Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.507
Filtrar
1.
Nervenarzt ; 91(1): 34-42, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31919550

RESUMO

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


Assuntos
Antipsicóticos , Esquizofrenia , Adulto , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Humanos , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
2.
Postgrad Med ; 132(1): 80-90, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31813311

RESUMO

Objective: Based on a substantial literature, olanzapine appears to be one of the most efficacious antipsychotics marketed in the United States, with only clozapine clearly more advantageous. However, olanzapine is marred by an equally substantial literature demonstrating a metabolic burden of olanzapine, particularly for weight gain. With the publication of successful strategies to limit olanzapine induced weight gain, a reassessment of the clinical utility of olanzapine appears warranted. The purpose of this paper is to review recent evidence for olanzapine, highlighting use in both schizophrenia and other conditions, safety and supporting the use of olanzapine above 20 mg/day, focusing on studies published since our previous reviews in 2008 and 2009.Data Sources: The US National Library of Medicine's PubMed resource (https://www.ncbi.nlm.nih.gov/pubmed/) was searched using the text word 'olanzapine' for all English-language articles published between 2008 to July 2019, inclusive with a specific focus on double-blind randomized controlled trials and meta-analyses. In addition, we examined the review articles for other reports of interest that may have been missed by our initial search.Data Extraction: The studies were evaluated based on efficacy and safety data.Results: Use of olanzapine may be decreasing but remains common overall. Evidence continues to support both the relative efficacy advantage and weight gain/metabolic disadvantages of olanzapine in schizophrenia, and recent research supports olanzapine's use in treating anorexia nervosa and chemotherapy-induced nausea. The evidence for high dose olanzapine dosages >20 mg remains limited. Non-pharmacological options, such as dietary counseling and exercise, appear to be efficacious in addressing antipsychotic-induced weight gain. Topiramate, metformin and possibly the olanzapine-samidorphan combination also appear helpful.Conclusions: Olanzapine remains a useful antipsychotic, but requires with careful monitoring. Further research is needed to compare the different options available to mitigate olanzapine-induced weight gain and to evaluate potential synergism between pharmacological and non-pharmacological treatments.


Assuntos
Antipsicóticos/uso terapêutico , Olanzapina/uso terapêutico , Anorexia Nervosa/tratamento farmacológico , Antipsicóticos/administração & dosagem , Humanos , Náusea/tratamento farmacológico , Olanzapina/administração & dosagem , Esquizofrenia/tratamento farmacológico
5.
Neurol Neurochir Pol ; 53(6): 408-412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681966

RESUMO

The prevalence of various psychiatric disorders in people with epilepsy is high, with psychoses affecting 2-9% of patients. Antipsychotic drugs have been identified as increasing the risk of epileptic seizures. For first-generation antipsychotics such a risk appears to be relatively low, with the exception of chlorpromazine. Among second-generation antipsychotics, clozapine use carries the highest risk of seizure induction, while risperidone, quetiapine, amisulpride, and aripiprazole seem to pose a significantly lower risk. The incidence of an increased number of seizures is linked to the elevated blood plasma level effect of antipsychotics. To diminish the risk of seizures, it is important to start with a small dose of antipsychotic drug, to titrate slowly, to monitor serum levels of prescribed drugs, and to keep the drug at the minimal effective dose.


Assuntos
Antipsicóticos/administração & dosagem , Epilepsia , Benzodiazepinas , Epilepsia/induzido quimicamente , Humanos , Olanzapina , Esquizofrenia
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 672-678, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762236

