD 11.50 95% CI 9.42 to 13.58, very low-quality evidence). The average change scores on the PANSS negative sub-scale were similar between treatment groups (1 RCT, N = 21, MD -0.97 95% CI -2.76 to 0.82, very low-quality evidence). There was no clear difference in incidence of dyskinesia (1 RCT, N = 68, RR 3.00 95% CI 0.13 to 71.15, very low-quality evidence). Similar numbers of participants left the study early from each treatment group (3 RCTs, N = 158, RR 0.68 95% CI 0.24 to 1.88, very low-quality evidence). AUTHORS' CONCLUSIONS: Clinically important changes in global and mental state were not reported. Only one trial reported the average change in overall mental state; results favour clotiapine but these limited data are very difficult to trust due to methodological limitations of the study. The comparative effectiveness of chlorpromazine compared to clotiapine on change in global state remains unanswered. Results in this review suggest chlorpromazine and clotiapine cause similar adverse effects, although again, the quality of evidence for this is poor, making firm conclusions difficult.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Clorpromazina/uso terapêutico
Dibenzotiazepinas/uso terapêutico
Esquizofrenia/tratamento farmacológico
[Mh] Termos MeSH secundário: Antipsicóticos/efeitos adversos
Clorpromazina/efeitos adversos
Dibenzotiazepinas/efeitos adversos
Discinesia Induzida por Medicamentos/epidemiologia
Seres Humanos
Análise de Intenção de Tratamento
Pacientes Desistentes do Tratamento/estatística & dados numéricos
Ensaios Clínicos Controlados Aleatórios como Assunto
Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Dibenzothiazepines); U42B7VYA4P (Chlorpromazine); Z05HCY0X1T (clothiapine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD011810.pub2


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[PMID]:28349512
[Au] Autor:Zare M; Bazrafshan A
[Ad] Endereço:Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
[Ti] Título:Chlorpromazine versus metiapine for schizophrenia.
[So] Source:Cochrane Database Syst Rev;3:CD011655, 2017 Mar 25.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Chlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine derivative, has been reported to have potent antipsychotic characteristics. However, no evidence currently exists on the effectiveness of chlorpromazine in treatment of people with schizophrenia compared to metiapine, a newer antipsychotic. OBJECTIVES: To compare the effect of chlorpromazine versus metiapine for the treatment of people with schizophrenia SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials in November 2015 and 2016. SELECTION CRITERIA: All randomised controlled trials (RCTs) focusing on chlorpromazine versus metiapine for adults with schizophrenia. We included trials meeting our selection criteria and reporting useable data. 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 basis. For continuous data, we estimated the mean difference between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. MAIN RESULTS: We included three studies randomising 161 people with schizophrenia. Data were available for only two of our seven prestated main outcomes. Clinically important improvement in global state was measured using the Clinical Global Impression (CGI). There was no clear difference between chlorpromazine and metiapine groups (2 RCTs, n = 120, RR 1.11, 95% CI 0.84 to 1.47, very low quality evidence) and numbers of participants with parkinsonism at eight weeks were similar (2 RCTs, n = 70, RR 0.97, 95% CI 0.46 to 2.03, very low quality evidence). There were no useable data available for the other key outcomes of clinically important improvement in mental state, readmission due to relapse, satisfaction with treatment, aggressive or violent behaviour, or cost of care. AUTHORS' CONCLUSIONS: Chlorpromazine has been the mainstay treatment for schizophrenia for decades, yet available evidence comparing this drug to metiapine fails to provide high-quality trial based data. However, the need to determine whether metiapine is more or less effective than chlorpromazine seems to be lacking in clinical relevance and future research on this comparison seems unlikely.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Clorpromazina/uso terapêutico
Dibenzotiazepinas/uso terapêutico
Esquizofrenia/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Antipsicóticos/efeitos adversos
Clorpromazina/efeitos adversos
Dibenzotiazepinas/efeitos adversos
Seres Humanos
Doença de Parkinson Secundária/induzido quimicamente
Ensaios Clínicos Controlados Aleatórios como Assunto
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Dibenzothiazepines); 775D6D91J8 (metiapine); U42B7VYA4P (Chlorpromazine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170720
[Lr] Data última revisão:
170720
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD011655.pub2


