氯丙咪嗪血浓度与抑郁症疗效的关系

应用放射配基结合法测定１３例抑郁症病人以固定翼丙咪嗪剂量治疗的血清浓度，并用汉密尔顿抑郁量表、Ｚｕｎｇ抑郁自评量表等评定疗效，精神药物副反应量表评定药物副反应。研究表明，氯丙咪嗪血清浓度与治疗后第３、５、７周疗效呈正相关（Ｐ＜０．０５），与副反应评分无关。稳态浓度在个体之间差异显著，平均为１３４．６８±６５．０５ｎｇ／ｍｌ，最低有效浓度７９．６ｎｇ／ｍｌ，未发现治疗上限。氯丙咪嗪有效率８４．６％，是一种良好的抗抑郁剂。     

国产氯丙咪嗪针剂治疗抑郁症临床观察

本文报告使用国产氯丙咪嗪针剂治疗抑郁症31例的临床疗效。31例抑郁症患者分成三组分别应用静脉滴注,肌肉注射和口服。HDS评分提示临床疗效最佳为静滴组,尤以改善自杀、自罪念头严重的抑郁症患者为佳。常见副作用为口干、便秘,但不影响疗程。作者建议最高注射剂量每日不宜超过100mg。     

氯丙咪嗪血药浓度与疗效的相关研究

目的 :探讨氯丙咪嗪治疗抑郁症的口服剂量、血药浓度与临床疗效之间关系 ,及其有效血浓度范围。　方法 :符合 CCMD- 2诊断标准的抑郁症病人 30例 ,汉密尔顿抑郁量表 (HAMD)评分2 1～ 45分 ,平均 (34.87± 6 .5 3)分 ;纽卡斯尔抑郁诊断量表 (NDI)评分 6～ 10分进入研究。以不定剂量氯丙咪嗪口服治疗 ,共治疗 8周。以 HAMD减分率评定疗效。荧光免疫偏振分析仪 (TDx)测第14天稳态血药浓度。　结果 :氯丙咪嗪剂量 2 5～ 10 0 m g/ d时血浓度范围变异很大 [46～ 44 7ng/ ml,平均 (183± 86 ) ng/ m l];口服剂量与血药浓度呈非线性相关 (P<0 .0 5 ) ;血药浓度与临床疗效显著相关(r=- 0 .5 5 2 ,P=0 .0 0 16 ) ,呈指数曲线关系。　结论 :氯丙咪嗪有效血浓度在 12 6～ 40 0 ng/ ml之间 ,临床长期使用应以血药浓度监测手段指导     

文拉法辛与氯丙咪嗪治疗抑郁症对照研究

对文拉法辛与氯丙咪嗪治疗抑郁症进行对照研究。     

静滴氯丙咪嗪治疗抑郁症—与电休克对照

因三环抗抑郁药需口服治疗剂量一二周后方能起效,难以达到迅速控制病情的效果,故对严重自杀观念和行为、抑郁性木僵及拒绝服药等病情严重的抑郁病人只能首选电休克治疗。然而对伴发热、严重呼吸系统疾病、骨关节病、躯体衰弱或老年病人,电休克又属禁忌。对于此类病员如何治疗,是     

国产氯丙咪嗪注射与片剂治疗抑郁症的对照研究

报告国产氯丙咪嗪注射液和片剂治疗125例抑郁症对照研究,注射组73例,片剂组52例,采用量表和四级标准评定疗效。结果显示,氯丙咪嗪针剂注射组起效早于片剂口服组,治疗2周末抗抑郁疗效优于片剂,各量表减分值大于片剂组。副作用:针剂组与片剂组相似。对氯丙咪嗪注射液临床应用价值进行了讨论。     

氯丙咪嗪及氟西汀治疗强迫症疗效与 5 - 羟色胺含量的动态观察

目的探讨强迫症与５－羟色胺（５－ＨＴ）的关系。方法本文选用氯丙咪嗪和氟西汀治疗３８名强迫症病人,同时观察治疗前后患者血小板５－ＨＴ含量的变化。结果未服药强迫症病人血小板５－ＨＴ含量较正常人高（Ｐ＜０．０１）。经药物治疗后,患者的强迫症状明显好转、血小板５－ＨＴ含量逐渐下降,且治疗后血小板５－ＨＴ含量与Ｙ－ＢＯＣＳ评分下降百分率呈负相关（ｒ＝－０．６２０４,Ｐ＜００１）。结论提示强迫症发病可能与５－ＨＴ异常有关。     

