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1.
Medicine (Baltimore) ; 100(3): e23958, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545976

RESUMO

BACKGROUND: Pediatric obstructive sleep apnea syndrome (OSAS) is significant public concern. Clinical practice indicates that montelukast has certain therapeutic advantages, while there is a lack of evidence-based medicine support. The aim of this study is to synthesize related data to explore efficacy and safety of montelukast for pediatric OSAS. METHODS: Data in Pubmed, EMBASE, CENTRAL, CBM, CNKI, WanFang, VIP databases were comprehensively searched. All the randomized controlled trials (RCTs) in OSAS children were identified, in which the effects of montelukast on a range of outcomes were compared. The search had a deadline of January 1, 2020. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literature. RESULTS: The efficacy and safety of montelukast in the treatment of pediatric OSAS were evaluated in terms of apnea hypopnea index (AHI), the Pittsburgh Sleep Quality Index, the Epworth Sleep Scale (ESS), neck circumference, important index in Polysomnography: sleep efficiency, desaturation index, total sleep time. CONCLUSIONS: This study provides reliable evidence-based support for the clinical application of montelukast in the treatment of pediatric OSAS. PROSPERO REGISTRATION NUMBER: CRD42020146940.


Assuntos
Acetatos/uso terapêutico , Protocolos Clínicos , Ciclopropanos/uso terapêutico , Quinolinas/uso terapêutico , Apneia Obstrutiva do Sono/tratamento farmacológico , Sulfetos/uso terapêutico , Acetatos/efeitos adversos , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Criança , Ciclopropanos/efeitos adversos , Humanos , Metanálise como Assunto , Polissonografia/métodos , Quinolinas/efeitos adversos , Apneia Obstrutiva do Sono/fisiopatologia , Sulfetos/efeitos adversos , Revisões Sistemáticas como Assunto
2.
Medicine (Baltimore) ; 99(52): e23453, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350727

RESUMO

BACKGROUND: Bronchial asthma (BA) is a chronic airway inflammatory disease with reversible airflow limitation as the main clinical manifestations, such as wheezing, cough, shortness of breath, chest tightness, etc, mediated by a variety of inflammatory cells, which can be recurrent. Clinical can improve symptoms, but cannot be cured; glucocorticoid is the most important first-line medication. Clinical practice has shown that montelukast sodium combined with fluticasone in the treatment of adult BA can improve clinical efficacy and reduce adverse reactions. The purpose of this study is to systematically study the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult BA. METHODS: The Chinese databases (CNKI, VIP, Wanfang, Chinese Biomedical Database) and English databases (PubMed, the Cochrane Library, Embase, Web of Science) were searched by computer, for the randomized controlled clinical studies of montelukast sodium combined with fluticasone in the treatment of adult BA from establishment of database to October 2020. Two researchers independently extracted the relevant data and evaluated the quality of the literatures, and used RevMan5.3 software to conduct meta-analyze of the included literatures. RESULTS: This study assessed the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult BA through total effective rate, pulmonary function (FEV1, FVC, PEF, FEV1/FVC), and adverse reactions. CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of montelukast sodium combined with fluticasone in the treatment of adult BA. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/CKQFM.


Assuntos
Acetatos/administração & dosagem , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Ciclopropanos/administração & dosagem , Fluticasona/administração & dosagem , Metanálise como Assunto , Quinolinas/administração & dosagem , Projetos de Pesquisa , Sulfetos/administração & dosagem , Revisões Sistemáticas como Assunto/métodos , Acetatos/efeitos adversos , Adulto , Antiasmáticos/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Ciclopropanos/efeitos adversos , Combinação de Medicamentos , Fluticasona/efeitos adversos , Humanos , Quinolinas/efeitos adversos , Sulfetos/efeitos adversos , Resultado do Tratamento
3.
Chin J Nat Med ; 18(2): 138-147, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32172949

RESUMO

Glycyrrhetinic acid (GA) is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma. Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity. However, the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated. In the study, mice were divided into control, GA-control, realgar, and co-treated groups. Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method. The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar. Some metabolites, such as phenylalanine, pyroglutamic acid (PGA), proline, carnitine, nicotinamide, choline, lysophosphatidylcholine (LPC) 16 : 0 and LPC 18 : 2 were found responsible for the hepatoprotective effect of GA. These metabolites are associated with the methylation metabolism of arsenic, cell membrane structure, energy metabolism and oxidative stress. From the results of this study, we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver, promoting the conjugation of arsenic and GSH to play detoxification effect, and ameliorating the liver metabolic perturbations caused by realgar.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Ácido Glicirretínico/farmacologia , Metabolômica , Animais , Arsenicais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Cromatografia Líquida de Alta Pressão , Ácido Glicirretínico/química , Masculino , Espectrometria de Massas , Camundongos , Sulfetos/efeitos adversos
4.
J Vet Emerg Crit Care (San Antonio) ; 30(3): 302-307, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32077228