RESUMO

OBJECTIVE: To determine the impact olanzapine (OLA) on the hippocampal neuron of model rats with depression. METHODS: Rats were divided into five groups: control, chronic unpredicted stress (CUS), OAL (0.5, 1, 2 mg/kg), si-Atg5, and OAL (2 mg/kg)+si-Atg5. Open field and sucrose preference tests were performed to evaluate rat behaviors. Cell apoptosis was detected with Tunnel. The concentrations of interleukin (IL)-1ß and IL-18 were determined by ELISA. The expressions of cleaved Caspase-3, cleaved Caspase-9, LC3, Beclin1, P62, NLRP3 and cleaved Caspase-1 were measured by Western blot. RESULTS: OAL (0.5, 1, 2 mg/kg) increased the total moving distance, sucrose consumption and preference rate of CUS rats, and decreased serum IL-18, cell apoptosis and the expressions of cleaved Caspase-9, cleaved Caspase-1 and NLRP3 in the CA3 region of hippocampus. Although OAL (1, 2 mg/kg) decreased the expression of cleaved Caspase-3 and serum IL-1ß, OAL (0.5 mg/kg) showed no detectable effects. Si-Atg5 decreased the total moving distance, sucrose consumption and preference rate of CUS rats, enhanced the expressions of cleaved Caspase-3, cleaved Caspase-9, cleaved Caspase-1 and NLRP3, and weakened the effect of OAL (2 mg/kg). OAL (0.5, 1, 2 mg/kg) also increased the LC3Ⅱ/LC3Ⅰ ratio and the expression of Beclin1 in the CA3 region of hippocampus. OAL (1, 2 mg/kg) reduced the expression of p62, but not when it was reduced to 0.5 mg/kg. Si-Atg5 reduced the LC3Ⅱ/LC3Ⅰ ratio and the expression of Beclin1, and weakened the function of OAL (2 mg/kg). CONCLUSION: OAL can protect the hippocampal neuron of CUS rats via inhibiting NLRP3 inflammasome activation.


Assuntos
Depressão/tratamento farmacológico , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Neurônios/efeitos dos fármacos , Olanzapina/farmacologia , Animais , Hipocampo/citologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos
7.
Medicine (Baltimore) ; 98(38): e17237, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567988

RESUMO

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


Assuntos
Antipsicóticos/efeitos adversos , Eletroacupuntura , Síndrome Metabólica/terapia , Olanzapina/efeitos adversos , Risperidona/efeitos adversos , Antipsicóticos/uso terapêutico , Protocolos Clínicos , Eletroacupuntura/efeitos adversos , Eletroacupuntura/métodos , Humanos , Síndrome Metabólica/induzido quimicamente , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
8.
Actas esp. psiquiatr ; 47(5): 190-201, sept.-oct. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-185171

RESUMO

El trastorno esquizoafectivo (TEA) es un trastorno psicótico que ha entrañado cierta controversia nosológica, junto a esta dificultad encontramos muy pocos estudios que aborden su tratamiento como una entidad diferente a la esquizofrenia. Estas dos dificultades dan como resultado la falta de evidencia específica sobre el tratamiento. Actualmente, el mismo, se basa principalmente en el empleo de antipsicóticos, aunque no existen guías específicas de manejo terapéutico. Esta revisión tiene el objetivo de conocer cuáles son los fármacos que actualmente cuentan con estudios de mayor calidad científica que avalen su empleo según variables clínicas de efectividad, seguridad, adherencia y tolerancia, así como su papel en los diferentes subtipos de TEA y situaciones clínicas. Para ello, se realizó una revisión exhaustiva de estudios experimentales y observacionales que incluyeran pacientes con diagnóstico de TEA. Se concluyó que son necesarios más ensayos clínicos realizados en pacientes con diagnóstico exclusivo de TEA. La paliperidona, el único fármaco con uso autorizado en el TEA es el fármaco que cuenta con mayor cantidad y calidad de estudios que avalen su uso. Risperidona, olanzapina, aripiprazol y ziprasidona también tienen ensayos clínicos aleatorizados que apoyan su eficacia y seguridad. En pacientes refractarios, hay estudios observacionales que señalan la utilidad de la clozapina. Así mismo, hay evidencia de estudios observacionales que señalan la utilidad de litio y carbamazepina durante la fase de mantenimiento. Es necesario establecer el papel del tratamiento combinado con regula-dores del humor y/o antidepresivos