氯丙咪嗪与阿米替林治疗重症抑郁症的疗效观察

为研究氯丙咪嗪的抗抑郁作用,本文应用氯丙咪嗪（湖南洞庭药业股份有限公司生产,批号９８０２２１）与阿米替林（常州四药制药有限公司生产,批号９８０６１２）对照治疗重症抑郁症６６例,现将结果报告于后。１　对象与方法１－１　对象　均符合ＣＣＭＤ—２—Ｒ,抑郁症诊断标准,汉密顿抑郁量表（ＨＡＭＤ）２１项本前１７项评分≥１８分的住院病人,剔除严重躯体疾病者后共６６例,随机分为氯丙咪嗪组和阿米替林组,研究过程中脱失４例,有效病例６２例。氯丙咪嗪组３１例,男１８例,女１３例,年龄（３６±１２）岁,病期（９－１±…     

胞二磷胆碱合并氯丙咪嗪治疗抑郁症对照研究

通过对胞二磷胆碱合并氯丙咪嗪和单用氯丙咪嗪治疗抑郁症５２例的对照研究表明，应用胞二磷胆碱后使前者的奏效时间明显快于后者（Ｐ〈０．０５），而且前者的副反应亦较后者轻，从而克服了氯丙咪嗪奏效慢，抗胆碱能作用强的特点，为抑郁症病人，特别是有自杀观念的病人提供了一条见效快，副反应少的治疗方法，笔者认为此疗法就引起精神科同仁重视并加以推广应用。     

万拉法新与氯丙咪嗪治疗抑郁症的疗效比较

作者采用万拉法新与氯丙咪嗪治疗抑郁症，并对其疗效进行了比较，现报道于后。     

Lithium addition in antidepressant-resistant depression: effects on platelet 5-HT, plasma 5-HT and plasma 5-HIAA concentration

The efficacy of the addition of lithium to an established course of antidepressant treatment can be explained by a synergistic effect of the two drugs on central 5-HT neurotransmission. In the present study we investigated the effect of lithium addition on the 5-HT concentration in plasma and platelets and the concentration of 5-HIAA. Thirty-nine depressed inpatients who fulfilled the DSM-IV criteria for major depressive disorder and who did not respond to monotherapy with either imipramine or fluvoxamine participated in this study. Concentration of 5-HT in both plasma and platelets did not change significantly during lithium addition. The 5-HT ratio (plasma concentration/platelet concentration) shows a small non-significant increase after 3 weeks lithium addition. The mean concentration of 5-HIAA shows a significant increase during lithium addition; with no difference between the imipramine and the fluvoxamine sample. The increments in 5-HIAA concentration during lithium addition are indicative of an increased 5-HT turnover.     

脑卒中后抑郁患者检测SEP与血浆5-羟色胺的临床意义

目的探讨脑卒中后抑郁(post-stroke depression,PSD)患者体感诱发电位(somatosensory evoked potential,SEP)与血浆5-羟色胺(5-hydroxytryptamine,5-HT)水平的变化及其相关性,为脑卒中后抑郁的诊断及预后提供科学依据。方法单纯脑卒中组(n=19)、脑卒中后抑郁组(n=17),采用汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)判断抑郁程度,另设正常对照组(n=12),检测3组体感诱发电位N9、N13、N20的潜伏期及波幅;检测各组血浆5-HT含量,比较分析3组体感诱发电位和血浆5-HT含量。结果脑卒中患者、脑卒中后抑郁患者正中神经测定N20的潜伏期及波幅异常率较正常人高(P0.05);脑卒中后抑郁组血浆中5-HT含量明显低于正常对照组或脑卒中组,差异显著均有统计学意义(P0.05);脑卒中后抑郁患者HAMD评分与N20潜伏期呈正相关、与N20波幅呈负相关,N9波幅、N9潜伏期、N13波幅、N13潜伏期、N20波幅无相关;脑卒中后抑郁组HAMD评分与血浆中5-HT含量呈负相关。结论脑卒中后抑郁患者血浆中5-HT含量明显低于正常人或脑卒中患者,并且脑卒中后抑郁患者及脑卒中患者正中神经测定N20波幅及潜伏期异常率明显高于正常组。因此,检测脑卒中患者的SEP中N20波幅、潜伏期及血浆5-HT水平,将对脑卒中后抑郁的诊断及预后具有很好的临床意义。     

