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[PMID]:28697173
[Au] Autor:Kuzu OF; Gowda R; Noory MA; Robertson GP
[Ad] Endereço:Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
[Ti] Título:Modulating cancer cell survival by targeting intracellular cholesterol transport.
[So] Source:Br J Cancer;117(4):513-524, 2017 Aug 08.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Demand for cholesterol is high in certain cancers making them potentially sensitive to therapeutic strategies targeting cellular cholesterol homoeostasis. A potential approach involves disruption of intracellular cholesterol transport, which occurs in Niemann-Pick disease as a result of acid sphingomyelinase (ASM) deficiency. Hence, a class of lysosomotropic compounds that were identified as functional ASM inhibitors (FIASMAs) might exhibit chemotherapeutic activity by disrupting cancer cell cholesterol homoeostasis. METHODS: Here, the chemotherapeutic utility of ASM inhibition was investigated. The effect of FIASMAs on intracellular cholesterol levels, cholesterol homoeostasis, cellular endocytosis and signalling cascades were investigated. The in vivo efficacy of ASM inhibition was demonstrated using melanoma xenografts and a nanoparticle formulation was developed to overcome dose-limiting CNS-associated side effects of certain FIASMAs. RESULTS: Functional ASM inhibitors inhibited intracellular cholesterol transport leading to disruption of autophagic flux, cellular endocytosis and receptor tyrosine kinase signalling. Consequently, major oncogenic signalling cascades on which cancer cells were reliant for survival were inhibited. Two tested ASM inhibitors, perphenazine and fluphenazine that are also clinically used as antipsychotics, were effective in inhibiting xenografted tumour growth. Nanoliposomal encapsulation of the perphenazine enhanced its chemotherapeutic efficacy while decreasing CNS-associated side effects. CONCLUSIONS: This study suggests that disruption of intracellular cholesterol transport by targeting ASM could be utilised as a potential chemotherapeutic approach for treating cancer.
[Mh] Termos MeSH primário: Antidepressivos Tricíclicos/farmacologia
Antipsicóticos/farmacologia
Colesterol/metabolismo
Melanoma/tratamento farmacológico
Melanoma/metabolismo
Perfenazina/administração & dosagem
[Mh] Termos MeSH secundário: Administração Intravenosa
Administração Oral
Animais
Antidepressivos Tricíclicos/uso terapêutico
Antipsicóticos/administração & dosagem
Autofagia/efeitos dos fármacos
Transporte Biológico/efeitos dos fármacos
Transporte Biológico/genética
Sobrevivência Celular/efeitos dos fármacos
Desipramina/farmacologia
Desipramina/uso terapêutico
Endocitose/efeitos dos fármacos
Endossomos/metabolismo
Feminino
Flupentixol/farmacologia
Flupentixol/uso terapêutico
Flufenazina/farmacologia
Flufenazina/uso terapêutico
Regulação da Expressão Gênica/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Células HCT116
Homeostase/efeitos dos fármacos
Homeostase/genética
Seres Humanos
Concentração Inibidora 50
Lipossomos
Lisossomos/metabolismo
Lisossomos/ultraestrutura
Células MCF-7
Melanoma/genética
Camundongos
Nortriptilina/farmacologia
Nortriptilina/uso terapêutico
Perfenazina/farmacologia
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais/efeitos dos fármacos
Esfingomielina Fosfodiesterase/genética
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents, Tricyclic); 0 (Antipsychotic Agents); 0 (Liposomes); 0 (STAT3 Transcription Factor); 0 (bcl-2-Associated X Protein); 97C5T2UQ7J (Cholesterol); BL03SY4LXB (Nortriptyline); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.4.12 (Sphingomyelin Phosphodiesterase); EC 3.1.4.12 (sphingomyelin phosphodiesterase 1, human); FA0UYH6QUO (Flupenthixol); FTA7XXY4EZ (Perphenazine); S79426A41Z (Fluphenazine); TG537D343B (Desipramine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.200


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[PMID]:28537967
[Au] Autor:Mi W; Wang S; You Z; Lim G; McCabe MF; Kim H; Chen L; Mao J
[Ad] Endereço:From the *MGH Center for Translational Pain Research and Division of Pain Medicine, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and †Department of Integrative Medicine and Neurobiology, ‡Institute of Acupuncture and Moxibustion, §Fudan Institutes of Integrative Medicine, ‖School of Basic Medical Sciences, and ¶Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
[Ti] Título:Nortriptyline Enhances Morphine-Conditioned Place Preference in Neuropathic Rats: Role of the Central Noradrenergic System.
