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1.
Drug Des Devel Ther ; 12: 711-719, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670329

RESUMO

BACKGROUND: Norquetiapine (N-desalkyl quetiapine, NQ) is an active metabolite of quetiapine with stable pharmacokinetic and pharmacological properties. However, its short half-life is a drawback for clinical applications, and long-acting formulations are required. PURPOSE: The objectives of this study were to prepare improved entrapment efficiency NQ freebase microspheres by the solvent evaporation method with poly(d,l-lactic-co-glycolic acid) (PLGA) as a release modulator and to evaluate their physicochemical and in vitro/in vivo release properties. METHODS: NQ freebase PLGA (1:5 w/w) formulations were prepared by the oil-in-water (o/w) emulsion-solvent evaporation method. A solution of the drug and PLGA in 9:1 v/v dichloromethane:ethanol was mixed with 0.2% polyvinyl alcohol and homogenized at 2,800 rpm. The emulsion was stirred for 3 h to dilute and evaporate the solvent. After that, the resulting product was freeze-dried. Drug-loading capacity was measured by the validated RP-HPLC method. The surface morphology of the microspheres was observed by scanning electron microscopy (SEM), and the physicochemical properties were evaluated by differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy particle size distribution. The in vitro dissolution test was performed using a rotary shaking bath at 37°C, with constant shaking at 50 rpm in sink condition. RESULTS: The NQ freebase microspheres prepared by o/w emulsion-solvent evaporation showed over 30% efficiency. NQ was confirmed to be amorphous in the microspheres by powder X-ray diffraction and differential scanning calorimetry. Special chemical interaction in the microspheres was not observed by FT-IR. The in vitro dissolution test demonstrated that the prepared microspheres' release properties were maintained for more than 20 days. The in vivo test also confirmed that the particles' long acting properties were maintained. Therefore, good in vitro-in vivo correlation was established. CONCLUSION: In this study, NQ freebase-PLGA microspheres showed potential for the treatment of schizophrenia for long-periods.


Assuntos
Dibenzotiazepinas/farmacocinética , Ácido Láctico/farmacocinética , Microesferas , Ácido Poliglicólico/farmacocinética , Animais , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/química , Ácido Láctico/administração & dosagem , Ácido Láctico/química , Tamanho da Partícula , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
3.
Chem Pharm Bull (Tokyo) ; 64(11): 1546-1554, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27803466

RESUMO

Quetiapine (QTP) is an atypical antipsychotic drug commonly used to treat several psychiatric disorders and is metabolized into the active metabolite norquetiapine (NQTP). This study was designed to evaluate and compare the physicochemical properties, metabolic stability, brain distribution, and pharmacokinetics of QTP and NQTP. Compared to QTP, NQTP had a higher pKa, solubility, and rat liver microsomal stability, optimal log D and similar log P values. For pharmacokinetic evaluation, QTP and NQTP were administered orally and intravenously to rats at various doses. The plasma QTP and NQTP concentrations in rats were determined by a fully-validated liquid-chromatography tandem mass spectrometry (LC-MS/MS). Over the investigated dosing range, both QTP and NQTP showed linear pharmacokinetics. Following oral administration of the same dose, the area under the concentration-time curve (AUC0-∞) and maximum serum concentration (Cmax) were larger after NQTP administration compared to QTP administration. In addition, NQTP had a greater absolute oral bioavailability compared to QTP (15.6% vs. 0.63%, respectively). The brain-to-plasma concentration ratio was greater after NQTP administration compared to the QTP and NQTP ratios after QTP administration. NQTP administration results in increased systemic exposure and brain distribution compared to QTP administration. Future studies are needed to evaluate the pharmacologic and toxicologic effects of increased NQTP exposures.


