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[PMID]:28858444
[Au] Autor:Reeves S; Bertrand J; McLachlan E; D'Antonio F; Brownings S; Nair A; Greaves S; Smith A; Dunn JT; Marsden P; Kessler R; Uchida H; Taylor D; Howard R
[Ad] Endereço:Division of Psychiatry, University College London, 6th Floor, Maple House, 149 Tottenham Court Rd, London W1T 7NF. suzanne.reeves@ucl.ac.uk.
[Ti] Título:A Population Approach to Guide Amisulpride Dose Adjustments in Older Patients With Alzheimer's Disease.
[So] Source:J Clin Psychiatry;78(7):e844-e851, 2017 Jul.
[Is] ISSN:1555-2101
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We have previously reported high dopamine D2/3 receptor occupancies at low amisulpride concentrations in older people with Alzheimer's disease (AD), during off-label treatment of AD-related psychosis. This post hoc analysis explored pharmacokinetic (concentration) and pharmacodynamic (prolactin, D2/3 occupancy) contributions to symptom reduction and extrapyramidal side effects (EPS) to inform AD-specific dose adjustments. METHODS: Population pharmacokinetic-pharmacodynamic models were developed by combining pharmacokinetic data from a phase 1 study in 20 healthy older people with pharmacokinetic prolactin, [¹8F]fallypride D2/3 receptor imaging, and clinical outcome data from 28 older patients prescribed open amisulpride (25-75 mg/d) to treat AD-related psychosis. Model predictions were used to simulate dose-response and dose-EPS. RESULTS: Symptom reduction (delusions) was associated with amisulpride concentration (P = 1.3e-05) and D2/3 occupancy (P < .01, caudate, putamen, thalamus). Model predictions suggested that across concentrations of 40-100 ng/mL, and occupancies of 40% to 70% in the caudate and thalamus and 30% to 60% in the putamen, there was a 50% to 90% probability of response and < 30% probability of EPS. Simulations, based on concentration-delusions and concentration-EPS model outputs, showed that 50 mg/d of amisulpride was the appropriate dose to achieve this target range in those aged > 75 years; increasing the dose to 75 mg/d increased the risk of EPS, particularly in those aged > 85 years of low body weight. CONCLUSIONS: These findings argue strongly for the consideration of age- and weight-based dose adjustments in older patients with AD-related psychosis and indicate that 50 mg/d of amisulpride may be both the minimal clinically effective dose and, in those aged > 75 years, the maximally tolerated dose.
[Mh] Termos MeSH primário: Doença de Alzheimer/sangue
Doença de Alzheimer/tratamento farmacológico
Transtornos Psicóticos/sangue
Transtornos Psicóticos/tratamento farmacológico
Sulpirida/análogos & derivados
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/psicologia
Doenças dos Gânglios da Base/sangue
Doenças dos Gânglios da Base/induzido quimicamente
Doenças dos Gânglios da Base/prevenção & controle
Encéfalo/efeitos dos fármacos
Delusões/sangue
Delusões/tratamento farmacológico
Delusões/psicologia
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Masculino
Prolactina/sangue
Transtornos Psicóticos/psicologia
Receptores de Dopamina D2/efeitos dos fármacos
Receptores de Dopamina D3/efeitos dos fármacos
Valores de Referência
Fatores de Risco
Sulpirida/administração & dosagem
Sulpirida/efeitos adversos
Sulpirida/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Dopamine D2); 0 (Receptors, Dopamine D3); 7MNE9M8287 (Sulpiride); 9002-62-4 (Prolactin); AA0G3TW31W (sultopride)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE


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[PMID]:28447882
[Au] Autor:Gamal W; Fahmy RH; Mohamed MI
[Ad] Endereço:a Department of Pharmaceutics, Faculty of Pharmacy , Ahram Canadian University , 6th of October City , Cairo , Egypt.
[Ti] Título:Development of novel amisulpride-loaded solid self-nanoemulsifying tablets: preparation and pharmacokinetic evaluation in rabbits.
[So] Source:Drug Dev Ind Pharm;43(9):1539-1547, 2017 Sep.
