帕罗西汀与其他选择性5-HT再摄取抑制药疗效及安全性的meta分析

目的 评价帕罗西汀与其他选择性5-HT再摄取抑制药的疗效及安全性。方法 计算机检索Cochrane图书馆、ISI数据库、中国知网（CNKI）、维普（VIP）、万方数字化期刊数据库,纳入帕罗西汀与其他选择性5-HT再摄取抑制药疗效及安全性随机对照试验（randomized controlled trial,RCT）、系统评价和meta分析文献,对纳入文献的RCTs进行方法学质量评价和meta分析,参考纳入文献的系统评价和meta分析结论。结果 帕罗西汀与其他选择性5-HT再摄取抑制药疗效及安全性对比分析共纳入15个RCTs。2组抗抑郁总有效率差异有统计学意义（OR=1.45,95%CI=1.01~2.09,P=0.04）;治疗2周和6周后HAMD评分差异有统计学意义（MD=-2.04,95%CI=-2.59~-1.49,P<0.000 01;MD=-0.69,95%CI=-1.18~-0.21,P=0.005）;治疗6周后药物不良反应发生率差异有统计学意义（OR=0.88,95%CI=0.78~0.99,P=0.04）。结论 与其他选择性5-HT再摄取抑制药相比较,帕罗西汀的总有效率及起效速度较低,不良反应发生率较高,其不再推荐为一线抗抑郁药。     

Design,Synthesis and Evaluation of Antidepressant Activity of Novel 2‐Methoxy 1, 8 Naphthyridine 3‐Carboxamides as 5‐HT3 Receptor Antagonists

A series of novel 1,8‐naphthyridine‐3‐carboxamides as 5‐HT₃ receptor antagonists were synthesized with an intention to explore the antidepressant activity of these compounds. The title carboxamides were designed using ligand‐based approach keeping in consideration the structural requirement of the pharmacophore of 5‐HT₃ receptor antagonists. The compounds were synthesized using appropriate synthetic route from the starting material nicotinamide. 5‐HT₃ receptor antagonism of all the compounds, which was denoted in the form of pA₂ value, was determined in longitudinal muscle myenteric plexus preparation from guinea‐pig ileum against 5‐HT₃ agonist, 2‐methyl‐5‐HT. Compound 8g (2‐methoxy‐1, 8‐naphthyridin‐3‐yl) (2‐methoxy phenyl piperazine‐1‐yl) methanone was identified as the most active compound, which expressed a pA₂ value of 7.67. The antidepressant activity of all the compounds was examined in mice model of forced swim test (FST); importantly, none of the compounds was found to cause any significant changes in the locomotor activity of mice at the tested dose levels. In FST, the compounds with considerably higher pA₂ value exhibited promising antidepressant‐like activity, whereas compounds with lower pA₂ value did not show antidepressant‐like activity as compared to the control group.     

Effects of single and multiple doses of dexnafenodone,imipramine and placebo on sleep of young healthy volunteers

The effects on polygraphically recorded sleep of single and repeated doses of dexnafenodone (20 mg daily) were determined in 12 young, healthy subjects, and compared to those of imipramine (75 mg daily: six subjects) and placebo (six subjects). After two adaptation nights, sleep was recorded at baseline (night 0), and after the first (night 1) and last (night 5) evening administration of the study drugs. REM sleep was substantially inhibited in both nights under the two active treatments, whereby the effect appeared immediately. With the exception of slow wave sleep (SWS), which was more reduced in night 1 under imipramine than under dexnafenodone, the other sleep stages were essentially unchanged. Time awake during bed rest increased under both active treatments, with a more rapid increase under dexnafenodone. Dexnafenodone, a potent inhibitor of noradrenaline, and to a lesser degree of serotonin reuptake, induced changes in the pattern of sleep which are comparable to those of non-sedating tricyclic antidepressants. The mode of action as well as the pharmacodynamic profile of dexnafenodone led to the expectation that this new substance will show antidepressive activity on a clinical level.     