RESUMO

OBJECTIVE: To describe a case series of systemic lime sulfur toxicosis secondary to topical administration in 2 cats. CASE SUMMARY: Two cats from the same household that were being previously treated for Microsporum canis were presented following topical administration of an incorrectly diluted lime sulfur dip. A 30% solution was used rather than the recommended 3% solution, resulting in a 10-fold concentration overdose. The cats presented to the emergency service 1 hour after dermal application of the lime sulfur product at home. The first cat, a 2-year-old female, intact Cornish Rex, had severe hypotension, bradycardia, and hypothermia. Chemical burns were also present on the ventrum and paws. Clinicopathological data revealed profound acid-base disturbances, hypercalcemia, hyperphosphatemia, and azotemia. After aggressive fluid resuscitation, electrolyte supplementation, and treatment, the patient was stabilized and discharged after 5 days of hospitalization; full recovery was later reported. The second littermate, also a 2-year-old female, intact Cornish Rex, presented the following day with similar clinical signs, physical examination findings, and clinicopathological findings. After supportive care and 2 days of hospitalization, the patient was also discharged and reported to fully recover. NEW OR UNIQUE INFORMATION PROVIDED: This case series is the first to report systemic toxicosis secondary to dermal exposure of lime sulfur. As lime sulfur is commonly used in veterinary medicine for the treatment of ectoparasites, veterinary professionals should be aware of the significant signs of poisoning that can be seen as a result of iatrogenic dosing errors by pet owners or veterinary professionals.


Assuntos
Antifúngicos/efeitos adversos , Compostos de Cálcio/efeitos adversos , Doenças do Gato/induzido quimicamente , Sulfetos/efeitos adversos , Administração Tópica , Animais , Anti-Infecciosos , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Compostos de Cálcio/administração & dosagem , Compostos de Cálcio/uso terapêutico , Doenças do Gato/tratamento farmacológico , Gatos , Feminino , Microsporum , Sulfetos/administração & dosagem , Sulfetos/uso terapêutico
5.
Toxicol Mech Methods ; 29(9): 702-709, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364917

RESUMO

Leukopenia is the early clinical manifestation of benzene poisoning. The aim of our research was to evaluate the preventive effects of three kinds of garlic preparations on benzene induced leukopenia. The mouse model of Leukopenia was established with benzene orally. At the same time, mice were administrated with garlic homogenate (GH), garlic oil (GO) or diallyl trisulfide (DATS) as preventional measures. The counts of white blood cells (WBC), the organ indexes, pathological examinations, blood biochemical parameters, weight gains, and food intakes were evaluated to observe the protective effect and potential adverse events. The results demonstrated that the counts of WBC increased by 144.04%, 140.07%, and 148.34%, respectively, after intervention by GH (400 mg/kg), GO (60 mg/kg) and DATS (30 mg/kg), compared with that in the model group. The spleen and thymus indexes in the benzene model group were 44.99% and 54.04% lower than those in the blank control group, the number of spleen nodules reduced and the thymus atrophy, which were restored by three garlic preparations at different degree. The results suggested that the three preparations all could prevent the leukopenia and protect the organ injuries induced by benzene. However, the spleen index and weight gains revealed that GH and GO brought more adverse events than DATS.


Assuntos
Compostos Alílicos/farmacologia , Benzeno/toxicidade , Alho/química , Leucopenia/prevenção & controle , Preparações de Plantas/farmacologia , Sulfetos/farmacologia , Compostos Alílicos/efeitos adversos , Animais , Modelos Animais de Doenças , Contagem de Leucócitos , Leucopenia/sangue , Leucopenia/induzido quimicamente , Masculino , Camundongos Endogâmicos , Preparações de Plantas/efeitos adversos , Baço/efeitos dos fármacos , Baço/patologia , Sulfetos/efeitos adversos , Timo/efeitos dos fármacos , Timo/patologia
6.
J Pharmacol Sci ; 140(2): 162-170, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31285125