[Is] ISSN:1520-5762
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The current investigation is focused on the formulation and in vivo evaluation of optimized solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of amisulpride (AMS) for improving its oral dissolution and bioavailability. METHODS: Liquid SNEDDS (L-SNEDDS) composed of Capryol™ 90 (oil), Cremophor RH40 (surfactant), and Transcutol HP (co-surfactant) were transformed to solid systems via physical adsorption onto magnesium aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state characterization of formulated S-SNEDDS were carried out, followed by tableting, tablet evaluation, and pharmacokinetic studies in rabbits. RESULTS: Micromeretic properties and solid-state characterization proved satisfactory flow properties with AMS present in a completely amorphous state. Formulated self-nanoemulsifying tablets revealed significant improvement in AMS dissolution compared with either directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in rabbits emphasized significant improvements in t , AUC , and AUC at p < .05 with 1.26-folds improvement in relative bioavailability from the optimized self-nanoemulsifying tablets compared with the commercial product. CONCLUSIONS: S-SNEDDS can be a very useful approach for providing patient acceptable dosage forms with improved oral dissolution and biovailability.
[Mh] Termos MeSH primário: Sistemas de Liberação de Medicamentos/métodos
Emulsões/química
Etilenoglicóis/farmacocinética
Polietilenoglicóis/química
Sulpirida/análogos & derivados
Tensoativos/química
[Mh] Termos MeSH secundário: Administração Oral
Animais
Disponibilidade Biológica
Química Farmacêutica
Portadores de Fármacos
Etilenoglicóis/administração & dosagem
Etilenoglicóis/química
Tamanho da Partícula
Coelhos
Sulpirida/administração & dosagem
Sulpirida/química
Sulpirida/farmacocinética
Comprimidos/química
Comprimidos/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Emulsions); 0 (Ethylene Glycols); 0 (Surface-Active Agents); 0 (Tablets); 30IQX730WE (Polyethylene Glycols); 39279-69-1 (cremophor); 7MNE9M8287 (Sulpiride); A1A1I8X02B (carbitol); AA0G3TW31W (sultopride)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1080/03639045.2017.1322608


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[PMID]:28447878
[Au] Autor:Gamal W; Fahmy RH; Mohamed MI
[Ad] Endereço:a Department of Pharmaceutics, Faculty of Pharmacy , Ahram Canadian University , Cairo , Egypt.
[Ti] Título:Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery systems via dual tackling of its solubility and intestinal permeability.
[So] Source:Drug Dev Ind Pharm;43(9):1530-1538, 2017 Sep.
[Is] ISSN:1520-5762
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The aim of the current investigation was at enhancing the oral biopharmaceutical behavior; solubility and intestinal permeability of amisulpride (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) containing bioenhancing excipients. METHODS: The components of L-SNEDDS were identified via solubility studies and emulsification efficiency tests, and ternary phase diagrams were constructed to identify the efficient self-emulsification regions. The formulated systems were assessed for their thermodynamic stability, globule size, self-emulsification time, optical clarity and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique was adopted for uncovering the permeability enhancing effect of the formulated systems. RESULTS: The optimum formulations were composed of different ratios of Capryol™ 90 as an oil phase, Cremophor RH40 as a surfactant, and Transcutol HP as a co-surfactant. All tested formulations were thermodynamically stable with globule sizes ranging from 13.74 to 29.19 nm and emulsification time not exceeding 1 min, indicating the formation of homogenous stable nanoemulsions. In vitro drug release showed significant enhancement from L-SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS showed significantly higher intestinal permeation compared to plain drug solution with nearly 1.6-2.9 folds increase in the apparent permeability coefficient as demonstrated by the ex vivo studies. CONCLUSIONS: The present study proved that AMS could be successfully incorporated into L-SNEDDS for improved dissolution and intestinal permeation leading to enhanced oral delivery.
[Mh] Termos MeSH primário: Sistemas de Liberação de Medicamentos/métodos
Emulsões/química
Etilenoglicóis/administração & dosagem
Absorção Intestinal/fisiologia
Polietilenoglicóis/química
Sulpirida/análogos & derivados
Tensoativos/química
[Mh] Termos MeSH secundário: Administração Oral
Disponibilidade Biológica
Química Farmacêutica
Liberação Controlada de Fármacos
Etilenoglicóis/química
Excipientes/química
Tamanho da Partícula
Permeabilidade
Solubilidade
Sulpirida/administração & dosagem
Sulpirida/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Emulsions); 0 (Ethylene Glycols); 0 (Excipients); 0 (Surface-Active Agents); 30IQX730WE (Polyethylene Glycols); 39279-69-1 (cremophor); 7MNE9M8287 (Sulpiride); A1A1I8X02B (carbitol); AA0G3TW31W (sultopride)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1080/03639045.2017.1322607


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[PMID]:28406051
[Au] Autor:Siddiqui PJA; Khan A; Uddin N; Khaliq S; Rasheed M; Nawaz S; Hanif M; Dar A
[Ad] Endereço:a Centre of Excellence in Marine Biology, University of Karachi , Karachi , Pakistan.
[Ti] Título:Antidepressant-like deliverables from the sea: evidence on the efficacy of three different brown seaweeds via involvement of monoaminergic system.
[So] Source:Biosci Biotechnol Biochem;81(7):1369-1378, 2017 Jul.
[Is] ISSN:1347-6947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Brown seaweeds exhibit several health benefits in treating and managing wide array of ailments. In this study, the antidepressant-like effect of methaolic extracts from Sargassum swartzii (SS), Stoechospermum marginatum (SM), and Nizamuddinia zanardinii (NZ) was examined in forced swimming test (FST), in rats. Oral administration of SS, SM, and NZ extract (30-60 mg/kg) exhibited antidepressant-like activity in FST by reducing immobility time as compared to control group, without inducing significant change in ambulatory behavior in open field test. In order to evaluate the involvement of monoaminergic system, rats were pretreated with the inhibitor of brain serotonin stores p-chlorophenylalanin (PCPA), dopamine (SCH23390 and sulpiride), and adrenoceptor (prazosin and propranolol) antagonists. Rats receiving treatment for 28 days were decapitated and brains were analyzed for monoamine levels. It may be concluded that the extracts of SS, SM, and NZ produces antidepressant-like activity via modulation of brain monoaminergic system in a rat model.
[Mh] Termos MeSH primário: Antidepressivos/farmacologia
Depressão/prevenção & controle
Feófitas/química
Receptores Adrenérgicos/genética
Receptores Dopaminérgicos/genética
Receptores de Serotonina/genética
Alga Marinha/química
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos/farmacologia
Animais
Antidepressivos/isolamento & purificação
Benzazepinas/farmacologia
Depressão/genética
Depressão/metabolismo
Depressão/fisiopatologia
Antagonistas de Dopamina/farmacologia
Fenclonina/farmacologia
Regulação da Expressão Gênica/efeitos dos fármacos
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Metanol
Prazosina/farmacologia
Propranolol/farmacologia
Ratos
Ratos Wistar
Receptores Adrenérgicos/metabolismo
Receptores Dopaminérgicos/metabolismo
Receptores de Serotonina/metabolismo
Antagonistas da Serotonina/farmacologia
Solventes
Sulpirida/farmacologia
Natação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic Antagonists); 0 (Antidepressive Agents); 0 (Benzazepines); 0 (Dopamine Antagonists); 0 (Receptors, Adrenergic); 0 (Receptors, Dopamine); 0 (Receptors, Serotonin); 0 (SCH 23390); 0 (Serotonin Antagonists); 0 (Solvents); 7MNE9M8287 (Sulpiride); 9Y8NXQ24VQ (Propranolol); R5J7E3L9SP (Fenclonine); XM03YJ541D (Prazosin); Y4S76JWI15 (Methanol)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170707
[Lr] Data última revisão:
170707
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1080/09168451.2017.1313697


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[PMID]:28334978
[Au] Autor:Reeves S; McLachlan E; Bertrand J; Antonio FD; Brownings S; Nair A; Greaves S; Smith A; Taylor D; Dunn J; Marsden P; Kessler R; Howard R
[Ad] Endereço:Division of Psychiatry, 149 Tottenham Court Road, London W1T 7NF, University College London, UK.
[Ti] Título:Therapeutic window of dopamine D2/3 receptor occupancy to treat psychosis in Alzheimer's disease.
[So] Source:Brain;140(4):1117-1127, 2017 Apr 01.