[So] Source:Anesth Analg;125(3):1032-1041, 2017 Sep.
[Is] ISSN:1526-7598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Combination drug therapy is commonly used to treat chronic pain conditions such as neuropathic pain, and antidepressant is often used together with opioid analgesics. While rewarding is an intrinsic property of opioid analgesics, it is unknown whether the use of an antidepressant would influence opioid reward, which may contribute to opioid addiction. In this study, we examined whether nortriptyline (a tricyclic antidepressant and a first-line medication for neuropathic pain) would enhance the morphine rewarding property in both naive and chronic constriction sciatic nerve injury (CCI) rats. METHODS: The rewarding effect of these drugs was assessed using conditioned place preference (CPP). The real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay analysis were used to investigate the function of central noradrenergic system. RESULTS: In naive rats, coadministration of nortriptyline with morphine did not change the acquisition of morphine-induced CPP. However, nortriptyline enhanced the acquisition, delayed the extinction, and augmented the reinstatement of morphine-induced CPP in CCI rats. In CCI rats treated with both nortriptyline and morphine, the expression of α2A-adrenergic receptors, norepinephrine transporter, and tyrosine hydroxylase was markedly decreased in the locus coeruleus, whereas the norepinephrine concentration in the nucleus accumbens was remarkably increased. CONCLUSIONS: These results demonstrate that nortriptyline enhanced morphine reward when both drugs were used to treat neuropathic pain in rats and that this behavioral phenotype is likely to be mediated by upregulation of the central noradrenergic system. These findings may have implications in opioid therapy commonly used for chronic pain management.
[Mh] Termos MeSH primário: Condicionamento Operante/efeitos dos fármacos
Morfina/administração & dosagem
Neuralgia/tratamento farmacológico
Neuralgia/metabolismo
Norepinefrina/metabolismo
Nortriptilina/administração & dosagem
[Mh] Termos MeSH secundário: Neurônios Adrenérgicos/efeitos dos fármacos
Neurônios Adrenérgicos/metabolismo
Analgésicos Opioides/administração & dosagem
Animais
Condicionamento Operante/fisiologia
Quimioterapia Combinada
Masculino
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 76I7G6D29C (Morphine); BL03SY4LXB (Nortriptyline); X4W3ENH1CV (Norepinephrine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1213/ANE.0000000000002128


  3 / 2042 MEDLINE  
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[PMID]:28381364
[Au] Autor:Slampová A; Kubán P
[Ad] Endereço:Institute of Analytical Chemistry of the Czech Academy of Sciences, v. v. i., Veverí 97, CZ-60200 Brno, Czech Republic.
[Ti] Título:Injections from sub-µL sample volumes in commercial capillary electrophoresis.
[So] Source:J Chromatogr A;1497:164-171, 2017 May 12.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A simple sample injection procedure compatible with commercial capillary electrophoresis (CE) instrumentation was developed, which enables handling sample volumes as little as 250nL for analytical applications where sample volume availability is of concern. Single-use micro-sampling inserts were prepared by thermal modification of polypropylene micropipette tips and the inserts were accommodated in standard CE vials in CE autosampler carousel. To ensure direct contact of separation capillary injection end with sample solution and to avoid possible damage to the capillary, a soft compression spring was placed at the bottom of the vial underneath the micro-sampling insert. Injections from sub-µL samples were carried out in conventional as well as in short-end injection mode, were compatible with standard i.d./o.d. (25-100µm/365µm) fused silica capillaries and with various background electrolyte solutions and detection modes. Excellent repeatability of replicate injections from 250nL to 3µL was achieved based on RSD values of quantitative analytical measures (peak heights ≤2.4% and peak areas ≤3.7%) for CE-UV-vis, CE-ESI-MS and CE-contactless conductivity detection of model basic drugs. The achieved RSD values were comparable with those for replicate injections of the drugs from standard CE vials. The reported concept of injections from micro-sampling inserts was further demonstrated useful in evaluation of micro-electromembrane extraction (µ-EME) of model basic drugs. Sub-µL volumes of operational solutions resulted in reduced lengths of µ-EME phases and improved extraction recoveries (66-91%) were achieved.