Assuntos
Encéfalo/metabolismo , Dibenzotiazepinas/metabolismo , Dibenzotiazepinas/farmacocinética , Microssomos Hepáticos/metabolismo , Fumarato de Quetiapina/metabolismo , Fumarato de Quetiapina/farmacocinética , Administração Oral , Animais , Físico-Química , Dibenzotiazepinas/administração & dosagem , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Masculino , Microssomos Hepáticos/química , Fumarato de Quetiapina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Solubilidade , Distribuição Tecidual
4.
Artigo em Russo | MEDLINE | ID: mdl-26356516

RESUMO

AIM: To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics. MATERIAL AND METHODS: A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMI<30 kg/m²) and obesity grade 2-3 in 38 patients (BMI>30 kg/m²). RESULTS AND CONCLUSION: Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these RESULTS: we developed recommendations for management of patients treated with second generation antipsychotics.


Assuntos
Antipsicóticos/efeitos adversos , Dibenzotiazepinas/efeitos adversos , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos Psicóticos/tratamento farmacológico , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Dibenzotiazepinas/administração & dosagem , Transtornos da Alimentação e da Ingestão de Alimentos/induzido quimicamente , Feminino , Humanos , Masculino , Obesidade/induzido quimicamente , Obesidade/epidemiologia , Olanzapina , Transtornos Psicóticos/epidemiologia , Fumarato de Quetiapina , Risperidona/uso terapêutico , Esquizofrenia/epidemiologia , Adulto Jovem
5.
Glob J Health Sci ; 7(5): 359-63, 2015 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-26156901

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of Quetiapine versus Risperidone in control of acute psychotic signs and symptoms in hospitalized patients during four weeks. METHODS: In this double-blind, randomized controlled study, a total of 90 patients with a confirmed diagnosis acute psychosis and were hospitalized in Zare Hospital, Sari, Iran, and they were treated with Quetiapine (mean 500 mg/day) or Risperidone (mean 5.2 mg/day), in a 4 week period. The positive and negative symptoms scale (PANSS) and Clinical Global Impression-Severity scale (CGI-s) were used to assess psychotic symptoms and severity of illness in first and the last day of the study. RESULTS: No significant difference found between two groups in decreasing positive and negative sub-scores in the PANSS. Risperidone was superior to Quetiapine in decreasing the PANSS general psychopathology sub-scores and total score (p<0.05). No significant difference found between two groups in decreasing CGI-s score.


Assuntos
Antipsicóticos/administração & dosagem , Dibenzotiazepinas/administração & dosagem , Transtornos Psicóticos/tratamento farmacológico , Risperidona/administração & dosagem , Doença Aguda , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fumarato de Quetiapina , Índice de Gravidade de Doença , Adulto Jovem
6.
Psychiatr Pol ; 49(1): 81-93, 2015.
Artigo em Polonês | MEDLINE | ID: mdl-25844412

RESUMO

Quetiapine is an atypical antipsychotic agent, frequently used in psychiatry, often for symptomatic treatment against a number of mental disorders differing from the registration indications. One of the use is to soothe the clinical conditions caused by the use of various psychoactive substances. The paper presents and discusses the reports of quetiapine misuse, abuse, and even mental addiction, as well as symptoms similar to the so-called discontinuation syndrome, often mixed with withdrawal syndrome occurring in the course of addiction. Most reports concern males, and especially those with a history of other psychoactive substance abuse, and personality disorders, often in conflict with the law. Therefore, clinicians should be cautious when prescribing quetiapine to such patients. The article discusses potential mechanisms responsible for quetiapine abuse. This is probably related to its sedative and anxiolytic activity which results in the frequent use with stimulants. Also, high affinity for the H1 receptor, as antihistamines agents causes rewarding action.