Schizoaffective disorder (SAD) is a psychotic disorder which has presented a certain nosological controversy. Apart from these difficulties, very few studies focused in SAD as a distinct condition from schizophrenia have been found. This lack of specifical studies on SAD results in a lack of specific evidence about treatment. Currently, its treatment is based mainly on the use of antipsychotics, although there are no specific treatment guidelines for SAD. The objective of this review is to establish which are the most recommended treatments according to evidence avail-able, considering clinical variables such as efficacy, safety, adherence, and tolerance as well as the role of these factors in different subtypes of SAD. This exhaustive review exam-ines experimental and observational studies involving patients with a diagnosis of SAD. It was concluded that more clinical trials performed exclusively on patients affected by SAD are needed. Paliperidone, the only drug with authorized use in SAD, is the one that has the highest quality of studies to support its use. Risperidone, olanzapine, aripiprazole and ziprasidone also have randomized clinical trials supporting their efficacy and safety. In treatment-refractory patients, there are observational studies indicating the usefulness of clozapine. Like-wise, there is evidence from observational studies showing the usefulness of lithium and carbamazepine during the treatment maintenance phase. It is necessary to establish the role of combined treatment with mood stabilizers and/or antidepressants


Assuntos
Humanos , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Psicofarmacologia , Resultado do Tratamento , Medicina Baseada em Evidências , Transtornos Psicóticos/tratamento farmacológico , Risperidona/uso terapêutico , Olanzapina/uso terapêutico , Aripiprazol/uso terapêutico , Clozapina/uso terapêutico , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico
10.
Endocr Regul ; 53(3): 165-177, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517634

RESUMO

OBJECTIVE: The aim of the present study was to demonstrate the spatial relationship between the c-Fos immunoreactive cells elicited by an acute treatment with neuroleptics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI) and enkephalinergic (ENK), substance P (SP), and tyrosine hydroxylase (TH) innervation fields in the rat septum. METHODS: Male Sprague Dawley rats received a single injection of OLA (5 mg), ARI (10 mg), AMI (20 mg), QUE (15 mg/kg/b.w.). Ninety min after antipsychotics administration, the animals were transcardially perfused with a fixative and the brains cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black endproduct. Afterwards, the sections were exposed to ENK, SP, and TH antibodies and the reaction product visualized by biotin-labeled fluorescent AlexaFluor 564 dye. The data were evaluated from the sections either simultaneously illuminated with fluorescent and transmission microscope beams or after merging the separately illuminated sections in the Adobe Photoshop 7.0 software. RESULTS: ENK, SP, and TH displayed characteristic spatial images formed by a dense accumulation of immunoreactive fibers and terminals on the both sides of the septum. A dense plexus of axons formed by ENK and SP immunopositive terminals were situated predominantly in the lateral, while TH ones more medial portion of the septum. QUE and AMI activated distinct amount of c-Fos expression in cells located within the SP-immunoreactive principal innervation field. The OLA effect on the c-Fos expression was very pronounced in the ventral TH-labeled principal innervation field including the space between the ENK field ventral portion and the dorsal margin of the accumbens nucleus shell. Generally, the occurrence of c-Fos cells in the ENK-immunoreactive principal innervation field, in comparison with the surrounding septal area, was less abundant after all of the four antipsychotics treatments. CONCLUSION: The data of the present study indicate that ENK, SP, and TH innervation fields may influence separate populations of septal cells activated by AMI, OLA, QUE, and ARI and that each of these region-differently innervated cells may be associated with the functional heterogeneity of the individual lateral septal nuclei.


Assuntos
Antipsicóticos/farmacologia , Encefalinas/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Septo do Cérebro/efeitos dos fármacos , Substância P/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Amissulprida/farmacologia , Animais , Aripiprazol/farmacologia , Imuno-Histoquímica , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Olanzapina/farmacologia , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Fumarato de Quetiapina/farmacologia , Ratos , Ratos Sprague-Dawley , Septo do Cérebro/metabolismo , Distribuição Tecidual/efeitos dos fármacos
11.
Chem Biol Interact ; 314: 108823, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563592