[Mh] Termos MeSH primário: Eletroforese Capilar/métodos
[Mh] Termos MeSH secundário: Eletrólitos/química
Eletroforese Capilar/instrumentação
Espectrometria de Massas
Nortriptilina/análise
Nortriptilina/isolamento & purificação
Papaverina/análise
Soluções/química
Espectrofotometria Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Electrolytes); 0 (Solutions); BL03SY4LXB (Nortriptyline); DAA13NKG2Q (Papaverine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170516
[Lr] Data última revisão:
170516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE


  4 / 2042 MEDLINE  
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[PMID]:28099119
[Au] Autor:van der Hagen EAE; Smeekens KCJ; van 't Veer NE; Boonen KJM; Ermens AAM
[Ad] Endereço:.
[Ti] Título:Interference in Na+ measurements on the Siemens RAPIDPoint® 500 after nortriptyline intoxication: a case report.
[So] Source:Clin Chem Lab Med;55(9):e199-e201, 2017 08 28.
[Is] ISSN:1437-4331
[Cp] País de publicação:Germany
[La] Idioma:eng
[Mh] Termos MeSH primário: Gasometria
Nortriptilina/metabolismo
Sódio/análise
[Mh] Termos MeSH secundário: Análise Química do Sangue
Gasometria/instrumentação
Transtorno Depressivo/patologia
Eletrocardiografia
Feminino
Seres Humanos
Meia-Idade
Nortriptilina/análise
Transtornos Psicóticos/patologia
[Pt] Tipo de publicação:CASE REPORTS; LETTER
[Nm] Nome de substância:
9NEZ333N27 (Sodium); BL03SY4LXB (Nortriptyline)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE


  5 / 2042 MEDLINE  
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[PMID]:27730651
[Au] Autor:Ghavami Y; Haidar YM; Ziai KN; Moshtaghi O; Bhatt J; Lin HW; Djalilian HR
[Ad] Endereço:Division of Otology, Neurotology, and Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, University of California, Irvine, Irvine, California, U.S.A.
[Ti] Título:Management of mal de debarquement syndrome as vestibular migraines.
[So] Source:Laryngoscope;127(7):1670-1675, 2017 Jul.
[Is] ISSN:1531-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Mal de debarquement syndrome (MdDS) is a balance disorder that typically starts after an extended exposure to passive motion, such as a boat or plane ride. Management is typically supportive (e.g. physical therapy), and symptoms that persist beyond 6 months have been described as unlikely to remit. This study was conducted to evaluate the response of patients with MdDS to management with migraine prophylaxis, including lifestyle changes and medical therapy. STUDY DESIGN: Prospective review. SETTING: Ambulatory setting at a tertiary care medical center. METHODS: Clinical history, detailed questionnaires, and audiograms were used to diagnose patients with MdDS. Those patients with the diagnosis of the MdDS were placed on our institutional vestibular migraine management protocol. Treatment response was assessed with a quality-of-life (QOL) survey and visual analog scale. RESULTS: Fifteen patients were diagnosed with MdDS, with a predominance of females (73%) and a mean age of 50 ± 13 years. Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof. In comparison, a retrospective control group of 17 patients demonstrated a lower rate of improvement when treated with vestibular rehabilitation and physical therapy. CONCLUSION: Management of MdDS as vestibular migraine can improve patients' symptoms and increase the QOL. Nearly all the patients suffering from MdDS had a personal or family history of migraine headaches or had signs or symptoms suggestive of atypical migraine. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1670-1675, 2017.