博乐欣治疗抑郁症的疗效及其与血药浓度的关系对照研究

目的　探索博乐欣治疗抑郁症的临床疗效和安全性及与血药浓度的关系。方法　对符合CCMD - 3抑郁症发作诊断标准的 74例抑郁症患者进行博乐欣和百忧解的对照研究 ,其中博乐欣组 34例 ,百忧解组 4 0例。于治疗前及治疗后 1、2、4、6周末采用汉密顿抑郁量表 (HAMD) ,副反应量表 (TESS)评定。采用HPLC测定治疗后的第2、6周末博乐欣血浓度。结果　经 6周治疗后 ,博乐欣组治疗显效率为 82 % ,百忧解组为 75 % ,两组相比较 ,差异无显著性 (P >0 0 5 ) ;第 1周末两组的HAMD减分率比较差异有高度显著性 (P <0 0 1) ;博乐欣组显效时间为 (5 6 8±3 5 5 )天 ,百忧解组为 (12 74± 5 6 3)天 ;并发现博乐欣血浓度早期治疗窗为 10 0～ 30 0ng/mL。结论　博乐欣治疗抑郁症的疗效和副反应与百忧解相当 ,但前者起效更快 ,适合临床快速控制抑郁症状     

5-HT6受体基因多态性与双相情感障碍的关联研究

目的探讨5-HT6受体基因多态性与双相情感障碍之间的关系。方法应用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)技术，对93例双相情感障碍病人和102例正常对照者的5-HTs受体基因多态性(267C／T)进行了检测。结果双相情感障碍与5-HT。受体基因的多态性(267C／T)之间无显著意义的关联，发病年龄也与此多态性无关。结论5-HT。受体基因的267C／T多态性可能与双相情感障碍的发生无直接关联。     

Pre- and post-synaptic effects of the 5-HT3 agonist 2-Methyl-5-HT on the 5-HT system in the rat brain

Microiontophoretic applications of 5-HT and of the 5-HT₃ agonist 2-methyl-5-HT produced a current-dependent suppression of firing activity of both hippocampal (CA₁ and CA₃) and cortical neurons in anesthetized rats. Concomitant microiontophoretic applications of the 5-HT₃ antagonists BRL 46470A and S-zacopride, as well as their intravenous injection, did not antagonize the inhibitory effect of 5-HT and 2-methyl-5-HT. In contrast, the 5-HT_1A antagonist BMY 7378, applied by microiontophoresis or administered intravenously, significantly reduced the inhibitory action of 5-HT and 2-methyl-5-HT. The firing activity of dorsal raphe 5-HT neurons was also reduced by 5-HT, 2-methyl-5-HT and the 5-HT_1A agonist 8-OH-DPAT applied by microiontophoresis. While BRL 46470A (0.1 and 1 mg/kg, i.v.) did not antagonize the inhibitory effect of the three 5-HT agonists on 5-HT neuronal firing activity, only that of 8-OH-DPAT was attenuated by the 5-HT_1A antagonist (+) WAY 100135. R-zacopride significantly reduced the duration of suppression of firing activity of CA₃ pyramidal neurons induced by the electrical stimulation of the ascending 5-HT pathway, and this reducing effect was prevented by the three 5-HT₃/5-HT₄ antagonists renzapride, S-zacopride and tropisetron, but not by BRL 46470A. Finally, in in vitro superfusion experiments, both BRL 46470A and S-zacopride antagonized the enhancing action of 2-methyld-HT on the electrically-evoked release of [³H]-5-HT in both rat frontal cortex and hippocampus slices. These findings suggest that, in vivo, the suppressant effect of 2-methyl-5-HT on the firing activity of dorsal hippocampus pyramidal, somatosensory cortical, and dorsal raphe 5-HT neurons is not mediated by 5-HT₃ receptors, but rather by 5-HT_1A receptors. The attenuating effect of R-zacopride on the effectiveness of the stimulation of the ascending 5-HT pathway is not mediated by 5-HT₃ receptors. In contrast, in vitro, the enhancing action of 2-methyl-5-HT on the electrically-evoked release of [³H]5-HT in both frontal cortex and hippocampus slices is mediated by 5-HT₃ receptors. © 1995 Wiley-Liss, Inc.     

