拉莫三嗪联合抗抑郁药物治疗双相抑郁的研究:国内文献Meta分析

目的评价拉莫三嗪联合抗抑郁药物与单一使用抗抑郁药物治疗双相抑郁症的疗效与安全性。方法应用循证医学方法对符合标准的5项研究进行分析,评价拉莫三嗪联合抗抑郁药物与单一使用抗抑郁药物治疗双相抑郁的有效率、症状学变化以及转相率的差异。结果拉莫三嗪联合抗抑郁药物与单一使用抗抑郁药物相比,症状改善更为明显(WMD=-1.81,95%CI:-2.64~-1.71,Z=5.52,P0.01),有效率较高(59/109 vs.35/106,OR=2.43,95%CI:1.38~4.27,Z=3.08,P0.01),而且也显著降低了联合组的转相率(7/86vs.21/85,OR=0.26,95%CI=0.10-0.66,Z=2.86,P0.01)。结论拉莫三嗪联合抗抑郁药物不仅可以增加治疗效应,而且也降低了转相风险。     

不同类型抗抑郁剂在双相抑郁治疗中导致转相的回顾性研究

目的比较不同抗抑郁剂在双相抑郁治疗过程中转相率的差异。方法对150例接受抗抑郁剂治疗的双相抑郁患者出现躁狂、轻躁狂、快速循环情况进行调查，并比较不同抗抑郁剂之间的差异。结果150例双相抑郁中，共有41例患者在治疗过程中转相，总发生率（转相率）34％。其中使用双重作用抗抑郁剂（DAA）患者的转相率为29．2％，使用选择性5-羟色胺回吸收抑制剂〈SSRI）的患者为12.7％，DAA与SSRI联合应用者为48．7％，三组间差异有统计学意义（Χ^2=11．87，P〈0．001）。DDA与SSRI联合应用者转相率高于SSRI，差异有统计学意义（Χ^2=16．06，P〈0．001，危险比OR=6．53）；DAA转相率高于SSRI。差异有统计学意义（Χ^2=4.65，P〈0．01，OR=6．53）；DAA与SSRI联合应用者转相率高于DAA（Χ^2=3．49，P〉0.05，OR=2．31）。转相与未转相者相比，心境稳定剂的应用差异有统计学意义（7／41，52／109，Χ^2=11．72，P〈0．001）。结论不同类型抗抑郁荆在双相抑郁治疗中引起的转相率有差异，其中联合使用抗抑郁剂的转相率最高，而心境稳定剂的联合应用有助于预防转相。     

不同类别抗抑郁药物的转躁率比较

目的调查不同类型抗抑郁药物治疗抑郁发作过程中出现转躁的发生率。方法对675例接受各种抗抑郁药物治疗的抑郁发作患者出现躁狂发作的情况进行回顾性调查,比较不同类别抗抑郁药物的转躁率。结果共有97例患者在治疗过程中转躁,总转躁率为14.4%(97/675);单一服用选择性5-羟色胺回收抑制剂(SSRI)抑郁患者转躁率9.1%(36/396),单一服用5-羟色胺与去甲肾上腺素回收抑制剂(SNRI)文拉法辛的抑郁患者中转躁率22.8%(24/105),单一服用去甲肾上腺素与特异性5-羟色胺能抗抑郁药物(NaSSA)米氮平的患者转躁率14.6%(6/41),单一服用三环抗抑郁药物(TCA)者转躁率27.2%(18/66)。以上组别转躁率差异具有统计学意义(2=34.42,P<0.01),而SSRI分别与SNRI、TCA之间的差异均达到统计学意义(2=11.99,P<0.01;2=18.1,P<0.01)。任何两种抗抑郁药物联合应用者转躁率36%(9/25),一种抗抑郁药物联合一种心境稳定剂者转躁率9.3%(4/43)。女性患者转躁率高于男性患者,差异具有统计学意义(16.8%vs11.1%,2=4.62,P<0.05)。结论抗抑郁药物治疗过中,一部分患者会出现转躁,尤以服用具有双重作用机制的药物为甚。     