Assuntos
Antipsicóticos/efeitos adversos , Dibenzotiazepinas/efeitos adversos , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Síndrome de Abstinência a Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/etiologia , Antipsicóticos/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Dibenzotiazepinas/administração & dosagem , Humanos , Fumarato de Quetiapina , Esquizofrenia/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
7.
Psychiatr Pol ; 49(1): 67-80, 2015.
Artigo em Polonês | MEDLINE | ID: mdl-25844411

RESUMO

This article presents a summary of available data on the use of quetiapine extended release (QUE-XR). QUE-XR is an example of an atypical antipsychotic drug that can be used in a single dose, thereby simplifying the treatment regimen. From the therapeutic standpoint, this issue is of paramount importance, since approximately 50% of patients have adherence issues. Therefore, availability of the drug which is comfortable in administration can significantly improve treatment outcomes. Due to its antipsychotic, antidepressive, mood stabilizing and anxiolytic efficacy, QUE-XR seems to be a promising drug with potentially broad spectrum of indications (in patients with schizophrenia, bipolar disorder, major depression and some anxiety disorders - both in the acute phase of treatment, and the maintenance treatment). Notably, QUE-XR seems to ameliorate sleep disturbances, and it may also improve patients' quality of life (as suggested by some studies). Due to the simple dosing regimen of QUE-XR, conducting therapy with this drug may contribute to the improvement of compliance. Yet, the primary clinical criterion for selection of the type of formulation of quetiapine should be the individual preferences of the patient, and the knowledge and experience of the treating physician.


Assuntos
Antipsicóticos/administração & dosagem , Dibenzotiazepinas/administração & dosagem , Transtornos Mentais/tratamento farmacológico , Administração Oral , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Preparações de Ação Retardada , Transtorno Depressivo Maior/tratamento farmacológico , Relação Dose-Resposta a Droga , Humanos , Qualidade de Vida , Fumarato de Quetiapina , Esquizofrenia/tratamento farmacológico
8.
Breast Cancer Res Treat ; 149(3): 705-14, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25667102

RESUMO

Bone loss is one of the major complications of advanced cancers such as breast cancer, prostate cancer, and lung cancer. Extensive research has revealed that the receptor activator of NF-κB ligand (RANKL), which is considered to be a key factor in osteoclast differentiation, plays an important role in cancer-associated bone resorption. Therefore, agents that can suppress this bone loss have therapeutic potential. In this study, we detected whether quetiapine (QUE), a commonly used atypical antipsychotic drug, can inhibit RANKL-induced osteoclast differentiation in vitro and prevent human breast cancer-induced bone loss in vivo. RAW 264.7 cells and bone marrow-derived macrophages (BMMs) were used to detect inhibitory effect of QUE on osteoclastogenesis in vitro. Mouse model of breast cancer metastasis to bone was used to test suppressive effect of QUE on breast cancer-induced bone loss in vivo. Our results show that QUE can inhibit RANKL-induced osteoclast differentiation from RAW 264.7 cells and BMMs without signs of cytotoxicity. Moreover, QUE reduced the occurrence of MDA-MB-231 cell-induced osteolytic bone loss by suppressing the differentiation of osteoclasts. Finally, molecular analysis revealed that it is by inhibiting RANKL-mediated MAPK and NF-κB signaling pathways that QUE suppressed the osteoclast differentiation. We demonstrate, for the first time, the novel suppressive effects of QUE on RANKL-induced osteoclast differentiation in vitro and human breast cancer-induced bone loss in vivo, suggesting that QUE may be a potential therapeutic drug for osteolysis treatment.


Assuntos
Reabsorção Óssea/genética , Neoplasias da Mama/tratamento farmacológico , Dibenzotiazepinas/administração & dosagem , Ligante RANK/genética , Animais , Reabsorção Óssea/complicações , Reabsorção Óssea/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos , NF-kappa B/genética , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Fumarato de Quetiapina , Ligante RANK/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
9.
Paediatr Drugs ; 17(2): 125-40, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25686575