Spinal cord injury-specific depression of monosynaptic spinal reflex transmission by l-5-hydroxytryptophan results from loss of the 5-HT uptake system and not 5-HT receptor supersensitivity

We studied changes in the spinal segmental reflex and serotonergic (5-HT) responses in rats after spinal cord injury (SCI) produced by the weight-dropping method at the T8 level. The spinal monosynaptic reflex amplitude (MSR) was recorded from the L5 ventral root following stimulation of the ipsilateral L5 dorsal root. The 5-HT precursor l-5-hydroxytryptophan (L-5-HTP) depressed MSR in the spinal cord injured rats but not in normal rats. We investigated whether the SCI-specific depression of MSR by L-5-HTP was attributable to postsynaptic supersensitivity of 5-HT receptors or presynaptic loss of the 5-HT uptake system. Sumatriptan, a selective 5-HT(1B/1D) receptor agonist that is not taken up by 5-HT transporters, depressed the MSR similarly in both SCI and normal rats, suggesting that SCI resulted in the loss of 5-HT terminals and not postsynaptic supersensitivity of 5-HT receptors.     

Ex vivo inhibitory effect of the 5-HT uptake blocker citalopram on 5-HT synthesis

Summary Serotonin (5-hydroxytryptamine, 5-HT) synthesis was determined in vivo by measuring the accumulation of 5-hydroxytryptophan (5-HTP) in rat frontal cortex after inhibition of aromatic amino acid decarboxylase by administration of m-hydroxybenzylhydrazine (NSD 1015) (100 mg/kg, i.p.). The selective 5-HT reuptake inhibitor, citalopram, the 5-HT_1a agonists, (±)8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), ipsapirone, gepirone and the 5-HT_1a/b agonist, 7-trifluoromethyl-4(4-methyl-1-piperazinylpyrolo[1,2-a]-quinoxaline (CGS 12066B), the 5-HT_1a/b ligands and -adrenoceptor antagonists, (±)pindolol and (±)alprenolol, and the non-selective 5-HT ligands, m-chlorophenylpiperazine (mCPP) and metergoline, all inhibited the synthesis of 5-HT. The 5-HT_1a /5-HT₂ antagonist, spiperone, alone, had no effect on basal 5-HT synthesis, however it attenuated the effect of 8-OH-DPAT by 56% and CGS 12066B by 39% but only barely that of citalopram by 17%. The selective 5-HT_1a antagonist, WAY 100635, which did not modify by itself 5-HT synthesis, had no effect on citalopram-induced reduction of 5-HT synthesis. Neither the 5-HT₂ agonist, (±)1-(2,5-dimethoxy-4-indophenyl)-2-aminopropane (DOI) nor the 5-HT₂ antagonist, ritanserin, had any effect on the synthesis of 5-HT. In addition, ritanserin did not modify the inhibitory effect of citalopram. Methiothepin was the only compound to increase 5-HT synthesis. These results suggest that the effect of citalopram on the synthesis of 5-HT is not mediated by 5-HT_1a or 5-HT₂ receptors and that other receptors may be involved.     