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[PMID]:28333365
[Au] Autor:Barber S; Olotu U; Corsi M; Cipriani A
[Ad] Endereço:Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
[Ti] Título:Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia.
[So] Source:Cochrane Database Syst Rev;3:CD006324, 2017 03 23.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Between 40% and 70% of people with treatment-resistant schizophrenia do not respond to clozapine, despite adequate blood levels. For these people, a number of treatment strategies have emerged, including the prescription of a second anti-psychotic drug in combination with clozapine. OBJECTIVES: To determine the clinical effects of various clozapine combination strategies with antipsychotic drugs in people with treatment-resistant schizophrenia both in terms of efficacy and tolerability. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (to 28 August 2015) and MEDLINE (November 2008). We checked the reference lists of all identified randomised controlled trials (RCT). For the first version of the review, we also contacted pharmaceutical companies to identify further trials. SELECTION CRITERIA: We included only RCTs recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and 95% confidence intervals (CI) on an intention-to-treat basis using a random-effects meta-analysis. For continuous data, we calculated mean differences (MD) and 95% CIs. We used GRADE to create 'Summary of findings' tables and assessed risk of bias for included studies. MAIN RESULTS: We identified two further studies with 169 participants that met our inclusion criteria. This review now includes five studies with 309 participants. The quality of evidence was low, and, due to the high degree of heterogeneity between studies, we were unable to undertake a formal meta-analysis to increase the statistical power.For this update, we specified seven main outcomes of interest: clinical response in mental state (clinically significant response, mean score/change in mental state), clinical response in global state (mean score/change in global state), weight gain, leaving the study early (acceptability of treatment), service utilisation outcomes (hospital days or admissions to hospital) and quality of life.We found some significant differences between clozapine combination strategies for global and mental state (clinically significant response and change), and there were data for leaving the study early and weight gain. We found no data for service utilisation and quality of life. Clozapine plus aripiprazole versus clozapine plus haloperidolThere was no long-term significant difference between aripiprazole and haloperidol combination strategies in change of mental state (1 RCT, n = 105, MD 0.90, 95% CI -4.38 to 6.18, low quality evidence). There were no adverse effect data for weight gain but there was a benefit of aripiprazole for adverse effects measured by the LUNSERS at 12 weeks (1 RCT, n = 105, MD -4.90, 95% CI -8.48 to -1.32) and 24 weeks (1 RCT, n = 105, MD -4.90, 95% CI -8.25 to -1.55), but not 52 weeks (1 RCT, n = 105, MD -4.80, 95% CI -9.79 to 0.19). Similar numbers of participants from each group left the study early (1 RCT, n = 106, RR 1.27, 95% CI 0.72 to 2.22, very low quality evidence). Clozapine plus amisulpride versus clozapine plus quetiapine One study showed a significant benefit of amisulpride over quetiapine in the short term, for both change in global state (Clinical Global Impression (CGI): 1 RCT, n = 50, MD -0.90, 95% CI -1.38 to -0.42, very low quality evidence) and mental state (Brief Psychiatric Rating Scale (BPRS): 1 RCT, n = 50, MD -4.00, 95% CI -5.86 to -2.14, low quality evidence). Similar numbers of participants from each group left the study early (1 RCT, n = 56, RR 0.20, 95% CI 0.02 to 1.60, very low quality evidence) Clozapine plus risperidone versus clozapine plus sulpirideThere was no difference between risperidone and sulpiride for clinically significant response, defined by the study as 20% to 50% reduction in Positive and Negative Syndrome Scale (PANSS) (1 RCT, n = 60, RR 0.82, 95% CI 0.40 to 1.68, very low quality evidence). There were similar equivocal results for weight gain (1 RCT, n = 60, RR 0.40, 95% CI 0.08 to 1.90, very low quality evidence) and mental state (PANSS total: 1 RCT, n = 60, MD -2.28, 95% CI -7.41 to 2.85, very low quality evidence). No-one left the study early. Clozapine plus risperidone versus clozapine plus ziprasidoneThere was no difference between risperidone and ziprasidone for clinically significant response (1 RCT, n = 24, RR 0.80, 95% CI 0.28 to 2.27, very low quality evidence), change in global state CGI-II score (1 RCT, n = 22, MD -0.30, 95% CI -0.82 to 0.22, very low quality evidence), change in PANSS total score (1 RCT, n = 16, MD 1.00, 95% CI -7.91 to 9.91, very low quality evidence) or leaving the study early (1 RCT, n = 24, RR 1.60, 95% CI 0.73 to 3.49, very low quality evidence). Clozapine plus ziprasidone versus clozapine plus quetiapineOne study found, in the medium term, a superior effect for ziprasidone combination compared with quetiapine combination for clinically significant response in mental state (> 50% reduction PANSS: 1 RCT, n = 63, RR 0.54, 95% CI 0.35 to 0.81, low quality evidence), global state (CGI - Severity score: 1 RCT, n = 60, MD -0.70, 95% CI -1.18 to -0.22, low quality evidence) and mental state (PANSS total score: 1 RCT, n = 60, MD -12.30, 95% CI -22.43 to -2.17, low quality evidence). There was no effect for leaving the study early (1 RCT, n = 63, RR 0.52, CI 0.05 to 5.41, very low quality evidence). AUTHORS' CONCLUSIONS: The reliability of results from this review is limited, evidence is of low or very low quality. Furthermore, due to the limited number of included studies, we were unable to undertake formal meta-analyses. As a consequence, any conclusions drawn from these findings are based on single, small-sized RCTs with high risk of type II error. Properly conducted and adequately powered RCTs are required. Future trialists should seek to measure patient-important outcomes such as quality of life, as well as clinical response and adverse effects.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Clozapina/uso terapêutico
Esquizofrenia/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Antipsicóticos/efeitos adversos
Aripiprazol/efeitos adversos
Aripiprazol/uso terapêutico
Clozapina/efeitos adversos
Dibenzotiazepinas/uso terapêutico
Resistência a Medicamentos
Quimioterapia Combinada
Feminino
Haloperidol/efeitos adversos
Haloperidol/uso terapêutico
Seres Humanos
Masculino
Piperazinas/uso terapêutico
Fumarato de Quetiapina
Ensaios Clínicos Controlados Aleatórios como Assunto
Risperidona/uso terapêutico
Sulpirida/efeitos adversos
Sulpirida/análogos & derivados
Sulpirida/uso terapêutico
Tiazóis/uso terapêutico
Ganho de Peso
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Dibenzothiazepines); 0 (Piperazines); 0 (Thiazoles); 2S3PL1B6UJ (Quetiapine Fumarate); 7MNE9M8287 (Sulpiride); 82VFR53I78 (Aripiprazole); AA0G3TW31W (sultopride); J60AR2IKIC (Clozapine); J6292F8L3D (Haloperidol); L6UH7ZF8HC (Risperidone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170720
[Lr] Data última revisão:
170720
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD006324.pub3