RESUMO

Schizophrenia cannot be treated sufficiently with existing antipsychotic drugs. Taken into account that increased Glycogen Synthase Kinase 3 Beta (GSK-3ß) activity is associated with schizophrenia pathophysiology and certain antipsychotics can be able to decrease GSK3ß activity, inhibition of GSK-3ß activity could be a novel approach for the treatment of schizophrenia. In the present study MK-801, a widely used chemical for the in vivo/in vitro modeling of schizophrenia was selected to evoke a detrimental effect on cellular survival via GSK3ß and related proteins. A limited number of studies have reported the curative effects of famotidine, an antiulcer drug, in schizophrenic patients. To the best of our knowledge, no study investigated the molecular mechanism of the beneficial effect of famotidine in the patients. A recent study based on computerized drug modeling software (docking) indicated that famotidine might inhibit the GSK3ß activity due to its chemical structure independent from histaminergic receptors. In this study, we aimed to investigate the effects of famotidine on the Akt/GSK-3ß/ß-catenin signaling pathway on SH-SY5Y neuroblastoma cells in the presence of MK-801. We investigated the effects of famotidine, olanzapine (an antipsychotic drug), and SB 415286 (specific GSK-3ß inhibitor), on the basal cellular survival and MK-801 induced neuronal death beside of Akt/GSK-3ß/ß-catenin protein and gene expressions in SH-SY5Y cells. Cell viability, protein and gene expressions were determined by the real-time cell analysis (xCELLigence) system, western blotting and real-time polymerase chain reactions (Rt-PCR), respectively. Our findings suggested that MK-801 administration decreased cell survival probably via the increasing GSK-3ß gene expression and activity in the SH-SY5Y cells. Pre-treatments with famotidine, olanzapine, and SB 415286 prevented MK-801 induced cell death via inhibitory effects on the MK-801 induced GSK-3ß activity. Overall, the present results suggest that famotidine has a neuroprotective effect against MK-801 via modulation of the Akt/GSK-3ß/ß-catenin signaling pathway, an important mechanism in schizophrenia neurobiology.


Assuntos
Maleato de Dizocilpina/farmacologia , Famotidina/farmacologia , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Aminofenóis/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Maleimidas/farmacologia , Olanzapina/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo
12.
Psychiatr Danub ; 31(Suppl 3): 543-548, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488788

RESUMO

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


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Cooperação do Paciente , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Clozapina/administração & dosagem , Clozapina/uso terapêutico , Haloperidol/administração & dosagem , Haloperidol/uso terapêutico , Humanos , Olanzapina/administração & dosagem , Olanzapina/uso terapêutico , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Fatores de Risco
13.
Bioanalysis ; 11(13): 1291-1302, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31379195

RESUMO

Aim: Olanzapine (OLZ) is the first-line, cost-effectiveness treatment for schizophrenia in China. A quantitative ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of OLZ in human plasma was developed. Results: LC separation was achieved on Waters XBrige C18 column. ESI+ was involved and multiple reaction monitoring transitions were at m/z 313.2→256.1 for OLZ and m/z 316.2→256.1 IS (d3-OLZ). The linear range was 0.1-20 ng/ml with LLOQ of 0.1 ng/ml. Accuracy and precision were within 10%. The validated method was successfully applied to a bioequivalence study of OLZ disintegrating tablets at dose of 5 mg with 100% reproducibility evaluated by incurred sample reanalysis. Conclusion: A robust validated method was developed for quantitation of OLZ in human plasma.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Olanzapina/sangue , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/normas , Meia-Vida , Hemólise , Humanos , Limite de Detecção , Olanzapina/farmacocinética , Olanzapina/normas , Controle de Qualidade , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/normas , Equivalência Terapêutica
14.
Toxicol Lett ; 316: 183-193, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31437515