RESUMO

QTc prolongation has been observed during arsenic trioxide and realgar's clinical use, and become a huge obstacle for the application. Our lab has obtained the soluble arsenic from realgar named realgar transforming solution or RTS. In this study, we first evaluated the cytotoxicity on NB4 cell and found that RTS could remarkably inhibit proliferation of NB4 than arsenic trioxide. Then we figured out the QTc prolongation of RTS treatment contrasted with arsenic trioxide; results revealed that arsenic trioxide prolonged corrected QTc of mice by 20.1% and showed 1.9-fold higher cytotoxicity on H9c2 cell than RTS. On the contrary, there could not find any QTc prolongation of mice in RTS treatment. Also, arsenic trioxide elevated the intercellular calcium accumulation of H9c2 cell by 2.02-fold v.s control and RTS. HE staining and Masson's trichrome staining had shown that there was no injured section after RTS treatments. IK1 currents of rat ventricular cardiomyocytes were diminished by 45.0% after treating with arsenic trioxide while RTS showed no significance than the control group. The results above indicated that RTS could serve as an alternative arsenic agent on leukemia and had a lower risk of cardiotoxicity.


Assuntos
Arsenicais , Cardiotoxicidade/etiologia , Sulfetos/toxicidade , Animais , Arsenicais/efeitos adversos , Arsenicais/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Leucemia/tratamento farmacológico , Síndrome do QT Longo/induzido quimicamente , Masculino , Camundongos , Ratos Wistar , Risco , Soluções , Sulfetos/efeitos adversos , Sulfetos/uso terapêutico
7.
Fish Shellfish Immunol ; 92: 230-240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31200069

RESUMO

In this study, we explored the individual and combined effects of ammonia-N and sulfide stress (1 mg/L sulfide and 15 mg/L ammonia-N) on the oxidation resistance, immune response and intestinal health of Litopenaeus vannamei during 72 h exposure. The total antioxidant capacity (T-AOC), malonaldehyde (MDA) and nitric oxide (NO) content, superoxide dismutase (SOD) and catalase activity (CAT), the immune-relative gene (caspase-3, hsp70 and IMD) expression in hepatopancreas and intestine of L.vannamei and the intestinal microbiota were measured. The result showed that MDA and NO contents in hepatopancreas of L. vannamei in all treatment groups increased and remain were at high levels at the end of the stress exposure. The L. vannamei employ antioxidant defense system by increasing the activities of T-AOC, SOD and CAT enzymes in hepatopancereas and intestine to reduce oxidant damage. More severe damages with combined ammonia-N and sulfide stress to antioxidant systems were observed. The gene expression results also demonstrated that antioxidant capacity of L. vannamei was severely impaired and the apoptosis cell was initiated under the ammonia-N and sulfide stress. In addition, the environmental stress also reshaped the intestinal microbial community structure of L. vannamei that a number of original genera decreased, such as Cellvibrio, Vibrio and Rheinheimera; some new genera increased or appeared, such as Photobacterium in all treatment groups, Arcobacter and Fusibacter in sulfide stress group. Therefore, the health of L. vannamei was severely impacted when exposed to the stress of ammonia nitrogen and sulfide and these two factors can have weak synergic effects.


Assuntos
Amônia/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Nitrogênio/efeitos adversos , Penaeidae/efeitos dos fármacos , Sulfetos/efeitos adversos , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Oxirredução , Penaeidae/genética , Penaeidae/imunologia , Penaeidae/microbiologia , Estresse Fisiológico
8.
Mol Biol Rep ; 46(4): 4245-4257, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31111368

RESUMO

Sulfide and hypoxia threaten marine organisms in various ways. Anadara broughtonii, a commercial marine bivalve in China which has great potential exposure to sulfide and hypoxia, was selected to test the responses to these stresses. Digital gene expression profile (DGE) analysis was performed on the juveniles' gills after exposed to normal condition (CG group), hypoxia (LO group), and low/high concentration of sulfide (LS/HS group, administered in hypoxia), respectively, using RNA-seq technology. A total of over 30 million clean reads were filtered from each DGE library and over 90% of them were annotated successfully. In total, 774 significant differentially expressed genes (DEGs) were detected and assigned to Gene ontology (GO) classification and KEGG Pathway enrichment analysis. The results show that many of the upregulated DEGs are related to hemoglobin, immunology, and stress responding. In the stressed A. broughtonii, cytochrome P450 and phosphoenolpyruvate carboxykinase may stimulate the glycolysis process to reduce oxygen consumption; Aminoacyl-tRNA synthetases, heat shock protein and protein disulfide isomerase probably help to maintain the genome integrity; Baculoviral IAP repeat-containing protein 2/3, mitogen-activated protein kinase and tumor necrosis factor pathways were probably responsible for protein repair, proteolysis, apoptosis and immune responses to high concentration of sulfide. Combined challenges also induced alternative oxidase and sushi repeat-containing protein, which have indistinct but probably indispensable function in invertebrates. For the first time, comprehensive transcriptome information on A. broughtonii in response to sulfide and hypoxia were provided. Our research offers new insights into the molecular mechanism behind the resistance of shellfish to sulfide and hypoxia.