[Mh] Termos MeSH primário: Frutose/análogos & derivados
Doença de Meniere/tratamento farmacológico
Transtornos de Enxaqueca/tratamento farmacológico
Enjoo devido ao Movimento/tratamento farmacológico
Nortriptilina/uso terapêutico
Verapamil/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Quimioterapia Combinada
Feminino
Frutose/uso terapêutico
Predisposição Genética para Doença/genética
Seres Humanos
Masculino
Doença de Meniere/diagnóstico
Doença de Meniere/genética
Meia-Idade
Transtornos de Enxaqueca/diagnóstico
Transtornos de Enxaqueca/genética
Enjoo devido ao Movimento/diagnóstico
Enjoo devido ao Movimento/genética
Estudos Prospectivos
Qualidade de Vida
Viagem
Escala Visual Analógica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0H73WJJ391 (topiramate); 30237-26-4 (Fructose); BL03SY4LXB (Nortriptyline); CJ0O37KU29 (Verapamil)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161013
[St] Status:MEDLINE
[do] DOI:10.1002/lary.26299


  6 / 2042 MEDLINE  
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[PMID]:27696737
[Au] Autor:Malki K; Tosto MG; Mouriño-Talín H; Rodríguez-Lorenzo S; Pain O; Jumhaboy I; Liu T; Parpas P; Newman S; Malykh A; Carboni L; Uher R; McGuffin P; Schalkwyk LC; Bryson K; Herbster M
[Ad] Endereço:King's College London, MRC Social, Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry, Psychology and Neuroscience (IOPPN), London, United Kingdom.
[Ti] Título:Highly polygenic architecture of antidepressant treatment response: Comparative analysis of SSRI and NRI treatment in an animal model of depression.
[So] Source:Am J Med Genet B Neuropsychiatr Genet;174(3):235-250, 2017 Apr.
[Is] ISSN:1552-485X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Response to antidepressant (AD) treatment may be a more polygenic trait than previously hypothesized, with many genetic variants interacting in yet unclear ways. In this study we used methods that can automatically learn to detect patterns of statistical regularity from a sparsely distributed signal across hippocampal transcriptome measurements in a large-scale animal pharmacogenomic study to uncover genomic variations associated with AD. The study used four inbred mouse strains of both sexes, two drug treatments, and a control group (escitalopram, nortriptyline, and saline). Multi-class and binary classification using Machine Learning (ML) and regularization algorithms using iterative and univariate feature selection methods, including InfoGain, mRMR, ANOVA, and Chi Square, were used to uncover genomic markers associated with AD response. Relevant genes were selected based on Jaccard distance and carried forward for gene-network analysis. Linear association methods uncovered only one gene associated with drug treatment response. The implementation of ML algorithms, together with feature reduction methods, revealed a set of 204 genes associated with SSRI and 241 genes associated with NRI response. Although only 10% of genes overlapped across the two drugs, network analysis shows that both drugs modulated the CREB pathway, through different molecular mechanisms. Through careful implementation and optimisations, the algorithms detected a weak signal used to predict whether an animal was treated with nortriptyline (77%) or escitalopram (67%) on an independent testing set. The results from this study indicate that the molecular signature of AD treatment may include a much broader range of genomic markers than previously hypothesized, suggesting that response to medication may be as complex as the pathology. The search for biomarkers of antidepressant treatment response could therefore consider a higher number of genetic markers and their interactions. Through predominately different molecular targets and mechanisms of action, the two drugs modulate the same Creb1 pathway which plays a key role in neurotrophic responses and in inflammatory processes. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Antidepressivos/uso terapêutico
Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia
[Mh] Termos MeSH secundário: Animais
Citalopram/uso terapêutico
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
Depressão/tratamento farmacológico
Transtorno Depressivo/tratamento farmacológico
Transtorno Depressivo/genética
Modelos Animais de Doenças
Feminino
Hipocampo
Masculino
Camundongos
Herança Multifatorial/genética
Nortriptilina/uso terapêutico
Farmacogenética
Inibidores da Captação de Serotonina/uso terapêutico
Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico
Transcriptoma/genética
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Creb1 protein, mouse); 0 (Cyclic AMP Response Element-Binding Protein); 0 (Serotonin Uptake Inhibitors); 0 (Serotonin and Noradrenaline Reuptake Inhibitors); 0DHU5B8D6V (Citalopram); BL03SY4LXB (Nortriptyline)
[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:161004
[St] Status:MEDLINE
[do] DOI:10.1002/ajmg.b.32494


  7 / 2042 MEDLINE  
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[PMID]:27147301
[Au] Autor:Yazdani I; Ghazi-Khansari M; Saeedi Saravi SS; Nobakht M; Majdani R; Rezayat SM; Mousavi SE; Yari A; Dehpour AR
[Ad] Endereço:Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Título:Nortriptyline protects testes against germ cell apoptosis and oxidative stress induced by testicular ischaemia/reperfusion.