RESUMO

Olanzapine, a representative of antipsychotics, is a first-line drug for treatment of schizophrenia. However, olanzapine-induced liver steatosis limits its clinical utilization. This study is to explore the mechanism of liver steatosis induced by olanzapine based on the regulation of transporters involved in uptake and oxidation of fatty acids. Our results revealed that 12-week oral administration of olanzapine increased hepatic triglyceride(TG), caused liver steatosis. Our further studies showed that the expression of fatty acid transporter 2(FATP2) and fatty acid binding protein 1(FABP1) were up-regulated in liver of female mice after 12-week olanzapine exposure, as well as in primary mouse hepatocytes treated with olanzapine. Olanzapine treatment also reduced hepatic ß-hydroxybutyrate level (indicator of fatty acid ß-oxidation), meanwhile, the L-carnitine (L-Car) concentration in liver of olanzapine group was significantly lower than that in control group. Further study demonstrated that both mRNA and protein expression of hepatic OCTN2 (carnitine/organic cation transporter 2) were obviously down-regulated in male mice after 12-week olanzapine treatment. Also, olanzapine markedly inhibited L-Car uptake in MDCK-hOCTN2 cells (1.06 µM of IC50), HepG2 cells and primary mouse hepatocytes. Supplementation of L-Car attenuated hepatic TG rise and improved simple steatosis in olanzapine treatment mice. Taken together, up-regulation of FATP2/FABP1 and down-regulation/inhibition of hepatic OCTN2 probably contribute to olanzapine-induced liver steatosis. Supplementation of L-Car is a promising strategy to attenuate olanzapine-induced simple steatosis.


Assuntos
Antipsicóticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Coenzima A Ligases/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Fígado Gorduroso/induzido quimicamente , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Olanzapina/toxicidade , Membro 5 da Família 22 de Carreadores de Soluto/antagonistas & inibidores , Adulto , Animais , Carnitina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Coenzima A Ligases/genética , Cães , Proteínas de Ligação a Ácido Graxo/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/prevenção & controle , Feminino , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Células Madin Darby de Rim Canino , Masculino , Camundongos Endogâmicos C57BL , Membro 5 da Família 22 de Carreadores de Soluto/genética , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Regulação para Cima
16.
JAMA ; 322(7): 622-631, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429896

RESUMO

Importance: Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission. Objective: To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent. Design, Setting, and Participants: Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017. Interventions: Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline. Main Outcomes and Measures: The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c). Results: Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016). Conclusions and Relevance: Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT01427608.


Assuntos
Transtornos Psicóticos Afetivos/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Olanzapina/uso terapêutico , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Antipsicóticos/efeitos adversos , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/efeitos adversos , Modelos de Riscos Proporcionais , Prevenção Secundária , Sertralina/uso terapêutico , Adulto Jovem
17.
Psiquiatr. biol. (Internet) ; 26(2): 45-51, mayo-ago. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-185028

RESUMO

La olanzapina es un antipsicótico comúnmente utilizado como tratamiento de enfermedades como la esquizofrenia y el trastorno bipolar. En ocasiones la manifestación de la enfermedad difiere entre sexos, pero poco se ha investigado sobre la influencia de esta diferencia biológica en la respuesta al tratamiento o en los efectos secundarios. En esta revisión sistemática analizamos estas diferencias de sexo en la efectividad y en los efectos adversos de la olanzapina. Aunque algunos estudios mostraron mayor efectividad en mujeres, este resultado es ambiguo al no encontrar diferencias en otros trabajos. Por otro lado, encontramos mayor tendencia de los hombres a la ganancia de peso y al parkinsonismo, mientras que más mujeres experimentaron mareos, mayor aumento del colesterol y del intervalo QT. Dado el amplio uso a nivel mundial de la olanzapina, es importante realizar futuros estudios analizando las diferencias observadas, ya que podrían ser cruciales para mejorar la calidad de vida de los pacientes


Olanzapine is an antipsychotic drug commonly used in the treatment of illnesses such as schizophrenia and bipolar disorder. Occasionally the manifestation of the illness differs between genders, but little has been investigated on the influence of this biological difference in the response to the treatment or the secondary effects. In this systematic review, an analysis is made of these gender differences on the effectiveness and adverse effects of olanzapine treatment. Although some studies showed a higher effectiveness in women, this was ambiguous due to not finding any differences in other works. On the other hand, there was a greater tendency for men to gain weight and suffer from Parkinson symptoms, while the women were more likely to suffer from dizzy spells, a greater increase in cholesterol, and in QT interval. Given the worldwide use of olanzapine, it is important that further studies should be performed to analyse these differences observed, since they could be crucial for improving the quality of life of the patients