Assuntos
Arcidae/genética , Transcriptoma/genética , Animais , Arcidae/metabolismo , China , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Hipóxia/genética , Análise de Sequência de DNA/métodos , Sulfetos/efeitos adversos
9.
Basic Clin Pharmacol Toxicol ; 125(3): 289-303, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30843331

RESUMO

Sodium cyanide (NaCN) is a commonly and widely used industrial and laboratory chemical that is highly toxic. Its availability and rapid harmful/lethal effects combine to make cyanide a potential foodborne/waterborne intentional-poisoning hazard. Effective antidotes to cyanide poisoning are currently approved only for intravenous administration. Therefore, an effective cyanide antidote that can be administered intramuscularly in pre-hospital and/or mass-casualty settings is needed. Dimethyl trisulfide (DMTS) is a naturally occurring substance used as a flavour enhancer in foods. DMTS has shown antidotal efficacy in cyanide poisoning and is thought to act as both a sulphur donor and partial methaemoglobin inducer. In this study, an intramuscular injection of DMTS (6.25-200 mg/kg) was given to rats 1 minute after an oral dose of NaCN (98.2 mg/kg; twice the median lethal dose) to test the antidotal efficacy and safety of DMTS treatment. Toxic signs and survival were examined along with behavioural function (up to 30 hour after ingestion) using a previously established operant behavioural model. A large range of DMTS doses (6.25-100 mg/kg) increased survival after oral cyanide poisoning, and the lower DMTS doses (6.25-25 mg/kg) also proved to be behaviourally and physiologically safe. Larger DMTS doses (50-200 mg/kg) produced side effects (ie, inflammation and limping) that were more severe and protracted than those observed at lower DMTS doses. The 25 mg/kg DMTS proved to be the most efficacious (increasing survival from 20% to 75%) and also produced minimal side effects (eg, inflammation) that resolved within 24-72 hour. Thus, DMTS shows promise as an intramuscularly administered cyanide antidote useful for prompt pre-hospital or mass-casualty emergency medical treatment.


Assuntos
Antídotos/administração & dosagem , Primeiros Socorros/métodos , Envenenamento/tratamento farmacológico , Cianeto de Sódio/envenenamento , Sulfetos/administração & dosagem , Administração Oral , Animais , Antídotos/efeitos adversos , Técnicas de Observação do Comportamento , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Injeções Intramusculares , Dose Letal Mediana , Masculino , Incidentes com Feridos em Massa , Modelos Neurológicos , Envenenamento/mortalidade , Envenenamento/psicologia , Ratos , Cianeto de Sódio/administração & dosagem , Sulfetos/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
10.
Food Chem Toxicol ; 120: 544-551, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30075317

RESUMO

Methyl propyl trisulfide is a flavoring substance found in foods such as garlic and onions. At the request of the European Food Safety Authority (EFSA) for additional toxicological data on methyl propyl trisulfide, groups of Sprague-Dawley rats (10/sex/group) were gavaged with 0 (corn oil vehicle control), 0.5, 2, or 6 mg methyl propyl trisulfide/kg bw/day in a 90-day GLP-compliant study. No effects on clinical observations, hematology and clinical chemistry parameters, organ weights, or macroscopic and histopathological examinations were found attributable to ingestion of methyl propyl trisulfide. The oral no-observed-adverse-effect level (NOAEL) for rats of both sexes was the highest dose tested of 6 mg/kg bw/day.