Adaption of the serotoninergic neuronal phenotype in the absence of 5-HT autoreceptors or the 5-HT transporter: involvement of BDNF and cAMP

Serotonin 5-HT1A and 5-HT1B receptors and the 5-HT transporter are key regulators of the serotoninergic neuronal phenotype. We show here that genetic deletion of any of these elements differentially regulates 5-HT neuronal number in rostral raphe cultures from E14 mice. Serotonin neuronal number was increased by almost four-fold and 1.8-fold in cultures from 5-HT1AR-/- and 5-HT1BR-/- mice, respectively. In contrast, the lack of serotonin transporter expression was associated with a 50% decrease in 5-HT neuronal number. In raphe cultures from the rat, BDNF and cAMP have been shown to up-regulate the neuronal serotoninergic phenotype through TrkB-dependent mechanisms [Rumajogee et al. (2002) J. Neurochem., 83, 1525-1528]. Similar tyrosine kinase-dependent up-regulating effects, in the absence of serotoninergic key-elements are reported here, on both 5-HT neuronal number and neurites length. However, the extents of BDNF-triggered and cAMP-triggered effects on serotoninergic neuritic length were approximately 1.5-fold higher in 5-HT1AR-/- mutants. These findings show that the up-regulatory mechanisms triggered by BDNF on serotoninergic neuronal number and neurite extension are different and that the latter are partially linked to 5-HT, probably through 5-HT1A autoreceptors. Together, these data suggest that serotonin autoreceptors, mainly 5-HT1A but also 5-HT1B, may be responsible for a tonic auto-inhibitory effect of 5-HT itself on the serotoninergic neuronal phenotype during embryonic development, particularly marked in the absence of the 5-HT transporter.     

Electrophysiological evidence for a functional interaction between 5-HT1A and 5-HT2A receptors in the rat medial prefrontal cortex: An lontophoretic study

In this study, we examined the interaction of 5-HT_1A and 5-HT_2A receptors in the rat medial prefrontal cortex (mPFc) using the techniques of extracellular single unit recording and microiontophoresis. The iontophoresis of the selective 5-HT_1A receptor agonist (±)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) produced a current-dependent suppression (2.5-20 nA) of the basal firing rate of spontaneously active mPFc cells. The iontophoretic (5-10 nA) and systemic administration (0.1-0.5 mg/kg, i.v. ) of the 5-HT_2A/5-HT_2C receptor antagonist ritanserin and the selective 5 HT_2A receptor antagonist MDL 28727 significantly potentiated and prolonged 8-OHDPATs suppressant action. In addition, the systemic administration of another selective 5-HT_2A antagonist MDL 100907, but not its less active enantiomer MDL 100009, also potentiated and prolonged 8-OHDPATs action. The potentiating effect of the 5-HT_2A receptor antagonists on the action of 8-OHDPAT is specific in that neither the iontophoresis of ritanserin nor MDL 28727 altered the suppressant action produced by the iontophoresis of the 5-HT₃ receptor agonist 2-methylserotonin onto mPFc cells. Moreover, the suppressant action of 8-OHDPAT was not altered by the systemic administration of the selective 5-HT₃ receptor antagonist granisetron (0.1-0.5 mg/kg, i.v.). On the other hand, the iontophoresis of a low current (0.5 nA) of the 5-HT_2A,2C receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) potentiated the excitation induced by the iontophoresis of 1-glutamate on quiescent mPFc cells. The iontophoresis of 8-OHD-PAT at a current that had no effect on the firing rate of 1-glutamate activated when administered alone significantly attenuated the excitatory action produced by the iontophoresis of DOI. Overall these results confirm and extend the hypothesis that there is an interaction between 5-HT_1A and 5-HT_2A receptors in the mPFc at the neuronal level. © 1994 Wiley-Liss, Inc.     

5-HT2A受体基因多态性与单相抑郁及其自杀行为的关系

目的探讨中国汉族人群中单相抑郁患者及其自杀行为与5-HT2A受体基因T102C多态性的关系。方法采用PCR—RFLP方法,检测281例单相抑郁患者组和219名对照组5- HT2AT102C基因型及等位基因频率,分析患者组和对照组之间以及患者组内有无自杀行为之间该基因型及等位基因的差异。结果患者组中5-HT2AT102C基因型和等位基因与对照组相比,差异未见显著性,但患者组内有自杀行为的个体携带C 的基因型(A1/A2和A2/A2)的明显高于C-(A1/A1)基因型,差异有统计学意义(P＜0．05)。结论本研究提示,5-HT2AT102C基因多态性与单相抑郁症的自杀行为有关,C等位基因可能是单相抑郁症患者中有自杀行为的风险因子之一。