Assuntos
Humanos , Olanzapina/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Distribuição por Sexo , Antipsicóticos/uso terapêutico , Olanzapina/efeitos adversos
18.
Psiquiatr. biol. (Internet) ; 26(2): 60-61, mayo-ago. 2019.
Artigo em Espanhol | IBECS | ID: ibc-185031

RESUMO

Introducción: Además de agranulocitosis, el tratamiento con clozapina se asocia con eosinofilia. Aunque es un efecto secundario poco conocido, tiene una incidencia similar a la primera y además es potencialmente grave, ya que puede afectar a órganos diana como el hígado. Presentación del caso: Varón con sintomatología psicótica que tras varias semanas de ingreso comienza tratamiento con clozapina por la falta de respuesta farmacológica. Coincidiendo con el inicio de la misma presenta eosinofilia junto con un aumento de las enzimas hepáticas que alcanzan niveles tóxicos, por lo que se procede a su retirada. Discusión: La eosinofilia inducida por la clozapina puede ser periférica y benigna o puede infiltrar órganos diana como el hígado, desencadenando una hepatitis potencialmente mortal. Conclusiones: A pesar de que la hepatitis secundaria al tratamiento con clozapina puede ser fulminante, los controles seriados de las enzimas hepáticas no se incluyen en el protocolo de seguimiento de dicho tratamiento


Introduction: In addition to agranulocytosis, treatment with clozapine is associated with eosinophilia. Although it is a little-known side effect, it has an incidence similar to the former, and is also potentially serious, since it can affect target organs, such as the liver. Presentation of the case: A male with psychotic symptoms, on whom, after several weeks in hospital, it was decided to start clozapine due to the lack of pharmacological response. Coinciding with starting the drug, he presented with eosinophilia, as well as increased liver enzymes that reached toxic levels. The drug was then withdrawn. Discussion: Eosinophilia induced by clozapine may be peripheral and benign, or it may infiltrate target organs such as the liver, triggering potentially life-threatening hepatitis. Conclusions: Although hepatitis secondary to treatment with clozapine may be fulminant, serial liver enzyme tests are not included in the follow-up protocol for this treatment


Assuntos
Humanos , Masculino , Eosinofilia/induzido quimicamente , Clozapina/efeitos adversos , Transtornos Psicóticos/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/complicações , Olanzapina/uso terapêutico , Substituição de Medicamentos/métodos , Testes de Função Hepática/estatística & dados numéricos , Ensaios Enzimáticos/métodos
20.
EBioMedicine ; 46: 248-255, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31307956

RESUMO

BACKGROUND: Antipsychotic medications are the common treatment for schizophrenia. However, reliable biomarkers that can predict individual treatment response are still lacking. The present study aimed to examine whether baseline putamen activity can predict individual treatment response in schizophrenia. METHODS: Two independent samples of patients with drug-naive, first-episode schizophrenia (32 patients in sample 1 and 44 in sample 2) and matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) at baseline. Patients were treated with olanzapine for 8 weeks; symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and week 8. Fractional amplitude of low frequency fluctuation (fALFF) and pattern classification techniques were used to analyze the data. FINDINGS: Univariate analysis shows an elevated pre-treatment fALFF in the left ventromedial putamen in both patient samples compared to healthy controls (p's < 0.001). The support vector regression (SVR) analysis suggests a positive relationship between baseline pre-treatment fALFF in the left ventromedial putamen and improvement in positive symptom at week 8 in each patient group using a cross-validated method (r = 0.452, p = .002; r = 0.511, p = .003, respectively). INTERPRETATION: Our study suggests that elevated pre-treatment mean fALFF in the left ventromedial putamen may predict individual therapeutic response to olanzapine treatment in drug-naive, first-episode patients with schizophrenia. Future studies are needed to confirm whether this finding is generalizable to patients with schizophrenia treated with other antipsychotic medications. FUND: The National Key R&D Program of China and the National Natural Science Foundation of China.


Assuntos
Imagem por Ressonância Magnética , Putamen/diagnóstico por imagem , Putamen/fisiopatologia , Esquizofrenia/diagnóstico , Adolescente , Adulto , Estudos de Casos e Controles , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Olanzapina/metabolismo , Prognóstico , Esquizofrenia/tratamento farmacológico , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA