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Aust N Z J Psychiatry ; 48(7): 663-71, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24604920


OBJECTIVE: Agomelatine is a new antidepressant with unique melatonin receptor type 1A (MTNR1A) and 1B ( MTNR1B) agonism and serotonergic receptor 5-hydroxytryptamine receptor 2C (5-HT-2C) antagonism. Several studies of patients with major depressive disorder (MDD) have confirmed the superior efficacy and safety of agomelatine in comparison with established treatments, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This meta-analysis comprehensively shows the efficacy, acceptability, and safety of agomelatine in comparison with SSRIs and SNRIs used as antidepressants in MDD. METHOD: Comprehensive electronic database searches were performed to identify reports of head-to-head randomized controlled trials that have compared agomelatine with SSRIs or SNRIs in terms of efficacy/effectiveness in treating MDD. Response and remission rates at both acute (6-12 weeks) and follow-up (24 weeks) phases, Clinical Global Impression-Improvement Scale response and remission rates, changes in depression scale scores, improvements in subjective sleep, dropout rates, and side effect rates were extracted and analysed. RESULTS: The meta-analysis included six head-to-head trials involving 1871 patients. In the acute phase, agomelatine had higher response rates (relative risk (RR) 1.08, 95% confidence interval (CI) 1.02-1.15) compared to SSRIs and SNRIs. In the remission analysis, only acute remission rates (RR 1.12, 95% CI 1.01-1.24) significantly differed. The action of agomelatine was superior on the Leeds Sleep Evaluation Questionnaire-Quality of Sleep score (mean difference 4.05, 95% CI 0.61-7.49). Discontinuation due to inefficacy did not differ between agomelatine and SSRIs/SNRIs (RR 0.74, 95% CI 0.42-1.28). Compared to SSRIs and SNRIs, however, agomelatine revealed a lower rate of discontinuation due to side effects (RR 0.38, 95% CI 0.25-0.57). CONCLUSIONS: Agomelatine has significantly higher efficacy and potential acceptability compared to SSRIs and SNRIs when treating MDD. However, the difference in efficacy is not considered clinically relevant. Because of its unique chronobiotic effects, agomelatine may be useful for the management of some MDD patients with circadian disturbance.

Acetamidas/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Acetamidas/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Resultado do Tratamento
Diagn Microbiol Infect Dis ; 75(1): 94-100, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23116904


This retrospective observational study evaluated the impact of antimicrobial consumption on antimicrobial susceptibility among aerobic Gram-negative bacteria after introducing ertapenem to the formulary of a teaching hospital (1130 beds) in northern Taiwan. Data on consumption of various antimicrobial agents, expressed as defined daily dose/1000 patient-days (DDD/1000 PD), were collected retrospectively from hospital pharmacy records 2 years before and 5 years after the introduction of ertapenem (October 2005). During the study period, the consumption of ampicillin and aminoglycosides decreased significantly. In contrast, the consumption of cefoxitin, ceftazidime, cefpirome, piperacillin-tazobactam, carbapenems (ertapenem, imipenem, and meropenem), and fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) increased significantly over time. There was a significant increase in the rate of susceptibility of Escherichia coli to ampicillin, cefotaxime, ceftazidime, piperacillin-tazobactam, cefpirome, amikacin, and levofloxacin; an increase in the rate of susceptibility of Klebsiella pneumoniae to ceftazidime, cefepime, cefpirome, piperacillin-tazobactam, meropenem, levofloxacin, and amikacin; a significant decrease in the rate of susceptibility of Pseudomonas aeruginosa to meropenem; and a significant decrease in the rate of susceptibility of Acinetobacter baumannii to ceftazidime, carbapenems, ciprofloxacin, and levofloxacin. The rate of antibiotic susceptibility to ertapenem of extended spectrum ß-lactamase producers, including E. coli and K. pneumoniae, remained stable. Usage of ertapenem was found to be negatively and significantly associated with the susceptibility rates of P. aeruginosa to meropenem and gentamicin. Significantly negative correlations were noted between the use of ertapenem and the rates of susceptibility of A. baumannii to ceftazidime, piperacillin-tazobactam, carbapenems (imipenem and meropenem), ciprofloxacin, and levofloxacin.

Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico , Centros Médicos Acadêmicos , Uso de Medicamentos/estatística & dados numéricos , Ertapenem , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Taiwan
World J Gastroenterol ; 12(43): 6955-60, 2006 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-17109516


AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment. METHODS: From July 2002 to July 2004, patients with HCC who received thalidomide treatment, were enrolled. We extracted relevant data from the patients' medical records, including history and type of hepatitis, comorbidity, serum alpha-fetoprotein (alpha-FP) level, volumetric changes in tumor, length of survival, and the dose, duration, side effects of thalidomide treatment. The tumor response was evaluated. On the basis of these data, the patients were divided into two groups: those with either partial response or stable disease (PR + SD group) and those with progressive disease (PD group). RESULTS: Two of 42 (5%) patients had a partial tumor response after treatment with thalidomide, 200 mg/d, and 9 (21%) had stable disease. Patients in the PR + SD group all had cirrhosis. Comparing patients with and without cirrhosis, the former were more likely to respond to thalidomide therapy (PR + SD: 100% vs PD: 64.5%, P = 0.041 < 0.05). Thalidomide was significantly more likely to be effective in tumors smaller than 5 cm (PR + SD: 63.6% vs PD: 25.8%, P = 0.034 < 0.05). Compared with patients with progressive disease (PD), patients in the PR + SD group had a higher total dose of thalidomide (13669.4 +/- 8446.0 mg vs 22022.7 +/- 11461.4 mg, P = 0.023 < 0.05) and a longer survival (181.0 +/- 107.1 d vs 304.4 +/- 167.1 d, P = 0.047 < 0.05). Patients with comorbid disease had a significantly greater incidence of adverse reactions than those without (93.8% vs 60.0%, P = 0.021 < 0.05). The average number of adverse reactions in each person with a comorbid condition was twice as high as in those without other diseases (2.2 +/- 1.3 vs 1.1 +/- 1.2; P = 0.022 < 0.05). CONCLUSION: Thalidomide therapy is most likely to be effective in patients with early stage small HCC, especially in those with other underlying diseases. A low dose (200 mg/d) of thalidomide is recommended to continue the treatment long enough to make it more effective.

Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
Eur J Pharm Sci ; 15(5): 417-23, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12036718


Nonivamide, a so-called synthetic capsaicin, is a substitute for capsaicin which has a similar chemical structure and pharmacological activities as those of capsaicin. The purposes of this study were to explore the in vivo pharmacodynamic responses of nonivamide in hydrogels using Wistar rat as an animal model and to correlate the in vivo results with in vitro topical application. The incorporation of Pluronic F-127 polymer into hydrogels resulted in retarded release of nonivamide. Chitosan and carboxymethylcellulose hydrogels produced higher levels of in vitro nonivamide permeation and skin distribution. The in vivo effects of nonivamide on skin perturbation and vasodilation were found to differ depending on dose and duration after topical application. Quantification of transepidermal water loss was demonstrated to correlate with the measured in vitro skin distribution of nonivamide. The various doses of nonivamide in the hydrogels did not markedly influence erythematous reactions of skin as determined by colorimetric measurements. Hydrogel formulations of nonivamide delivered more drug to the skin and produced greater pharmacodynamic activities than did cream bases of capsaicin.

Capsaicina/análogos & derivados , Capsaicina/farmacocinética , Hidrogéis/farmacocinética , Modelos Animais , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Administração Tópica , Animais , Capsaicina/farmacologia , Hidrogéis/farmacologia , Masculino , Ratos , Ratos Wistar