抗抑郁药物与转躁

<正>心境障碍转为轻躁狂、躁狂或混合发作状态与抗抑郁药物的关系一直是一个特别有争议的话题。为了明确"抗抑郁药物相关的心境障碍"的术语,国际双相障碍协会(ISBD)一直推荐使用"治疗性急性心境转换"来取代"抗抑郁药物导致的转相"。ISBD关于"治疗性急性心境转换"的定义提供了操作性诊断标准,在将转相抗抑郁药物的使用之前,需要充分考虑到时间、病程、严重性等因素[1],但是无论如何,这种病理现象的存在与抗抑郁药物不无关系,无     

双相障碍抑郁发作药物治疗的研究进展

以抑郁为首发的双相障碍患者往往进行抗抑郁治疗,很少联合应用心境稳定剂[1],致使很多患者转躁.重性抑郁障碍(MDD)和双相障碍在最新的DSM-5中是两种并列的主要心境障碍,近年来随着新的抗抑郁药不断出现,使大家对MDD的关注相对较多,国外有资料显示,双相障碍被误诊为单相抑郁多达40%,平均延误诊断7.5年,约1/3患者因为未使用心境稳定剂而影响疗效.MDD和双相障碍抑郁发作是两种完全不同的疾病,后者的临床表现和病程变化更为复杂,增加了治疗的难度,预后效果更差,抗抑郁治疗易转相,故而有效治疗双相障碍抑郁发作受到越来越多的关注[2].本文对双相障碍抑郁发作药物治疗的新发展进行综述如下.     

抗抑郁剂联合心境稳定剂治疗双相障碍患者:1年随访

目的:观察抗抑郁剂联合心境稳定剂治疗双相障碍1年的结局,并评价不同疗效对双相抑郁结局的影响。方法:选择符合ICD-10双相障碍诊断标准患者,急性期进行8周抗抑郁剂和心境稳定剂联合治疗,痊愈和有效者进入1年维持治疗期。用24项汉密顿抑郁量表(HAMD)、Bech-Rafaelsen躁狂量表(BRMS)和临床疗效总评量表(CGI)评定疾病严重程度和疗效。结果:76例患者急性期治疗痊愈者53例,有效者23例。随访1年后,共43例(56.57%)维持痊愈,17例症状复发,总复发率22.36%。痊愈组36例(67.92%)仍保持痊愈,有效组7例(30.43%)达痊愈,两组差异有显著性(χ2=9.176,P=0.002)。痊愈组抑郁复发率低于有效组(3.77%vs.17.39%,χ2=4.091,P=0.045),两组转躁率差异无统计学意义(11.32%vs.21.74%;χ2=1.406,P=0.236)。生存分析显示痊愈组平均复发时间显著长于有效组[(10.06±2.14)个月vs.(9.00±3.67)个月;u=9.327,P=0.002]。结论:抗抑郁剂联合心境稳定剂治疗双相障碍抑郁发作患者1年后复发率低,急性期治疗痊愈者优于非痊愈者。     

单相与双相抑郁障碍患者临床特征的对照研究

目的比较单相与双相抑郁障碍患者的临床特征,为单相和双相抑郁障碍的鉴别诊断提供参考。方法连续入组2012年6月-2013年11月在广州医科大学附属脑科医院住院、符合《国际疾病分类(第10版)》(ICD-10)诊断标准的单相抑郁障碍(单相组,n=72)和双相抑郁障碍(双相组,n=64)患者,收集并分析两组一般人口学资料和临床特征,采用汉密尔顿抑郁量表17项版(HAMD-17)评定抑郁症状。结果单相组女性及已婚患者比例均高于双相组(χ2=18.74、4.68,P0.05或0.01);双相组平均起病年龄小于单相组(t=-2.13,P=0.035);双相组性格外向者比例高于单相组(χ2=9.74,P=0.002);单相组有病前诱因者比例高于双相组(χ2=18.96,P0.01);双相组伴不典型抑郁症状者比例高于单相组(χ2=24.60,P0.01);双相组既往抑郁发作次数多于单相组(Z=-5.37,P0.01);单相组HAMD-17总评分及躯体化焦虑和食欲减退因子评分均高于双相组,差异均有统计学意义(t=-2.78~-2.06,P0.05或0.01)。结论单相与双相抑郁障碍患者在性别、婚姻状况、发病年龄、是否有病前诱因、是否伴不典型抑郁症状、既往发作次数及HAMD-17评分方面存在差异。     

抗抑郁药引发抑郁发作患者转相的观察

我们对接受了3个月抗抑郁治疗的抑郁发作患者进行转相调查,报道如下. 对象 190例,均为调查者所在的12所医院2005年1月1日至2007年12月31日的门诊或住院患者,均符合中国精神疾病分类与诊断标准第3版的抑郁发作或双相抑郁诊断标准.其中男6l例,女129例;年龄16～62岁,平均(26±20)岁;抑郁症170例,双相抑郁20例;有阳性心境障碍家族史者38例,无家族史者152例.     

抗抑郁药引发抑郁发作患者转相的观察

我们对接受了3个月抗抑郁治疗的抑郁发作患者进行转相调查,报道如下. 对象 190例,均为调查者所在的12所医院2005年1月1日至2007年12月31日的门诊或住院患者,均符合中国精神疾病分类与诊断标准第3版的抑郁发作或双相抑郁诊断标准.其中男6l例,女129例;年龄16～62岁,平均(26±20)岁;抑郁症170例,双相抑郁20例;有阳性心境障碍家族史者38例,无家族史者152例.     

抗抑郁药引发抑郁发作患者转相的观察

我们对接受了3个月抗抑郁治疗的抑郁发作患者进行转相调查,报道如下. 对象 190例,均为调查者所在的12所医院2005年1月1日至2007年12月31日的门诊或住院患者,均符合中国精神疾病分类与诊断标准第3版的抑郁发作或双相抑郁诊断标准.其中男6l例,女129例;年龄16～62岁,平均(26±20)岁;抑郁症170例,双相抑郁20例;有阳性心境障碍家族史者38例,无家族史者152例.     

视频脑电图在小儿癫痫诊断中的应用

目的评价视频脑电图(video-EEG)在小儿癫诊断中的应用价值。方法对126例具有发作性症状的患儿进行连续8h的包括清醒、睡眠、诱发试验及必要的认知测验的视频脑电图监测。结果经发作期视频脑电图证实,39例初诊为癫性发作的患儿中14例(35%)为非癫性发作;15例其他症状发作中13例(86%)为非癫性发作。64例样放电患儿中51例(80%)确定发作类型,22例(34%)确定癫类型。视频脑电图可发现短暂轻微的癫发作及样放电引起的一过性认知损伤。结论视频脑电图在排除非癫性发作、确定癫性发作的类型、评价脑电-临床关系方面可提供准确可靠的证据,进一步提高癫的临床诊断水平。     

Role of glutathione in repair of free radical damage in hippocampus in vitro.

Depletion of glutathione (GSH), an intrinsic antioxidant, increases vulnerability to free radical damage in a number of cell systems. This study investigates the role of GSH in limiting electrophysiological damage and/or recovery from free radical exposure in slices of guinea pig hippocampus. Synaptic potentials (PSPs) and population spikes (PSs) were recorded from field CA1. Free radicals were generated from 0.006% peroxide through the Fenton reaction. Analysis of the input-output curves showed that peroxide treatment decreased PSPs and impaired ability of the PSPs to generate PSs as previously reported. Recovery was nearly total within a half hour. Treatment with 5 mM buthionine sulfoximine (BSO) for 2 h depleted hippocampal GSH to 79.2% of control values. The extent of free radical damage was not increased. Recovery, however, was only partial. GSH was further depleted by oxidation with diamide or covalent bonding with dimethyl fumarate (DMF) immediately before and during the peroxide treatment. Neither diamide nor DMF treatment in BSO-incubated tissue enhanced peroxide-induced electrophysiological deficits. Following these treatments, however, tissue showed little recovery from free radical damage. We conclude that glutathione is essential for repair processes in hippocampal neurons exposed to oxidative damage.     

Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity

The pathogenesis of stroke, trauma and chronic degenerative diseases, such as Alzheimer's disease (AD), has been linked to excitotoxic processes due to inappropriate stimulation of the N-methyl-D-aspartate receptor (NMDA-R). Attempts to use potent competitive NMDA-R antagonists as neuroprotectants have shown serious side-effects in patients. As an alternative approach, we were interested in the anti-excitotoxic properties of memantine, a well-tolerated low affinity uncompetitive NMDA-R antagonist presently used as an anti-dementia agent. We explored in a series of models of increasing complexity, whether this voltage-dependent channel blocker had neuroprotective properties at clinically relevant concentrations. As expected, memantine protected neurons in organotypic hippocampal slices or dissociated cultures from direct NMDA-induced excitotoxicity. However, low concentrations of memantine were also effective in neuronal (cortical neurons and cerebellar granule cells) stress models dependent on endogenous glutamate stimulation and mitochondrial stress, i.e. exposure to hypoxia, the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) or a nitric oxide (NO) donor. Furthermore, memantine reduced lethality and brain damage in vivo in a model of neonatal hypoxia-ischemia (HI). Finally, we investigated functional rescue (neuronal capacity to migrate along radial glia) by memantine in cerebellar microexplant cultures exposed to the indirect excitotoxin 3-nitropropionic acid (3-NP). Potent NMDA-R antagonists, such as (+)MK-801, are known to block neuronal migration in microexplant cultures. Interestingly, memantine significantly restored the number of neurons able to migrate out of the stressed microexplants. These findings suggest that inhibition of the NMDA-R by memantine is sufficient to block excitotoxicity, while still allowing some degree of signalling.     

Storage of lipofuscin in neurons in mucopolysaccharidosis

Summary A histochemical and ultrastructural study was made on the brain of a 23-year-old man with Sanfilippo's syndrome. In accordance with previous reports the cortical nerve cells contained a PAS-positive lipid storage substance. This showed intense autofluorescence in UV-light and was positive with various stains for lipofuscin. The storage material appeared ultrastructurally as inclusion bodies composed of short lamellated membranes, granular material, and vacuoles. In addition, concentrically and transversely lamellated membranous cytoplasmic bodies were observed in the nerve cells. It is concluded that the PAS-positive lipid storage material in the neurons was composed partly of lipofuscin in addition to other lipids presumably glycosphingolipids.Supported by a grant from the Expressen Prenatal Research Foundation     

Role of vincristine in the inhibition of angiogenesis in glioblastoma

Objective: Vincristine, a microtubule-destabilizing drug, was found to exhibit anti-angiogenic effects and anti-tumoral activity. However, the precise mechanism by which vincristine inhibits angiogenesis in glioblastomas is not well understood. Our aim was to investigate whether vincristine affects vascular endothelial growth factor (VEGF) expression in glioblastoma cells and determine whether it is mediated by the downregulation of hypoxia-inducible factor-1α (HIF-1α).

Methods: We investigated the expression of HIF-1α in glioblastoma tissues resected from patients and in human glioblastoma cell lines using immunohistochemistry, Western blot analysis, and immunocytochemistry. In addition to an MTT assay assessing the effect of vincristine on cell proliferation and viability, the effects of vincristine on VEGF mRNA expression and HIF-1α protein were examined using real-time RT-PCR and Western blot analysis under 1% O₂ (hypoxia).

Results: HIF-1α was expressed in the majority of glioblastoma tissues and was detected mainly in the nucleus. Strong immunoreactivity for HIF- 1 α was found often in the hypercellular zones. Under hypoxic conditions, HIF-1α protein levels in the glioblastoma cell lines increased, primarily localizing into the nucleus similar to glioblastoma tissues. Exposure of glioblastoma cells to vincristine resulted in enrichment of the G₂-M fraction of the cell cycle, which suggests that vincristine-mediated growth inhibition of glioblastoma is correlated with mitotic inhibition. Using doses lower than those found to reduce the viability and proliferation of cells by 50% (IC₅₀), vincristine decreased both the expression of VEGF mRNA and the level of HIF-1α protein in hypoxic glioblastoma cells. In addition, following exposure to vincristine, the expression of VEGF mRNA was correlated with HIF-1α protein levels.

Conclusions: Our results suggest that the mechanism by which vincristine elicits an anti-angiogenic effect in glioblastomas under hypoxic conditions might be mediated, in part, by HIF-1α inhibition.