Assuntos
Alcenos/efeitos adversos , Aromatizantes/efeitos adversos , Sulfetos/efeitos adversos , Administração Oral , Alcenos/administração & dosagem , Animais , Aromatizantes/administração & dosagem , Nível de Efeito Adverso não Observado , Ratos Sprague-Dawley , Sulfetos/administração & dosagem
11.
Clin Ther ; 40(8): 1347-1356, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30017171

RESUMO

PURPOSE: Imrecoxib is one type of cyclooxygenase-2 inhibitor with the capability of reducing the potential cardiovascular risk caused by other NSAIDs. Co-administration with other medications can affect the cytochrome P450 (CYP) 2C9 enzyme function; thus, imrecoxib metabolism can be affected. The purpose of this research was to evaluate the effects of fluconazole, which is known to inhibit CYP2C9, on imrecoxib's pharmacokinetic (PK) parameters. METHODS: In this single-center, single-arm, open-label, self-controlled study, 12 healthy Chinese male volunteers (mean [SD] age, 22.6 [2.43] years) received the following 2 treatments separated by a washout period of 8 days under a fasting state: (1) a single oral dose of imrecoxib 100 mg; and (2) fluconazole 200 mg/d over 6 days followed by concurrent dosing of imrecoxib 100 mg and fluconazole 200 mg. Plasma concentrations of imrecoxib (M0) and its metabolites (4'-hydroxymethyl metabolite [M1] and 4'-carboxylic acid metabolite [M2]) for PK analysis were obtained at 0 (baseline) and 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, and 72 hours after imrecoxib dosing. Safety and tolerability assessments were performed throughout the study. FINDINGS: All subjects completed the study. There was 1 adverse event; drug-induced liver damage in 1 subject occurred after he received imrecoxib plus fluconazole, and the subject recovered without any sequelae. Coadministration with fluconazole resulted in much higher plasma imrecoxib concentrations, with an increase of 88% in Cmax and 72% in AUC0-t compared with only imrecoxib treatment, which showed that fluconazole may increase plasma exposure to imrecoxib. Fluconazole also caused a small, but not clinically relevant, decrease in M1 and M2 mean Cmax (13% and 14%, respectively), but there was minimal change in M1 and M2 mean AUC0-t (3% and 2%). However, there were no statistically significant differences in vital signs, clinical laboratory test results, ECGs, or adverse events between treatments. IMPLICATIONS: Concurrent administration of imrecoxib and fluconazole did not seem to change imrecoxib's safety profile. The ratio (imrecoxib + fluconazole/imrecoxib) for AUC0-t was 1.72 (90% CI, 1.41-2.11) and for Cmax it was 1.88 (90% CI, 1.59-2.21). Hence, it is necessary to adjust the imrecoxib dose when it is concurrently used with other CYP2C9 inhibitors.


Assuntos
Antifúngicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacocinética , Fluconazol/farmacologia , Pirróis/farmacocinética , Sulfetos/farmacocinética , Administração Oral , Adulto , Área Sob a Curva , China , Estudos Cross-Over , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/sangue , Interações Medicamentosas , Voluntários Saudáveis , Humanos , Masculino , Pirróis/efeitos adversos , Pirróis/sangue , Distribuição Aleatória , Sulfetos/efeitos adversos , Sulfetos/sangue , Adulto Jovem
12.
Medicine (Baltimore) ; 97(25): e10788, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29923970

RESUMO

RATIONALE: Vortioxetine is a new multimodal antidepressant approved by the Food and Drug Administration for the treatment of Major Depressive Disorder and recently introduced in Europe. While antidepressant properties of vortioxetine and its tolerability have been demonstrated by preclinical and clinical studies data on the safety of vortioxetine after overdose are still lacking. PATIENT CONCERNS: A 50-year-old Caucasian man presenting a severe depressive episode that in a suicide attempt he took vortioxetine at 250 mg. DIAGNOSES: Suicide attempt by vortioxetine in a patient affected by Major Depressive Disorder. INTERVENTIONS: General evaluations and gastric lavage with 2 L of water plus 50 g of activated charcoal was performed. After 12 hours of clinical stability, the patient was discharged from the emergency department and considering the suicidal ideation he was admitted to the inpatients psychiatric department. OUTCOMES: After vortioxetine overdose the patient displayed no clinical signs or symptoms resulting from the exposure suggesting a good safety in overdose. LESSON: Overdose safety of different antidepressant drugs is a matter of great considering that overdose in individuals affected by Major Depressive Disorder frequently involves prescribed antidepressants. Previous studies showed wide variation in the relative toxicity of different antidepressant drugs with higher toxicity for tricyclic antidepressants, followed by venlafaxine bupropion and mirtazapine and lower for selective serotonin reuptake inhibitors. By now there is limited clinical trial experience regarding human overdose with vortioxetine and the maximum single dose tested was 75 mg in men associated with increased rates of nausea, dizziness, diarrhea, abdominal discomfort, generalized pruritus, somnolence, and flushing. Even if there is still limited available evidence and further investigation is needed to better understand the potential risk of vortioxetine overdose; from our case, it seems that vortioxetine overdose at 250 mg (12 times the common daily dose) showed no signs or symptoms resulting from the exposure suggesting a good safety in overdose.