RESUMO

The atypical antipsychotic quetiapine has been used in different psychotic and non-psychotic disorders in children and adolescents in randomized clinical trials, open-label studies and chart reviews. Most of these studies suggest that quetiapine may be a promising agent with a potential for use in young patients. The aim of this paper is to critically review available literature on quetiapine in the treatment of children and adolescents with a variety of psychiatric disorders, including psychotic disorders, bipolar disorders (manic and depressive episodes), conduct disorder, autism spectrum disorder, Tourette's syndrome and personality disorders. Furthermore, we report on possible neurochemical pathways involved during treatment with quetiapine, and discuss some issues that are clinically relevant in daily practice, such as titration strategies, safety and tolerability, and monitoring possible side effects. Controlled studies support the short-term efficacy for treating psychosis, mania, and aggression within certain diagnostic categories. However, although quetiapine seems well tolerated in various pediatric populations during acute and intermediate treatments, and hyper-prolactinemia and extra-pyramidal side effects are consistently low among studies, weight gain and alterations in lipid profile need to be closely monitored. Furthermore, the distal benefit/risk ratio during long-term treatment remains to be determined.


Assuntos
Antipsicóticos/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Adolescente , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Criança , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/efeitos adversos , Humanos , Fumarato de Quetiapina , Aumento de Peso/efeitos dos fármacos
10.
J Am Board Fam Med ; 28(1): 154-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25567837

RESUMO

Bipolar disorder is a mental illness with a lifetime prevalence of 2% and has a dramatic impact on quality of life. Mania is a distinct period of abnormal and sustained elevated, expansive, or irritable mood and increase in goal-directed activity or energy that lasts at least 1 week and is present for most of each day. Quetiapine is an atypical antipsychotic approved for the treatment of bipolar depression and mania. For the treatment of acute mania, a dose of 600 to 800 mg/day is recommended. There has been concern of potential induction or worsening of hypomanic or manic symptoms at low doses via the ratio of 5HT2A/D2 receptor antagonism, which at lower doses favors greater 5HT2A receptor blockade and thus increases dopamine concentrations. This article describes a case report of hypomania worsening to mania with psychotic features in a drug-naïve patient who was started on low-dose quetiapine. This case adds to the existing literature of case reports indicating that low-dose quetiapine may be associated with induction or worsening of hypomanic/manic symptoms, while acknowledging the difficulty of suggesting a causal relationship.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/efeitos adversos , Adulto , Homicídio , Humanos , Masculino , Fumarato de Quetiapina
11.
Int Clin Psychopharmacol ; 30(1): 14-22, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25356632

RESUMO

The present analysis assessed the efficacy of extended-release quetiapine fumarate (quetiapine XR) versus risperidone in patients with schizophrenia and depressive symptoms [Hamilton Depression Rating Scale (HAM-D) score≥20 and a HAM-D item 1 score≥2]. This was a subanalysis of patients with schizophrenia from a randomized, open-label, parallel-group, flexible-dose study (NCT00640562) that also enrolled patients with schizoaffective disorder. The primary endpoint of this noninferiority study was change from baseline to week 12 in Calgary Depression Scale for Schizophrenia score (per protocol population). Overall, 114 patients received quetiapine XR (n=60; 400-800 mg/day) or risperidone (n=54; 4-6 mg/day). Change in Calgary Depression Scale for Schizophrenia score was greater for quetiapine XR than for risperidone [least squares means: -7.2 vs. -4.8; treatment difference 2.4 (95% confidence interval 0.3-4.6; P<0.05)]. Adverse events (≥3%) among patients receiving quetiapine XR were sedation, somnolence, and dry mouth, and among those receiving risperidone were anxiety, insomnia, asthenia, hyperprolactinemia, and somnolence. Abnormally high prolactin levels were reported for 57.6 and 8.1% of patients receiving risperidone and quetiapine XR, respectively. Quetiapine XR was superior to risperidone at reducing depressive symptoms in patients with schizophrenia.