[Is] ISSN:1460-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:See Caravaggio and Graff-Guerrero (doi:10.1093/awx023) for a scientific commentary on this article.Antipsychotic drugs, originally developed to treat schizophrenia, are used to treat psychosis, agitation and aggression in Alzheimer's disease. In the absence of dopamine D2/3 receptor occupancy data to inform antipsychotic prescribing for psychosis in Alzheimer's disease, the mechanisms underpinning antipsychotic efficacy and side effects are poorly understood. This study used a population approach to investigate the relationship between amisulpride blood concentration and central D2/3 occupancy in older people with Alzheimer's disease by combining: (i) pharmacokinetic data (280 venous samples) from a phase I single (50 mg) dose study in healthy older people (n = 20, 65-79 years); (ii) pharmacokinetic, 18F-fallypride D2/3 receptor imaging and clinical outcome data on patients with Alzheimer's disease who were prescribed amisulpride (25-75 mg daily) to treat psychosis as part of an open study (n = 28; 69-92 years; 41 blood samples, five pretreatment scans, 19 post-treatment scans); and (iii) 18F-fallypride imaging of an antipsychotic free Alzheimer's disease control group (n = 10, 78-92 years), to provide additional pretreatment data. Non-linear mixed effects modelling was used to describe pharmacokinetic-occupancy curves in caudate, putamen and thalamus. Model outputs were used to estimate threshold steady state blood concentration and occupancy required to elicit a clinically relevant response (>25% reduction in scores on delusions, hallucinations and agitation domains of the Neuropsychiatric Inventory) and extrapyramidal side effects (Simpson Angus Scale scores > 3). Average steady state blood levels were low (71 ± 30 ng/ml), and associated with high D2/3 occupancies (65 ± 8%, caudate; 67 ± 11%, thalamus; 52 ± 11%, putamen). Antipsychotic clinical response occurred at a threshold concentration of 20 ng/ml and D2/3 occupancies of 43% (caudate), 25% (putamen), 43% (thalamus). Extrapyramidal side effects (n = 7) emerged at a threshold concentration of 60 ng/ml, and D2/3 occupancies of 61% (caudate), 49% (putamen) and 69% (thalamus). This study has established that, as in schizophrenia, there is a therapeutic window of D2/3 receptor occupancy for optimal treatment of psychosis in Alzheimer's disease. We have also shown that occupancies within and beyond this window are achieved at very low amisulpride doses in Alzheimer's disease due to higher than anticipated occupancies for a given blood drug concentration. Our findings support a central pharmacokinetic contribution to antipsychotic sensitivity in Alzheimer's disease and implicate the blood-brain barrier, which controls central drug access. Whether high D2/3 receptor occupancies are primarily accounted for by age- or disease-specific blood-brain barrier disruption is unclear, and this is an important future area of future investigation, as it has implications beyond antipsychotic prescribing.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Doença de Alzheimer/psicologia
Antipsicóticos/uso terapêutico
Dopaminérgicos/uso terapêutico
Transtornos Psicóticos/tratamento farmacológico
Transtornos Psicóticos/psicologia
Receptores de Dopamina D2/efeitos dos fármacos
Receptores de Dopamina D3/efeitos dos fármacos
Sulpirida/análogos & derivados
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/diagnóstico por imagem
Antipsicóticos/farmacocinética
Benzamidas
Dopaminérgicos/farmacocinética
Feminino
Seres Humanos
Masculino
Tomografia por Emissão de Pósitrons
Transtornos Psicóticos/diagnóstico por imagem
Pirrolidinas
Fatores Socioeconômicos
Sulpirida/farmacocinética
Sulpirida/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Benzamides); 0 (Dopamine Agents); 0 (N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide); 0 (Pyrrolidines); 0 (Receptors, Dopamine D2); 0 (Receptors, Dopamine D3); 7MNE9M8287 (Sulpiride); AA0G3TW31W (sultopride)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170425
[Lr] Data última revisão:
170425
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/brain/aww359


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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


  7 / 3830 MEDLINE  
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[PMID]:28233634
[Au] Autor:Sasaki-Hamada S; Suzuki A; Ueda Y; Matsumoto K; Oka JI
[Ad] Endereço:Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan.
[Ti] Título:Serotonergic and dopaminergic systems are implicated in antidepressant-like effects of chotosan, a Kampo formula, in mice.
[So] Source:J Pharmacol Sci;133(2):110-113, 2017 Feb.