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[PMID]:28271741
[Au] Autor:Miranda AS; Moreira FA; Teixeira AL
[Ad] Endereço:a Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina , Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
[Ti] Título:The preclinical discovery and development of quetiapine for the treatment of mania and depression.
[So] Source:Expert Opin Drug Discov;12(5):525-535, 2017 May.
[Is] ISSN:1746-045X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood. Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system. Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP's anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Transtorno Bipolar/tratamento farmacológico
Fumarato de Quetiapina/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Antipsicóticos/metabolismo
Antipsicóticos/farmacologia
Transtorno Bipolar/fisiopatologia
Dibenzotiazepinas/metabolismo
Dibenzotiazepinas/farmacologia
Avaliação Pré-Clínica de Medicamentos
Seres Humanos
Qualidade de Vida
Fumarato de Quetiapina/metabolismo
Fumarato de Quetiapina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Dibenzothiazepines); 2S3PL1B6UJ (Quetiapine Fumarate); V3H1ZVV9S6 (norquetiapine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1080/17460441.2017.1304378


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[PMID]:27803466
[Au] Autor:Kim DW; Weon KY; Hong EP; Chung EK; Lee KT
[Ad] Endereço:Department of Pharmaceutical Engineering, Cheongju University.
[Ti] Título:Comparative Physicochemical and Pharmacokinetic Properties of Quetiapine and Its Active Metabolite Norquetiapine.
[So] Source:Chem Pharm Bull (Tokyo);64(11):1546-1554, 2016.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Quetiapine (QTP) is an atypical antipsychotic drug commonly used to treat several psychiatric disorders and is metabolized into the active metabolite norquetiapine (NQTP). This study was designed to evaluate and compare the physicochemical properties, metabolic stability, brain distribution, and pharmacokinetics of QTP and NQTP. Compared to QTP, NQTP had a higher pK , solubility, and rat liver microsomal stability, optimal log D and similar log P values. For pharmacokinetic evaluation, QTP and NQTP were administered orally and intravenously to rats at various doses. The plasma QTP and NQTP concentrations in rats were determined by a fully-validated liquid-chromatography tandem mass spectrometry (LC-MS/MS). Over the investigated dosing range, both QTP and NQTP showed linear pharmacokinetics. Following oral administration of the same dose, the area under the concentration-time curve (AUC ) and maximum serum concentration (C ) were larger after NQTP administration compared to QTP administration. In addition, NQTP had a greater absolute oral bioavailability compared to QTP (15.6% vs. 0.63%, respectively). The brain-to-plasma concentration ratio was greater after NQTP administration compared to the QTP and NQTP ratios after QTP administration. NQTP administration results in increased systemic exposure and brain distribution compared to QTP administration. Future studies are needed to evaluate the pharmacologic and toxicologic effects of increased NQTP exposures.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Dibenzotiazepinas/metabolismo
Dibenzotiazepinas/farmacocinética
Microssomos Hepáticos/metabolismo
Fumarato de Quetiapina/metabolismo
Fumarato de Quetiapina/farmacocinética
[Mh] Termos MeSH secundário: Administração Oral
Animais
Química Física
Dibenzotiazepinas/administração & dosagem
Estabilidade de Medicamentos
Concentração de Íons de Hidrogênio
Masculino
Microssomos Hepáticos/química
Fumarato de Quetiapina/administração & dosagem
Ratos
Ratos Sprague-Dawley
Solubilidade
Distribuição Tecidual
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dibenzothiazepines); 2S3PL1B6UJ (Quetiapine Fumarate); V3H1ZVV9S6 (norquetiapine)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161103
[St] Status:MEDLINE


  7 / 2353 MEDLINE  
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[PMID]:27567425
[Au] Autor:Lurie Y; Gopher A; Hoffmann Y; Bentur Y
[Ad] Endereço:Israel Poison Information Center, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
[Ti] Título:Pediatric clotiapine poisoning: clinical manifestations and toxicokinetics.
[So] Source:Am J Emerg Med;34(12):2469.e1-2469.e2, 2016 Dec.
[Is] ISSN:1532-8171
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Antipsicóticos/envenenamento
Dibenzotiazepinas/envenenamento
Overdose de Drogas/terapia
[Mh] Termos MeSH secundário: Antipsicóticos/sangue
Dibenzotiazepinas/sangue
Overdose de Drogas/sangue
Overdose de Drogas/complicações
Seres Humanos
Hipertensão/induzido quimicamente
Lactente
Masculino
Miose/induzido quimicamente
Estupor/induzido quimicamente
Toxicocinética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Dibenzothiazepines); Z05HCY0X1T (clothiapine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160828
[St] Status:MEDLINE


  8 / 2353 MEDLINE  
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[PMID]:27056066
[Au] Autor:Desmarais P; Massoud F; Filion J; Nguyen QD; Bajsarowicz P
[Ad] Endereço:Division of Geriatric Medicine, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montreal, Québec, Canada philippe.desmarais.1@umontreal.ca.
[Ti] Título:Quetiapine for Psychosis in Parkinson Disease and Neurodegenerative Parkinsonian Disorders: A Systematic Review.
[So] Source:J Geriatr Psychiatry Neurol;29(4):227-36, 2016 Jul.
[Is] ISSN:0891-9887
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We performed a systematic review of randomized controlled trials to assess the high-level evidence regarding the role of quetiapine in the treatment of psychosis in patients with neurodegenerative parkinsonian disorders. Studies were included in the qualitative review if they (1) enrolled participants with diagnosis of Parkinson disease, Lewy body dementia, or any other neurodegenerative parkinsonian disorders; (2) assessed the efficacy of quetiapine; and (3) evaluated psychotic and motor outcomes using validated tools. Of the 341 manuscripts identified, 7 studies fulfilled our inclusion criteria. The studies' risk of bias was considered low. A total of 241 participants enrolled in these trials. Heterogeneity was high due to inclusion criteria, user definitions, assessment tools, and study design. Although not causing any motor deterioration, quetiapine failed to significantly reduce psychotic symptoms compared to placebo when objectively assessed on the Brief Psychotic Rating Scale, the most frequently reported scale in these studies. High loss to follow-up and dropout rates as well as significant improvement in psychotic symptoms in the placebo groups may have affected measurements of possible positive medication effects.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Doença por Corpos de Lewy/complicações
Doença de Parkinson/complicações
Transtornos Psicóticos/tratamento farmacológico
Fumarato de Quetiapina/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Dibenzotiazepinas/uso terapêutico
Feminino
Seres Humanos
Doença por Corpos de Lewy/psicologia
Masculino
Meia-Idade
Doença de Parkinson/psicologia
Transtornos Psicóticos/etiologia
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Dibenzothiazepines); 2S3PL1B6UJ (Quetiapine Fumarate)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170529
[Lr] Data última revisão:
170529
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160409
[St] Status:MEDLINE
[do] DOI:10.1177/0891988716640378