Assuntos
Antipsicóticos/administração & dosagem , Depressão/tratamento farmacológico , Dibenzotiazepinas/administração & dosagem , Risperidona/administração & dosagem , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Antipsicóticos/efeitos adversos , Preparações de Ação Retardada , Depressão/diagnóstico , Depressão/psicologia , Dibenzotiazepinas/efeitos adversos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fumarato de Quetiapina , Risperidona/efeitos adversos , Esquizofrenia/diagnóstico , Fatores de Tempo , Resultado do Tratamento
12.
Int Clin Psychopharmacol ; 30(1): 54-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25371174

RESUMO

This study investigated the dosing patterns of quetiapine augmentation (QA) for major depressive disorder (MDD) in routine practice. Between 1 January 2009 and 31 May 2013, patients with a diagnosis of MDD who were receiving QA in conjunction with an ongoing antidepressant were recruited into this study. The electronic medical records and clinical data for a total of 977 patients were reviewed up to a year. Almost half the patients maintained QA treatment for more than 3 months. The mean duration of QA was ∼6 months, and the mean initial and maintenance doses were 23.6 and 40.7 mg/day, respectively (range=12.5-400 mg/day). The most frequent adverse events observed were somnolence, followed by dry mouth and lethargy. Our results indicate that the actual doses of QA for MDD in routine practice should be lower than the doses used in placebo-controlled clinical trials and those recommended by a regulatory agency. Adequately powered and well-controlled prospective studies are needed to better understand the exact role of low doses of QA in the treatment of MDD, particularly in routine practice.


Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Dibenzotiazepinas/administração & dosagem , Padrões de Prática Médica , Adulto , Idoso , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Dibenzotiazepinas/efeitos adversos , Cálculos da Dosagem de Medicamento , Quimioterapia Combinada , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Fumarato de Quetiapina , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
13.
J Am Acad Child Adolesc Psychiatry ; 53(11): 1179-90,1190.e1-4, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25440308

RESUMO

OBJECTIVE: To assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths. METHOD: This study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (mean = 14.6 ± 2.9 years). Of those, 248 (88.8%) received a single antipsychotic (risperidone, olanzapine, or quetiapine) and completed 2 visits, and 178 (63.8%) completed the 6-month follow-up. Patients had schizophrenia-spectrum disorders (44.5%), mood-spectrum disorders (23.2%), disruptive behavioral disorders (17.3%), or other disorders (15.1%). Fifteen age- and gender-matched, healthy, nonmedicated individuals served as a comparison group. RESULTS: From baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (n = 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (n = 44; 11.5 kg and 1.08 BMI z score), and quetiapine (n = 47; 6.3 kg and 0.54 BMI z score), but not in healthy control participants (-0.11 kg and 0.006 BMI z score). Fasting metabolic parameters increased significantly with risperidone (glucose [3.8] mg/dL, insulin [4.9] mU/L, homeostasis model assessment of insulin resistance [HOMA-IR: 1.2], triglycerides [15.6] mg/dL), and olanzapine (glucose [5.0] mg/dL, total cholesterol [21.2] mg/dL, and low-density lipoprotein cholesterol [44.6] mg/dL), but not with quetiapine or in healthy control participants. The percentage of research participants considered to be "at risk of adverse health outcome" increased during the 6 months from 8.9% to 29.2% for risperidone (p < .0001), 6.8% to 38.1% for olanzapine (p < .0001), and 6.3% to 4.0% for quetiapine (p = .91). CONCLUSION: Olanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporal side effect patterns.


Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Adolescente , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/uso terapêutico , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Olanzapina , Prognóstico , Estudos Prospectivos , Fumarato de Quetiapina , Fatores de Risco , Risperidona/efeitos adversos , Risperidona/uso terapêutico
14.
J Clin Psychiatry ; 75(10): e26, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25373131

RESUMO

Patients with bipolar disorder spend more time depressed than manic, but fewer clinical trials have been conducted investigating treatments for bipolar depression than for bipolar mania. Olanzapine-fluoxetine combination, quetiapine, and lurasidone are the only FDA-approved treatments for bipolar depression. Clinical trials of these drugs show similar efficacy but different side effect profiles. Clinicians, therefore, should consider possible adverse events and individual patient characteristics when selecting treatments.