Assuntos
Transtorno Depressivo Maior , Overdose de Drogas , Piperazinas , Tentativa de Suicídio/psicologia , Sulfetos , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Carvão Vegetal/administração & dosagem , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Overdose de Drogas/etiologia , Overdose de Drogas/fisiopatologia , Overdose de Drogas/psicologia , Overdose de Drogas/terapia , Lavagem Gástrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Escalas de Graduação Psiquiátrica , Ideação Suicida , Sulfetos/administração & dosagem , Sulfetos/efeitos adversos , Resultado do Tratamento , Vortioxetina
13.
J Clin Psychopharmacol ; 38(3): 172-179, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29596146

RESUMO

BACKGROUND: Obesity and depression are common comorbid conditions. The objective of the study was to evaluate the effect of obesity on the pharmacokinetics of the serotonergic antidepressant vortioxetine. METHODS: Vortioxetine pharmacokinetics were evaluated in 16 otherwise healthy obese volunteers (mean weight, 119 kg; mean body mass index (BMI) 41.8 kg/m) and in 14 normal-weight subjects (mean weight, 68 kg; mean BMI, 23.0 kg/m) matched for age. All subjects received a single 5-mg oral dose of vortioxetine once daily for 29 days. Pre-dose plasma vortioxetine concentrations were measured during the 29 days of dosing, and during a 4-week washout period after the last dose. Full 24-hour profiles were obtained after the first and last doses. RESULTS: Vortioxetine accumulated extensively over the 29 days; the accumulation ratio was not significantly different between obese and control groups (means: 5.24 and 4.46, respectively). Steady-state concentration (Css) and steady-state clearance also did not differ between groups. However mean washout half-life (T1/2) was significantly prolonged in obese vs. control subjects (3.26 days vs. 2.21 days, P < 0.01). Up to 89% of the individual variability in T1/2 was explained by the product of Css and numeric indicators of the degree of obesity. CONCLUSIONS: The half-life of vortioxetine washout after discontinuation of therapy is significantly prolonged in obese individuals compared to normal weight controls. To avoid a potential risk of serotonin syndrome, obese patients who plan to change their medication from vortioxetine to a monoamine oxidase inhibitor (MAOI) should extend the time between vortioxetine discontinuation and MAOI initiation beyond what is recommended in the product label.


Assuntos
Obesidade/metabolismo , Piperazinas/farmacocinética , Inibidores de Captação de Serotonina/farmacocinética , Sulfetos/farmacocinética , Adolescente , Adulto , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Inibidores de Captação de Serotonina/efeitos adversos , Sulfetos/efeitos adversos , Vortioxetina , Adulto Jovem
14.
J Affect Disord ; 229: 421-428, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29331703

RESUMO

BACKGROUND: Major Depressive Disorder (MDD) is a complex disease characterized by emotional, physical and cognitive symptoms. We explored the efficacy of vortioxetine versus placebo on outcomes of cognition, functioning and mood symptoms in working patients with depression, using paroxetine as an active reference. METHODS: Gainfully employed patients (18-65 years, N = 152) with MDD were randomized 1:1:1 to 8 weeks' double-blind, parallel treatment either with vortioxetine (10mg/day) or paroxetine (20mg/day), or with placebo. The primary efficacy measure was the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements, and the key secondary efficacy measure was the University of San Diego Performance-based Skills Assessment - Brief (UPSA-B), analyzed using analysis of covariance (last observation carried forward). RESULTS: At week 8, DSST and UPSA-B performance had improved relative to baseline in all treatment groups, with no statistically significant differences between treatment groups. While improvements in mood were comparable for vortioxetine and paroxetine, numerical improvements in cognitive performance (DSST) were larger with vortioxetine. Vortioxetine significantly improved overall cognitive performance and clinician-rated functioning relative to placebo. The majority of adverse events were mild or moderate, with nausea being the most common adverse event for vortioxetine. LIMITATIONS: Small sample sizes implied limited statistical power. CONCLUSION: This explorative study showed no significant differences versus placebo in DSST or UPSA-B performance at week 8. However, secondary results support vortioxetine as an effective and well-tolerated antidepressant, supporting an added benefit for cognition and functioning, which could have particular therapeutic relevance for the working patient population.


Assuntos
Cognição/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Adulto , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Paroxetina/farmacologia , Paroxetina/uso terapêutico , Piperazinas/efeitos adversos , Sulfetos/efeitos adversos , Resultado do Tratamento , Vortioxetina , Escalas de Wechsler
15.
Psychiatry Clin Neurosci ; 72(2): 64-72, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28858412

RESUMO

AIM: This study assessed the efficacy and safety of vortioxetine in adults with major depressive disorder. METHODS: In this double-blind, placebo-controlled study, 600 patients with major depressive disorder were randomly assigned (1:1:1:1) to receive vortioxetine 5, 10, or 20 mg, or placebo once daily for 8 weeks. The primary end-point was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8, evaluated by the last-observation-carried-forward method. Secondary end-points included response (≥ 50% decrease in the MADRS total score from baseline) and remission (MADRS total score ≤ 10), Clinical Global Impression Scale-Improvement, and change from baseline in Sheehan Disability Scale. Adverse events were summarized. RESULTS: Vortioxetine failed to show significant differences from placebo in the primary end-point. Nominally significant improvements over placebo were observed for vortioxetine doses of 10 and 20 mg when the primary end-point was evaluated using the mixed model for repeated measures as the secondary analysis, and 10 mg in secondary measures of response and patient functioning. Vortioxetine was well tolerated. Nausea, constipation, dry mouth, dizziness, and insomnia each occurred at a >twofold higher rate than placebo. Discontinuation symptom scores were comparable between all groups after 1 and 2 weeks following withdrawal of the study drug. CONCLUSION: While vortioxetine failed to meet significance versus placebo in the primary efficacy analysis, there was evidence of efficacy for the 10- and 20-mg doses in secondary analyses. Vortioxetine was safe and well tolerated. Additional studies appear warranted.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Piperazinas/farmacologia , Inibidores de Captação de Serotonina/farmacologia , Sulfetos/farmacologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/efeitos adversos , Sulfetos/administração & dosagem , Sulfetos/efeitos adversos , Vortioxetina
16.
Psychiatry Clin Neurosci ; 72(2): 103-115, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29160598

RESUMO

AIM: Safety and efficacy of vortioxetine (5-20 mg/day) in Japanese patients with major depressive disorder were evaluated in two phase 3 studies consisting of a short-term, 8-week, placebo-controlled, double-blind study followed by a long-term, 52-week, open-label extension study. METHODS: The primary end-point of the short-term study was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8. The primary objective of the extension study was vortioxetine's long-term safety; efficacy end-points included change in MADRS total score, Clinical Global Impression Scale (CGI)-Severity (S) score from the long-term study baseline, and CGI-Improvement (CGI-I) score over 52 weeks. RESULTS: Of the 366 randomized patients, 338 completed the short-term study, and 119 patients continued into the extension study. Primary (analysis of covariance) and secondary (mixed model for repeated measurements) analyses in the short-term study showed numerically greater, but not statistically significant, decreases in change in MADRS total score from baseline between the vortioxetine and placebo groups at week 8. In the long-term study, 86.6% of patients reported at least one treatment-emergent adverse event, with the most common being nasopharyngitis (40.3%) and nausea (21%). MADRS total score and CGI-I and CGI-S scores improved with continued vortioxetine treatment from baseline of the open-label study to week 52. CONCLUSION: Vortioxetine failed to meet significance versus placebo in the primary efficacy analysis at week 8 in the short-term study. The extension trial indicated continued improvement of depressive symptoms from baseline of this study throughout the 52-week treatment period. Vortioxetine treatment was safe and well tolerated in both studies.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Piperazinas/farmacologia , Inibidores de Captação de Serotonina/farmacologia , Sulfetos/farmacologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Escalas de Graduação Psiquiátrica , Projetos de Pesquisa , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/efeitos adversos , Sulfetos/administração & dosagem , Sulfetos/efeitos adversos , Vortioxetina
17.
J Affect Disord ; 228: 1-12, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29197738