[Is] ISSN:1347-8648
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:We previously demonstrated that chotosan (CTS), a traditional herbal formula called Kampo medicine, improves diabetes-induced cognitive deficits. In the present study, we investigated the antidepressant-like effects of CTS in mice. The administration of CTS (1.0 g/kg, for 3 days) decreased the immobility time in the forced-swim test, and this decrease was prevented by the prior administration of sulpiride (an antagonist of D receptors) and WAY100635 (an antagonist of 5-HT receptors). None of the treatments tested altered the locomotor activity of mice. These results suggest that CTS exerts antidepressant-like effects through changes in the serotonergic and dopaminergic systems.
[Mh] Termos MeSH primário: Antidepressivos/farmacologia
Dopaminérgicos/farmacologia
Medicamentos de Ervas Chinesas/farmacologia
Medicina Kampo
Serotoninérgicos/farmacologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Fenclonina/química
Imipramina/química
Imipramina/farmacologia
Ketanserina/química
Ketanserina/farmacologia
Locomoção
Masculino
Metergolina/química
Camundongos
Piperazinas/química
Piperazinas/farmacologia
Piridinas/química
Piridinas/farmacologia
Sulpirida/química
Sulpirida/farmacologia
Natação
Ioimbina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Dopamine Agents); 0 (Drugs, Chinese Herbal); 0 (Piperazines); 0 (Pyridines); 0 (Serotonin Agents); 0 (choto-san); 1501393LY5 (Metergoline); 2Y49VWD90Q (Yohimbine); 71IH826FEG (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide); 7MNE9M8287 (Sulpiride); 97F9DE4CT4 (Ketanserin); OGG85SX4E4 (Imipramine); R5J7E3L9SP (Fenclonine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170225
[St] Status:MEDLINE


  8 / 3830 MEDLINE  
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[PMID]:28202786
[Au] Autor:Diederen KM; Ziauddeen H; Vestergaard MD; Spencer T; Schultz W; Fletcher PC
[Ad] Endereço:Department of Psychiatry and k.diederen@gmail.com.
[Ti] Título:Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum.
[So] Source:J Neurosci;37(7):1708-1720, 2017 Feb 15.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness. To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that are modulated by the brain chemical dopamine are sensitive to reward variability. Here, we aimed to directly relate dopamine to learning about variable rewards, and the neural encoding of associated teaching signals. We perturbed dopamine in healthy individuals using dopaminergic medication and asked them to predict variable rewards while we made brain scans. Dopamine perturbations impaired learning and the neural encoding of reward variability, thus establishing a direct link between dopamine and adaptation to reward variability. These results aid our understanding of clinical conditions associated with dopaminergic dysfunction, such as psychosis.
[Mh] Termos MeSH primário: Adaptação Fisiológica/fisiologia
Corpo Estriado/metabolismo
Mesencéfalo/metabolismo
[Mh] Termos MeSH secundário: Adaptação Fisiológica/efeitos dos fármacos
Adulto
Bromocriptina/farmacologia
Simulação por Computador
Corpo Estriado/diagnóstico por imagem
Corpo Estriado/efeitos dos fármacos
Agonistas de Dopamina/farmacologia
Antagonistas de Dopamina/farmacologia
Método Duplo-Cego
Feminino
Testes Genéticos
Voluntários Saudáveis
Seres Humanos
Processamento de Imagem Assistida por Computador
Masculino
Mesencéfalo/diagnóstico por imagem
Mesencéfalo/efeitos dos fármacos
Motivação/efeitos dos fármacos
Motivação/fisiologia
Oxigênio/sangue
Recompensa
Sulpirida/farmacologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Dopamine Agonists); 0 (Dopamine Antagonists); 3A64E3G5ZO (Bromocriptine); 7MNE9M8287 (Sulpiride); S88TT14065 (Oxygen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.1979-16.2016


  9 / 3830 MEDLINE  
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[PMID]:28069917
[Au] Autor:Kahnt T; Tobler PN
[Ad] Endereço:Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, and thorsten.kahnt@northwestern.edu.
[Ti] Título:Dopamine Modulates the Functional Organization of the Orbitofrontal Cortex.
[So] Source:J Neurosci;37(6):1493-1504, 2017 Feb 08.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks. A key role of any neuromodulator may be the reconfiguration of functional brain circuits. Here we test this idea with regard to dopamine and the organization of functional networks in the orbitofrontal cortex (OFC). We show that blockade of dopamine D receptors has profound effects on the functional connectivity patterns of the OFC, yielding altered connectivity-based subdivisions of this region. Our results suggest that dopamine changes the connectional configuration of the OFC, possibly leading to transitions between different operating modes that favor either sensory input or recurrent processing in the prefrontal cortex. More generally, our findings support a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks and may have clinical implications for understanding the actions of antipsychotic agents.