Assuntos
Antidepressivos de Segunda Geração/farmacologia , Antipsicóticos/farmacologia , Benzodiazepinas/farmacologia , Transtorno Bipolar/tratamento farmacológico , Dibenzotiazepinas/farmacologia , Fluoxetina/farmacologia , Isoindóis/farmacologia , Tiazóis/farmacologia , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos de Segunda Geração/efeitos adversos , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/efeitos adversos , Combinação de Medicamentos , Fluoxetina/administração & dosagem , Fluoxetina/efeitos adversos , Humanos , Isoindóis/administração & dosagem , Isoindóis/efeitos adversos , Cloridrato de Lurasidona , Fumarato de Quetiapina , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos
15.
J Integr Neurosci ; 13(4): 669-92, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25391717

RESUMO

Stress is any condition that seriously affects the balance of the organism physiologically and psychologically. Stress activates the hypothalamic-pituitary-adrenal (HPA) releasing glucocorticoid hormones that produce generalized effects on different body systems including the nervous system. This study aimed to investigate the effect of acute restraint stress (ARS) on cognitive performance by measuring spatial working memory in Y-maze, behavior (anxiety and exploratory behavior) in open field test, expression of synaptophysin and glial fibrillary acidic protein (GFAP) in the hippocampus by immunohistochemistry, dopaminergic receptors (D2) in the basal ganglia by gene expression and comparing the effect of ghrelin and quetiapine on the previous parameters. 36 adult male albino rats constituted the animal model of this work and have been divided into six groups: control group, control group exposed to ARS, quetiapine group, quetiapine group exposed to ARS, ghrelin group and ghrelin group exposed to ARS. We demonstrated more neuroprotective effect for quetiapine compared to ghrelin on stress response, anxiety behavior and working spatial memory impairment due to ARS.


Assuntos
Antipsicóticos/administração & dosagem , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Dibenzotiazepinas/administração & dosagem , Grelina/administração & dosagem , Estresse Psicológico/complicações , Análise de Variância , Animais , Transtornos Cognitivos/sangue , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Comportamento Exploratório/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Hidrocortisona/sangue , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Fumarato de Quetiapina , Ratos , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Estresse Psicológico/sangue
16.
J Clin Psychiatry ; 75(9): e924-31, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25295435

RESUMO

OBJECTIVE: Previous studies suggested that antidepressants augmented with second-generation antipsychotics (SGAs), including aripiprazole, olanzapine, quetiapine, and risperidone, resulted in better treatment response or higher rates of remission in patients with major depressive disorder (MDD). However, population-based study on SGA augmentation for patients with MDD remains limited. The purpose of this study was to investigate the effectiveness of SGA augmentation for treatment of MDD using the National Health Insurance Research Database in Taiwan. METHOD: The subjects were patients with MDD (ICD-9-CM code: 296.2 and 296.3) who were initially admitted to psychiatric inpatient settings for the first time between January 1, 1996, and December 31, 2007, and could be tracked until December 31, 2011. To assess the treatment effect of SGA augmentation, 993 MDD patients who received aripiprazole, olanzapine, quetiapine, or risperidone augmentation treatment for 8 weeks or more were included in this 1-year mirror-image study. Outcome measures included length of psychiatric hospitalization and number of psychiatric admissions and emergency room (ER) visits. RESULTS: After patients received SGA augmentation treatment, key psychiatric service use (including length of psychiatric hospitalization [P < .0001], number of psychiatric admissions [P < .0001], and ER visits [P = .0006]) due to MDD diagnosis was significantly reduced. Subgrouping analysis for each SGA drug also showed significant reduction in number of psychiatric admissions for MDD patients who received aripiprazole (P < .0001), olanzapine (P = .003), quetiapine (P < .0001), and risperidone (P < .0001). CONCLUSIONS: The study provides support that aripiprazole, olanzapine, quetiapine, and risperidone augmentation therapy could be effective in reducing psychiatric service utilization among MDD patients.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Dibenzotiazepinas/uso terapêutico , Piperazinas/uso terapêutico , Quinolonas/uso terapêutico , Risperidona/uso terapêutico , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Antipsicóticos/administração & dosagem , Aripiprazol , Dibenzotiazepinas/administração & dosagem , Sinergismo Farmacológico , Quimioterapia Combinada , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Piperazinas/administração & dosagem , Fumarato de Quetiapina , Quinolonas/administração & dosagem , Risperidona/administração & dosagem , Taiwan/epidemiologia , Resultado do Tratamento
17.
BMC Psychiatry ; 14: 246, 2014 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-25174996