[So] Source:Andrologia;49(2), 2017 Mar.
[Is] ISSN:1439-0272
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:We designed this experiment to evaluate the effects of nortriptyline on testicular injury after torsion/detorsion (T/D). Ninety-six adult Wistar rats were divided into six groups 16 each in control group (Group 1), sham operated (Group 2), T/D + saline (Group 3), and in groups 4-6; were administered 2, 10 and 20 mg kg , i.p. of nortriptyline 30 and 90 min after torsion respectively. Testicular torsion was created by twisting the right testis 720° in clockwise direction for 1 h. In six rats of each group, tissue MDA level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in compared with control group 4 h after detorsion (P < 0.001). In six rats of each group 24 h after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubules diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in rest of rats. Pre- and post-reperfusion nortriptyline could reduce MDA and caspase-3 levels and normalise antioxidant enzymes activities, dose dependently. Germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, were significantly improved. Inhibition of mitochondrial permeability transition pore is probably involved in protective effects of nortriptyline against testicular T/D cell damages.
[Mh] Termos MeSH primário: Inibidores da Captação Adrenérgica/farmacologia
Apoptose/efeitos dos fármacos
Citoproteção
Nortriptilina/farmacologia
Estresse Oxidativo/efeitos dos fármacos
Traumatismo por Reperfusão/prevenção & controle
Torção do Cordão Espermático/complicações
Espermatozoides/efeitos dos fármacos
Testículo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Inibidores da Captação Adrenérgica/administração & dosagem
Animais
Caspase 3/metabolismo
Catalase/metabolismo
Modelos Animais de Doenças
Glutationa Peroxidase/metabolismo
Seres Humanos
Marcação In Situ das Extremidades Cortadas
Masculino
Malondialdeído/metabolismo
Nortriptilina/administração & dosagem
Ratos
Ratos Wistar
Traumatismo por Reperfusão/etiologia
Traumatismo por Reperfusão/patologia
Contagem de Espermatozoides
Torção do Cordão Espermático/patologia
Espermatozoides/patologia
Superóxido Dismutase/metabolismo
Testículo/irrigação sanguínea
Testículo/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic Uptake Inhibitors); 4Y8F71G49Q (Malondialdehyde); BL03SY4LXB (Nortriptyline); EC 1.11.1.6 (Catalase); EC 1.11.1.9 (Glutathione Peroxidase); EC 1.15.1.1 (Superoxide Dismutase); EC 3.4.22.- (Casp3 protein, rat); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170302
[Lr] Data última revisão:
170302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160506
[St] Status:MEDLINE
[do] DOI:10.1111/and.12605


  8 / 2042 MEDLINE  
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[PMID]:28033366
[Au] Autor:Berm EJ; Gout-Zwart JJ; Luttjeboer J; Wilffert B; Postma MJ
[Ad] Endereço:University of Groningen, Groningen Institute of Pharmacy, Unit of PharmacoTherapy, -Epidemiology and -Economics (PTE2), Groningen, the Netherlands.
[Ti] Título:A Model Based Cost-Effectiveness Analysis of Routine Genotyping for CYP2D6 among Older, Depressed Inpatients Starting Nortriptyline Pharmacotherapy.
