ABSTRACT
ObjectiveTo evaluate the efficacy and safety of agomelatin and selective serotonin reuptake inhibitors （SSRIs） in the treatment of depressive disorder via network Meta-analysis. MethodsThe literature databases such as China National Knowledge Network （CNKI）， Wanfang Data Knowledge Service Platform， VIP Database for Chinese Technical Periodical （VIP）， Chinese Biomedical Literature Database （CBM）， PubMed， Embase and Cochrane Library were searched from the inception to November 2021. Based on the preset inclusion and exclusion criteria， literature screening， quality assessment of methodology and data extraction were conducted by two researchers separately， then statistical analysis was carried out using ADDIS software. ResultsA total of 7 256 patients with depressive disorder in 22 randomized controlled trials were included. According to the consistency assessed in Bayesian network Meta-analysis and the estimation of the probability of being the best treatment， escitalopram （P=0.63） ranked first for response rate and paroxetine （P=0.31） was associated with the best ranking for cure rate in terms of the effectiveness， meantime， paroxetine （P=0.44） had the highest adverse events risk and sertraline （P=0.74） had the highest study drop-outs proportion in terms of safety. ConclusionEscitalopram and paroxetine may be superior to sertraline， agomelatine， citalopram and fluoxetine in the treatment of depressive disorder， furthermore， paroxetine and sertraline demonstrate poor safety profiles.
ABSTRACT
Objective: The aim of this investigation was the development and characterization of Agomelatin-loaded liquid crystalline (AM-LC) nanoparticles for improved topical application. Methods: AM-LC was formulated with the glyceryl monooleate (GMO) and poloxamer 407 as structure forming agent (lipid) and surfactant respectively, by using emulsification of GMO and poloxamer in water using a hydrotrope (Cubosomes) formation method. The obtained dispersion was characterized for particle size, PDI, zeta potential, entrapment efficiency, surface morphology, in vitro studies. Further, conversion optimised formulation in to cubic gel by incorporating 0.5% w/w of carbopol 934P. The prepared gel was characterized by rheological measurements, surface pH and ex vivo permeation studies through the rat skin. Results: The average particle size of formulations was ranging from 187.6±3.97nm to 225.8±7.54nm and ZP from -14.5±4.65 to -23.5±3.86mV. In vitro drug release from cubosomes exhibited sustained release profile and the optimized formulation (F2) showed cumulative drug release of 83.96±2.43% during 24h. Transmission electron microscopic photographs confirmed that the formed liquid crystalline nanoparticles were cubic in shape. Results suggested that cubic gel exhibited a retarded release rate (53.5 ± 3.21%) than the control gel (95.33 ± 2.28%) containing 0.1% drug solution. Conclusion: The obtained results indicated that cubic gel would be a promising carrier for topical delivery of agomelatin into and across the skin.
ABSTRACT
Los modelos neurobiológicos de la depresión han evolucionado más allá de la teoría monoaminérgica, que fue construida luego del advenimiento de las drogas antidepresivas en la década de 1950. Actualmente se considera que la depresión implica una amplia gama de neurotransmisores, incluyendo a la dopamina y el glutamato, y a prácticamente la totalidad del sistema nervioso central. La evidencia emergente está redefiniendo la depresión como una enfermedad crónica y sistémica que puede deteriorar la función neuroendocrina, los ritmos biológicos y las respuestas inmunes, y como una enfermedad que, de no ser tratada, puede conducir a la demencia. Diferentes abordajes de investigación, desde la biología molecular hasta los estudios clínicos, han ofrecido tanto nuevos conocimientos acerca de los mecanismos fisiológicos implicados como también indicios para desarrollar terapias antidepresivas efectivas en respuesta a los mismos. Además de los métodos ya bien establecidos, como los inhibidores de la recaptación de monoaminas y la terapia cognitivo-conductual, estos pueden incluir drogas anti-inflamatorias no esteroides, prescripción de ejercicio físico, tratamientos somáticos y toda una nueva generación de drogas antidepresivas dotadas de modos de acción originales. A medida que el manejo de la depresión se torna cada vez más multifacético, los médicos serán capaces de optimizar los resultados clínicos para sus pacientes integrando sinérgicamente las múltiples opciones terapéuticas disponibles.
Neurobiological models of depression have evolved far beyond the monoamine theory that was construed following the advent of antidepressant drugs in the 1950s. Depression is now seen to implicate a wide range of neurotransmitters, including dopamine and glutamate, and virtually the entire central nervous system. Emerging evidence is redefining depression as a chronic and systemic illness that may impair neuroendocrine function, biological rhythms and immune responses, and one which may lead to dementia if left untreated. Different research approaches, from molecular biology to clinical studies, have offered new insights into the physiological mechanisms involved as well as indications of how effective antidepressant therapies may develop in response to these. In addition to well-established methods, like monoamine reuptake inhibitors and cognitive behavioral therapy, these may include non-steroid anti-inflammatory drugs, prescription of physical exercise, somatic treatments and a whole new generation of antidepressant drugs endowed with original modes of action. As the management of depression becomes increasingly multifaceted, clinicians will be able to optimize clinical outcomes for their patients by synergistically integrating the multiple therapeutic options available.