RESUMO

BACKGROUND: Bipolar manic episodes often require hospital admission to ensure patient safety. The antipsychotic quetiapine is a common treatment for bipolar mania and is available in immediate release (IR) and extended release (XR) formulations; however, outcomes in patients receiving these different formulations have not been directly compared in an acute hospital setting. METHODS: We conducted a multinational, observational, retrospective cohort study to describe and compare hospital stay in patients admitted for an acute bipolar manic episode treated with quetiapine IR or XR from 1 October 2009-1 October 2010. The primary outcome measure was comparison of length of stay (LOS) using zero-truncated negative binomial regression. RESULTS: In total, 1230 patients were included (659 in the IR cohort; 571 in the XR cohort). The median LOS (interquartile range) was 18.0 days (12.0, 28.0) in the IR cohort and 20.0 days (12.0, 34.0) in the XR cohort, respectively. LOS was not significantly associated with quetiapine formulation irrespective of whether or not clinical characteristics were taken into account (p = 0.820 and p = 0.386, respectively). Overall, 84.2% and 84.4% of patients in the IR and XR cohorts, respectively, had not previously used quetiapine; of these patients, 78.7% and 68.9% received one total daily dose, and 14.4% and 23.9% received dose titration. Over half of patients received antipsychotic monotherapy (53.1% and 58.3% in the IR and XR cohorts, respectively) and most received a daily quetiapine dose ≥ 400 mg (64.9% and 71.8%, respectively, for quetiapine monotherapy and 59.9% and 80.3%, respectively, for combination treatment). As a secondary outcome, multivariate analysis was used to identify other factors that affect LOS. Factors associated with a longer hospital stay included public funding versus private, maximum number of new medications administered, did not receive lithium and did not receive anxiolytics, sedatives/hypnotics (all p < 0.0001). Factors associated with a shorter hospital stay included presence of drug/alcohol abuse, living accompanied and having a psychiatric medical history (all p < 0.05). CONCLUSIONS: LOS was not found to be associated with quetiapine formulation. However, most patients received only one total daily dose of quetiapine without dose titration, which was unexpected and contrary to current recommendations. TRIAL REGISTRATION: NCT01239589.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Preparações de Ação Retardada/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Tempo de Internação , Adulto , Antipsicóticos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Dibenzotiazepinas/administração & dosagem , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Fumarato de Quetiapina , Estudos Retrospectivos , Resultado do Tratamento
18.
Expert Rev Neurother ; 14(9): 987-1005, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25096854

RESUMO

Management of bipolar disorder (BD) requires a complex combination of pharmacological and psychosocial interventions. Over recent decades the therapeutic arsenal for BD has expanded to include lithium, anticonvulsants and second-generation antipsychotics (SGAs). Immediate release (IR) quetiapine fumarate is a SGA approved in several countries for the treatment of patients with schizophrenia and BD or as an add-on treatment for major depressive disorders. Extended release (XR) quetiapine fumarate was developed more recently. There is interest in a once-daily formulation which may improve patient compliance but there may be some differences between quetiapine IR and XR in terms of safety and efficacy. This article provides an update of recent data on the efficacy and safety of quetiapine XR for the treatment of BD.