[So] Source:PLoS One;11(12):e0169065, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Genotyping for CYP2D6 has the potential to predict differences in metabolism of nortriptyline. This information could optimize pharmacotherapy. We determined the costs and effects of routine genotyping for old aged Dutch depressed inpatients. METHODS: With a decision-tree, we modelled the first 12 weeks of nortriptyline therapy. Direct costs of genotyping, hospitalization, therapeutic drug monitoring and drugs were included. Based on genotype, patients could be correctly, sub-, or supratherapeutically dosed. Improvement from sub- or supratherapeutically dosed patients to correctly dosed patients was simulated, assuming that genotyping would prevent under- or overdosing of patients. In the base case, this improvement was assumed to be 35%. A probabilistic sensitivity analysis (PSA) was performed to determine uncertainty around the incremental cost-effectiveness ratio (ICER). RESULTS: In the base case analysis, costs for genotyping were assumed €200 per test with a corresponding ICER at €1 333 000 per QALY. To reach a €50 000 per QALY cut-off, genotyping costs should be decreased towards €40 per test. At genotyping test costs < €35 per test, genotyping was dominant. At test costs of €17 per test there was a 95% probability that genotyping was cost-effective at €50 000 per QALY. CONCLUSIONS: CYP2D6 genotyping was not cost-effective at current genotyping costs at a €50 000 per QALY threshold, however at test costs below €40, genotyping could be costs-effective.
[Mh] Termos MeSH primário: Análise Custo-Benefício
Citocromo P-450 CYP2D6/genética
Depressão/tratamento farmacológico
Depressão/genética
Técnicas de Genotipagem/economia
Nortriptilina/uso terapêutico
[Mh] Termos MeSH secundário: Árvores de Decisões
Depressão/enzimologia
Relação Dose-Resposta a Droga
Hospitalização
Seres Humanos
Meia-Idade
Modelos Teóricos
Nortriptilina/efeitos adversos
Probabilidade
Anos de Vida Ajustados por Qualidade de Vida
Segurança
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
BL03SY4LXB (Nortriptyline); EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170705
[Lr] Data última revisão:
170705
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161230
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169065


  9 / 2042 MEDLINE  
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[PMID]:27289172
[Au] Autor:Cipriani A; Zhou X; Del Giovane C; Hetrick SE; Qin B; Whittington C; Coghill D; Zhang Y; Hazell P; Leucht S; Cuijpers P; Pu J; Cohen D; Ravindran AV; Liu Y; Michael KD; Yang L; Liu L; Xie P
[Ad] Endereço:Department of Psychiatry, University of Oxford, Oxford, UK. Electronic address: andrea.cipriani@psych.ox.ac.uk.
[Ti] Título:Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis.
[So] Source:Lancet;388(10047):881-90, 2016 Aug 27.
[Is] ISSN:1474-547X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. METHODS: We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. FINDINGS: We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference -0·51, 95% credible interval [CrI] -0·99 to -0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I(2) values were 33·21% for efficacy and 0% for tolerability. INTERPRETATION: When considering the risk-benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated. FUNDING: National Basic Research Program of China (973 Program).
[Mh] Termos MeSH primário: Antidepressivos/administração & dosagem
Antidepressivos/efeitos adversos
Transtorno Depressivo Maior/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Amitriptilina/administração & dosagem
Amitriptilina/efeitos adversos
Teorema de Bayes
Criança
Citalopram/administração & dosagem
Citalopram/efeitos adversos
Clomipramina/administração & dosagem
Clomipramina/efeitos adversos
Fatores de Confusão (Epidemiologia)
Desipramina/administração & dosagem
Desipramina/efeitos adversos
Método Duplo-Cego
Esquema de Medicação
Cloridrato de Duloxetina/administração & dosagem
Cloridrato de Duloxetina/efeitos adversos
Medicina Baseada em Evidências
Fluoxetina/administração & dosagem
Fluoxetina/efeitos adversos
Seres Humanos
Imipramina/administração & dosagem
Imipramina/efeitos adversos
Mianserina/administração & dosagem
Mianserina/efeitos adversos
Mianserina/análogos & derivados
Nortriptilina/administração & dosagem
Nortriptilina/efeitos adversos
Paroxetina/administração & dosagem
Paroxetina/efeitos adversos
Ensaios Clínicos Controlados Aleatórios como Assunto
Projetos de Pesquisa
Sertralina/administração & dosagem
Sertralina/efeitos adversos
Resultado do Tratamento
Triazóis/administração & dosagem
Triazóis/efeitos adversos
Cloridrato de Venlafaxina/administração & dosagem
Cloridrato de Venlafaxina/efeitos adversos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Triazoles); 01K63SUP8D (Fluoxetine); 0DHU5B8D6V (Citalopram); 1806D8D52K (Amitriptyline); 250PJI13LM (Mianserin); 41VRH5220H (Paroxetine); 59H4FCV1TF (nefazodone); 7D7RX5A8MO (Venlafaxine Hydrochloride); 9044SC542W (Duloxetine Hydrochloride); A051Q2099Q (mirtazapine); BL03SY4LXB (Nortriptyline); NUV44L116D (Clomipramine); OGG85SX4E4 (Imipramine); QUC7NX6WMB (Sertraline); TG537D343B (Desipramine)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:171112
[Lr] Data última revisão:
171112
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160613
[St] Status:MEDLINE


  10 / 2042 MEDLINE  
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[PMID]:27101231
[Au] Autor:Berm E; Kok R; Hak E; Wilffert B
[Ad] Endereço:Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, Netherlands.
[Ti] Título:Relation between CYP2D6 Genotype, Phenotype and Therapeutic Drug Concentrations among Nortriptyline and Venlafaxine Users in Old Age Psychiatry.
[So] Source:Pharmacopsychiatry;49(5):186-190, 2016 Sep.
[Is] ISSN:1439-0795
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the metabolite/mother compound ratio. Genotypes were assessed by the *3 and *4 alleles. Data was available from 81 patients (41 nortriptyline, 40 venlafaxine) with a mean age of 72 years. No phenoconversion from poor metabolizers (PM) to extensive metabolizers (EM), or vice versa, was found. However, we did find phenoconversion from PM to intermediate metabolizers (IM), IM to EM, or vice versa in 36% of observations. Among nortriptyline users, patients with a PM or IM genotype had more supra-therapeutic blood levels, although this did not reach statistical significance. In exploratory analyses we found men were more likely (RR: 2.4; 95% CI: 1.14-5.07) to display phenoconversion from an IM genotype to EM phenotype. In addition, compared to non-PMs, PMs were found to have higher risk (RR: 1.56; 95% CI: 1.03-2.37) on non-response, although this was only significant when response was measured on the Hamilton Rating Scale for Depression and not on the Montgomery Åsberg Depression Rating Scale. Patients phenoconversed, but we did not observe phenoconversion from PM to EM or vice versa. Genotype information could be used as a valuable tool, in addition to therapeutic drug monitoring, to prevent supratherapeutic drug levels of nortriptyline or venlafaxine in elderly patients with a PM genotype.
[Mh] Termos MeSH primário: Antidepressivos/uso terapêutico
Citocromo P-450 CYP2D6/genética
Transtorno Depressivo Maior
Nortriptilina/uso terapêutico
Cloridrato de Venlafaxina/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Transtorno Depressivo Maior/tratamento farmacológico
Transtorno Depressivo Maior/genética
Transtorno Depressivo Maior/metabolismo
Relação Dose-Resposta a Droga
Monitoramento de Medicamentos
Feminino
Genótipo
Seres Humanos
Masculino
Meia-Idade
Fenótipo
Medicina de Precisão
Valor Preditivo dos Testes
Escalas de Graduação Psiquiátrica
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antidepressive Agents); 7D7RX5A8MO (Venlafaxine Hydrochloride); BL03SY4LXB (Nortriptyline); EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170306
[Lr] Data última revisão:
170306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160422
[St] Status:MEDLINE



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