  9 / 2353 MEDLINE  
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[PMID]:26655594
[Au] Autor:Daglas R; Cotton SM; Allott K; Yücel M; Macneil CA; Hasty MK; Murphy B; Pantelis C; Hallam KT; Henry LP; Conus P; Ratheesh A; Kader L; Wong MT; McGorry PD; Berk M
[Ad] Endereço:Orygen, The National Centre of Excellence in Youth Mental Health, Locked Bag 10 (35, Poplar Road), Parkville, 3052 Victoria, Australia; Centre for Youth Mental Health, University of Melbourne, 35 Poplar Road, Parkville, 3052 Victoria, Australia. Electronic address: rose.daglas@orygen.org.au.
[Ti] Título:A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study.
[So] Source:Eur Psychiatry;31:20-8, 2016 Jan.
[Is] ISSN:1778-3585
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. METHODS: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. RESULTS: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. CONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
[Mh] Termos MeSH primário: Antimaníacos/uso terapêutico
Antipsicóticos/uso terapêutico
Transtorno Bipolar/tratamento farmacológico
Transtorno Bipolar/psicologia
Cognição/efeitos dos fármacos
Compostos de Lítio/uso terapêutico
Fumarato de Quetiapina/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Dibenzotiazepinas/uso terapêutico
Feminino
Seguimentos
Seres Humanos
Inteligência
Masculino
Memória
Método Simples-Cego
Fatores de Tempo
Resultado do Tratamento
Aprendizagem Verbal
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimanic Agents); 0 (Antipsychotic Agents); 0 (Dibenzothiazepines); 0 (Lithium Compounds); 2S3PL1B6UJ (Quetiapine Fumarate)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160118
[Lr] Data última revisão:
160118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151215
[St] Status:MEDLINE


  10 / 2353 MEDLINE  
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[PMID]:26436896
[Au] Autor:Cross AJ; Widzowski D; Maciag C; Zacco A; Hudzik T; Liu J; Nyberg S; Wood MW
[Ad] Endereço:AstraZeneca Neuroscience Innovative Medicines, Cambridge, MA, USA.
[Ti] Título:Quetiapine and its metabolite norquetiapine: translation from in vitro pharmacology to in vivo efficacy in rodent models.
[So] Source:Br J Pharmacol;173(1):155-66, 2016 Jan.
[Is] ISSN:1476-5381
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct in vitro pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine. EXPERIMENTAL APPROACH: We evaluated quetiapine and norquetiapine, using in vitro binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions and compared these activities with a representative range of established antipsychotics and antidepressants. To determine how the in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to established antidepressant-like and anxiolytic-like drug action. KEY RESULTS: Norquetiapine had equivalent activity to established antidepressants at the noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In in vivo receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5-HT1A receptors, and the anxiolytic-like activity of norquetiapine in rat punished responding was blocked by the 5-HT1A antagonist, WAY100635. CONCLUSIONS AND IMPLICATIONS: Quetiapine and norquetiapine have multiple in vitro pharmacological actions, and results from preclinical studies suggest that activity at NET and 5-HT1A receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine.
[Mh] Termos MeSH primário: Ansiolíticos/farmacologia
Antidepressivos/farmacologia
Dibenzotiazepinas/farmacologia
Fumarato de Quetiapina/farmacologia
[Mh] Termos MeSH secundário: Animais
Condicionamento Operante/efeitos dos fármacos
Dibenzotiazepinas/antagonistas & inibidores
Modelos Animais de Doenças
Desamparo Aprendido
Seres Humanos
Resposta de Imobilidade Tônica/efeitos dos fármacos
Masculino
Camundongos
Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo
Piperazinas/farmacologia
Punição
Piridinas/farmacologia
Ensaio Radioligante
Ratos
Agonistas de Receptores 5-HT1 de Serotonina/farmacologia
Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Antidepressive Agents); 0 (Dibenzothiazepines); 0 (Norepinephrine Plasma Membrane Transport Proteins); 0 (Piperazines); 0 (Pyridines); 0 (Serotonin 5-HT1 Receptor Agonists); 0 (Serotonin 5-HT1 Receptor Antagonists); 2S3PL1B6UJ (Quetiapine Fumarate); 71IH826FEG (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide); V3H1ZVV9S6 (norquetiapine)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151006
[St] Status:MEDLINE
[do] DOI:10.1111/bph.13346



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