Assuntos
Antipsicóticos/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Dibenzotiazepinas/administração & dosagem , Sistemas de Liberação de Medicamentos , Antipsicóticos/farmacologia , Bases de Dados Factuais/estatística & dados numéricos , Dibenzotiazepinas/farmacologia , Humanos , Fumarato de Quetiapina
19.
Alcohol Clin Exp Res ; 38(7): 2113-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24976394

RESUMO

BACKGROUND: Alcohol dependence is common in bipolar disorder (BPD) and associated with treatment nonadherence, violence, and hospitalization. Quetiapine is a standard treatment for BPD. We previously reported improvement in depressive symptoms, but not alcohol use, with quetiapine in BPD and alcohol dependence. However, mean alcohol use was low and a larger effect size on alcohol-related measures was observed in those with higher levels of alcohol consumption. In this study, efficacy of quetiapine in patients with BPD and alcohol dependence was examined in patients with higher mean baseline alcohol use than in the prior study. METHODS: Ninety outpatients with bipolar I or II disorders, depressed or mixed mood state, and current alcohol dependence were randomized to 12 weeks of sustained release quetiapine (to 600 mg/d) add-on therapy or placebo. Drinking was quantified using the Timeline Follow Back method. Additional assessment tools included the Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, Penn Alcohol Craving Scale, liver enzymes, and side effects. Alcohol use and mood were analyzed using a declining-effects random-regression model. RESULTS: Baseline and demographic characteristics in the 2 groups were similar. No significant between-group differences were observed on the primary outcome measure of drinks per day or other alcohol-related or mood measures (p > 0.05). Overall side effect burden, glucose, and cholesterol were similar in the 2 groups. However, a significant weight increase was observed with quetiapine at week 6 (+2.9 lbs [SE 1.4] quetiapine vs. -2.0 lbs [SE 1.4], p = 0.03), but not at week 12. Scores on the Barnes Akathisia Scale increased significantly more (p = 0.04) with quetiapine (+0.40 [SE 0.3]) than placebo (-0.52 [SE 0.3]) at week 6 but not week 12. Retention (survival) in the study was similar in the groups. CONCLUSIONS: Findings suggest that quetiapine does not reduce alcohol consumption in patients with BPD and alcohol dependence.


Assuntos
Alcoolismo/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Dibenzotiazepinas/uso terapêutico , Adulto , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/complicações , Alcoolismo/psicologia , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Transtorno Bipolar/complicações , Fissura/efeitos dos fármacos , Preparações de Ação Retardada/uso terapêutico , Diagnóstico Duplo (Psiquiatria) , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Fumarato de Quetiapina , Resultado do Tratamento , Adulto Jovem
20.
J Clin Psychiatry ; 75(10): 1062-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25007003

RESUMO

OBJECTIVE: To study the efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar I or II depression with comorbid generalized anxiety disorder (GAD) and other comorbidities. METHOD: The study was conducted from January 2007 to November 2011. The Mini-International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV bipolar disorder, GAD, and other Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. The Hamilton Depression Rating Scale-17 items (HDRS-17) was used as a primary outcome to evaluate the difference between the 2 groups using the change from baseline to end of study. Last observation carried forward and mixed-effects modeling for repeated measures were used to analyze the primary and secondary outcome measures. RESULTS: Of the 120 patients screened, 100 patients were randomized to receive quetiapine-XR (n = 50) or placebo (n = 50). Twenty-six patients in the quetiapine-XR and 18 in the placebo group completed the study. The mean quetiapine-XR dose was 276 ± 50 mg/d (50-300 mg/d). There was no significant difference between the 2 groups in the change from baseline to end of study in HDRS-17 total score with an effect size of 0.19 favoring quetiapine-XR. There were also no significant differences between the 2 groups in secondary efficacy and safety outcome measures. CONCLUSIONS: Quetiapine-XR was not significantly superior to placebo in bipolar I or II depression with GAD and other comorbidities, suggesting that data from relatively "pure" bipolar patients may not be generalizable to a highly comorbid population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00671853.


Assuntos
Antipsicóticos/farmacologia , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Dibenzotiazepinas/farmacologia , Doença Aguda , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/epidemiologia , Comorbidade , Preparações de Ação Retardada , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/efeitos adversos , Método Duplo-Cego , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Fumarato de Quetiapina , Resultado do Tratamento
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