Brain-derived neurotrophic factor and post-stroke depression

Brain-derived neurotrophic factor (BDNF) is well known to play a critical role in cognition. Its role in mood disorders, including post stroke depression (PSD), is also recognized with more evidence surfacing. In patients with PSD, their serum BNDF level is lower than in those without depression. Furthermore, antidepressants could enhance BDNF expression in the brain, resulting in an alleviation of depression symptoms. Such therapeutic effect can be abolished in animals with the BDNF gene deleted. In PSD patients, the presence of stroke may contribute to the development of depression, including affecting the expression of BDNF. However, the mechanisms of BDNF in the development of PSD remain largely unknown. Lower BDNF levels may have existed in some patients before stroke onset, making them vulnerable to develop depressive symptoms. Meanwhile, the hypoxic environment induced by stroke could possibly downregulate BDNF expression in the brain. Current antidepressant treatments are not specific for PSD and there is a lack of treatments to address the linkage between stroke and PSD. This review summarizes the current knowledge of BDNF in PSD. By regulating BDNF expression, a synergistic effect may be achieved when such treatments are applied together with existing antidepressants.     

An association of AKT1 gene polymorphism with antidepressant treatment response

Objectives: Nowadays it is considered that protein kinase Akt1 could be involved in pathogenesis of affective disorders. We have examined whether AKT1 gene polymorphisms are associated with antidepressant treatment response. Methods: The study included 106 Caucasian patients with depressive disorders from Siberia and 103 healthy control donors. The frequencies of single nucleotide polymorphisms rs1130214 and rs3730358 of AKT1 gene were examined. Results: A comparison of genotypic or allelic frequencies between the groups of healthy donors and depressive patients showed no statistically significant difference. No association between the polymorphisms under study and the scores according to Hamilton Depression Rating Scale 17 was found. However, an association between treatment response assessed by the Clinical Global Impression – Improvement scale and rs1130214 polymorphism was observed. Conclusions: AKT1 gene polymorphism rs1130214 is associated with antidepressant treatment response in patients with depressive disorders.     

认知行为疗法治疗难治性抑郁患者的效果及护理

目的探讨认知行为疗法治疗难治性抑郁患者的效果及护理方法。方法便利抽样法选择2009年10月至2010年9月在丽水市第二人民医院住院的40例符合中国精神障碍分类与诊断标准(第3版)抑郁症诊断标准的患者。按入院先后顺序将患者分为观察组和对照组,每组20例。两组患者均采用5-羟色胺再摄取抑制剂类抗抑郁药物治疗20周以上,并联合一种抗精神病药或情绪稳定剂,5-羟色胺再摄取抑制类抗抑郁药剂量相对保持固定(20～40mg/d)。对照组患者进行常规护理,观察组患者采用认知行为疗法及护理。连续治疗20周,采用汉密尔顿抑郁量表(Hamilton depressive scale-17items,HAMD17)和抑郁自评量表(self-rating depressive scale,SDS)对两组患者进行调查。结果治疗前后,两组患者的HAMD评分的差异有统计学意义(均P<0.05);治疗第10周末、第20周末,两组患者HAMD评分的差异有统计学意义(均P<0.05)。治疗前后,两组患者的SDS评分的差异有统计学意义(均P<0.05);治疗第10周末、第20周末,两组患者SDS评分的差异有统计学意义(均P<0.05)。经治疗20周...     

躯体形式障碍的药物治疗现状

躯体形式障碍是精神科常见的一种神经症,该病具有较高的发病率和很强的专科特点。绝大多数患者到综合医院就诊,但临床识别率和有效治疗率很低,给患者造成极大的经济和心理负担。本文对不同药物治疗躯体形式障碍的疗效及常见不良反应进行了综述,旨在为临床用药提供依据。