RESUMO

BACKGROUND: Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants. METHODS: We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses. RESULTS: Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low. LIMITATIONS: Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses. CONCLUSIONS: Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Ciclopropanos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Piperazinas/uso terapêutico , Sulfetos/uso terapêutico , Cloridrato de Vilazodona/uso terapêutico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Ciclopropanos/efeitos adversos , Humanos , Milnaciprano , Metanálise em Rede , Piperazinas/efeitos adversos , Sulfetos/efeitos adversos , Cloridrato de Vilazodona/efeitos adversos , Vortioxetina
18.
J Psychiatr Res ; 96: 247-259, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29127931

RESUMO

In last decade, the US FDA has approved three new antidepressants: vortioxetine, levomilnacipran, and vilazodone. Many studies have researched the effects of these antidepressants on major depressive disorder (MDD), but they have not determined the optimum dosage. This meta-analysis investigated the efficacies of these three drugs at different dosages in the treatment of MDD. The PubMed, Embase, Cochrane Library, psycINFO, and ClinicalTrials.gov databases were searched to identify relevant literature. The primary outcomes were efficacy [quantified as the change from baseline in total score on the Montgomery-Asberg Depression Rating Scale (MADRS)] and tolerability (discontinuations due to adverse events). The effect size was quantified as the weighted mean difference for continuous data and the risk ratio (RR) for dichotomous data. Overall 22 studies were included. The changes in the MADRS total score were significantly higher for vortioxetine at 5, 10, 20, and 10-20 mg/day than for placebo. The tolerability was significantly worse for 20 mg/day vortioxetine than for placebo (RR = 1.84, 95% confidence interval = 1.13 to 3.02). In addition, increasing the dosage improved the efficacy of vortioxetine but worsened the tolerability. Levomilnacipran and vilazodone at any dosage produced a significantly higher mean change from baseline in the MADRS total score and a worse tolerability than for placebo. In conclusion, considering both efficacy and tolerability, 10 mg/day vortioxetine might be optimal for the treatment of MDD. The long-term efficacy and safety of vortioxetine needed to be investigated, and more studies of levomilnacipran and vilazodone are needed to define their optimal dosages.


Assuntos
Antidepressivos/administração & dosagem , Ciclopropanos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Piperazinas/administração & dosagem , Inibidores de Captação de Serotonina/administração & dosagem , Sulfetos/administração & dosagem , Cloridrato de Vilazodona/administração & dosagem , Antidepressivos/efeitos adversos , Ciclopropanos/efeitos adversos , Humanos , Milnaciprano , Piperazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Sulfetos/efeitos adversos , Cloridrato de Vilazodona/efeitos adversos , Vortioxetina
19.
Asian J Psychiatr ; 30: 152-156, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28942181

RESUMO

BACKGROUND: Signal detection is one of the most advanced and emerging field in pharmacovigilance. It is a modern method of detecting new reaction (which can be desired or undesired) of a drug. It facilitates early adverse drug reaction detection which enables health professionals to identify adverse events that may not have been identified in pre-marketing clinical trials. Vortioxetine, the first mixed serotonergic antidepressant was initially approved by the US Food and Drug Administration (USFDA) on September 30, 2013 for the treatment of adults with Major Depressive Disorder (MDD). This study was to identify the signal strength for vortioxetine associated ADRs using data mining technique in USFDA Adverse Event Reporting System (AERS) database. METHODOLOGY: Most commonly used three data mining algorithms, Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR) and Information Component (IC) were selected for the study and they were applied retrospectively in USFDA AERS database from 2015Q1 to 2016Q3. A value of ROR-1.96SE >1, PRR≥2, IC- 2SD>0 were considered as the positive signal. RESULT: A study population of 61,22,000 were reported all over the world. Among which 3481 reactions were associated with vortioxetine which comprised of 632 unique events encompassed with 27 clinically relevant reactions. ROR, PRR and IC showed positive signal for weight loss, agitation, anger, ketoacidosis, insomnia and abnormal dreams. CONCLUSION: The present study suggests that vortioxetine may result in these adverse events. Further pharmacoepidemiologic studies are necessary to confirm this conclusion and to improve the precision of the prevalence and/or the risk factors of this ADRs.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Mineração de Dados/métodos , Transtorno Depressivo Maior/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Farmacovigilância , Piperazinas/efeitos adversos , Inibidores de Captação de Serotonina/efeitos adversos , Sulfetos/efeitos adversos , Humanos , Estados Unidos , United States Food and Drug Administration/estatística & dados numéricos , Vortioxetina
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