[Mh] Termos MeSH primário: Antagonistas de Dopamina/farmacologia
Dopamina/fisiologia
Imagem por Ressonância Magnética/métodos
Rede Nervosa/fisiologia
Córtex Pré-Frontal/fisiologia
Receptores de Dopamina D2/fisiologia
[Mh] Termos MeSH secundário: Método Duplo-Cego
Seres Humanos
Masculino
Rede Nervosa/efeitos dos fármacos
Córtex Pré-Frontal/efeitos dos fármacos
Distribuição Aleatória
Sulpirida/análogos & derivados
Sulpirida/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dopamine Antagonists); 0 (Receptors, Dopamine D2); 7MNE9M8287 (Sulpiride); AA0G3TW31W (sultopride); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170111
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.2827-16.2016


  10 / 3830 MEDLINE  
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[PMID]:27977467
[Au] Autor:Chan HY; Pan YJ; Chen JJ; Chen CH
[Ad] Endereço:From the *Department of General Psychiatry, Taoyuan Psychiatric Center, Taoyuan; and †Department of Psychiatry, National Taiwan University Hospital and School of Medicine, National Taiwan University; ‡Department of Psychiatry, Far Eastern Memorial Hospital; and §Department of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
[Ti] Título:Time to Discontinuation of Second-Generation Antipsychotics Versus Haloperidol and Sulpiride in People With Schizophrenia: A Naturalistic, Comparative Study.
[So] Source:J Clin Psychopharmacol;37(1):13-20, 2017 Feb.
[Is] ISSN:1533-712X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: A retrospective study was conducted to evaluate the time to discontinuation (TTD) of the first- (FGAs) and second-generation antipsychotics (SGAs). METHODS: In total, 918 treatment episodes of patients with schizophrenia, initiated on one of the investigated drugs on an outpatient basis during 2004-2006, were entered into the study. The primary outcome was the duration of the investigated treatment episode. Discontinuation was defined when either patients were admitted or the investigated drug had been stopped for more than 28 days. We used the Cox proportional hazard model to compare hazards of discontinuations among 8 SGAs versus 2 FGAs (haloperidol and sulpiride). The follow-up period was up to 18 months. RESULTS: During the follow-up period, clozapine had the highest rate of continuous treatment in the primary analysis: clozapine, 40.6%; olanzapine, 23.4%; aripiprazole, 22.9%; amisulpride, 21.9%; zotepine, 21.3%; sulpiride, 17.0%; risperidone, 12.8%; quetiapine, 12.5%; haloperidol, 10.6%; and ziprasidone, 10.4%. Compared with haloperidol, 5 SGAs had significantly longer TTD (adjusted hazard ratios and 95% confidence intervals): clozapine (0.403, 0.267-0.607), olanzapine (0.611, 0.439-0.849), aripiprazole (0.570, 0.407-0.795), amisulpride (0.680, 0.487-0.947), and zotepine (0.687, 0.497-0.948), but only clozapine had significantly longer TTD compared with sulpiride (0.519, 0.342-0.786). The sensitivity analysis showed similar results. IMPLICATIONS/CONCLUSIONS: The current findings suggested that SGAs or FGAs are not homogeneous groups. Clozapine has the highest rate of continuous treatment among SGAs, and haloperidol is not the representative drug for all FGAs. Furthermore, antipsychotics dropout rate is high in naturalistic situation. A good service model needs to be constructed to enhance antipsychotic treatment adherence of people with schizophrenia.
[Mh] Termos MeSH primário: Antipsicóticos/administração & dosagem
Clozapina/administração & dosagem
Haloperidol/administração & dosagem
Adesão à Medicação/estatística & dados numéricos
Esquizofrenia/tratamento farmacológico
Sulpirida/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Estudos Retrospectivos
Taiwan
Fatores de Tempo
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 7MNE9M8287 (Sulpiride); J60AR2IKIC (Clozapine); J6292F8L3D (Haloperidol)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE
[do] DOI:10.1097/JCP.0000000000000623



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