抗抑郁药物是如何帮助患者的?

正抗抑郁药物可以有助于缓解失眠、食欲不振以及疲劳相关的抑郁症。当医生建议患者服用抗抑郁药物以治疗抑郁症,如选择性5-羟色胺再摄取抑制剂(SSRIs)或者是5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRIs),这不仅是促进改善情绪。抑郁症有很多潜在的身体作用。哈佛附属马萨诸塞州综合医院老年病学专家阿曼达·赫南德兹博士称,大部分人都     

文拉法辛缓释片与匹维溴铵治疗无明显情绪障碍腹泻型肠易激综合征的初步研究

背景：目前对选择性5-羟色胺再摄取抑制剂（SSRIs）可用于治疗伴抑郁或焦虑状态的肠易激综合征（IBS）已基本达成共识,但关于SSRIs治疗无明显情绪障碍IBS的研究相对较少。目的：评价5-羟色胺去甲肾上腺素再摄取抑制剂文拉法辛缓释片与匹维溴铵对无明显情绪障碍、长期反复发作腹泻型IBS（IBS—D）的治疗作用。方法：本临床研究协作组前期关于文拉法辛缓释片与匹维溴铵治疗IBS．D的随机对照多中心研究中,376例患者完成观察。23例经汉密尔顿抑郁量表（HAMD）和汉密尔顿焦虑量表（HAMA）评价为无明显抑郁、焦虑状态者中,对照组7例（口服匹维溴铵8周）,试验组16例（口服文拉法辛缓释片与匹维溴铵8周）。比较两组患者的症状评分和HAMD、HAMA评分以及总有效率。结果：服药1周后起,试验组腹痛、腹泻评分和症状总评分均显著低于对照组（P〈0．05）;服药4周后起,试验组HAMD、HAMA评分亦显著低于对照组（P〈0．05）。试验组总体症状改善的总有效率显著高于对照组（87．5％对28．6％,P〈0．05）。结论：文拉法辛缓释片与匹维溴铵可改善无明显情绪障碍IBS-D患者的核心症状和不良情绪因子,疗效明显优于单用匹维溴铵。     

盐酸氟西汀治疗老年功能性消化不良的疗效观察

目的 探讨抗抑郁药盐酸氟西汀（百忧解）对功能性消化不良（FD）的老年患者的疗效。方法 选取25例证实为FD的老年患者给予抗抑郁药，5－羟色胺（5－HT）再摄取抑制剂（SSRI）百忧解治疗，疗程均为2月。观察治疗前后腹痛、腹胀、恶心、呕吐、早饱等消化道症状变化。并给予SCL－90量表评价治疗前后患者的精神变化。结果 老年FD患者接受抗抑郁药治疗2月后，前后评分对比，患者的躯体及精神症状均明显改善，P＜0．01。结论 老年FD患者经抗抑郁药治疗可改善患者的躯体和精神两方面的症状。     

难治性肠易激综合征患者的情绪障碍和治疗

背景:肠易激综合征(IBS)是目前最常见的功能性胃肠道疾病之一,然而其病因和发病机制至今尚不太清楚,临床治疗效果亦不十分理想。目的:探讨心理因素在难治性IBS发病中的作用和抗抑郁药对IBS的疗效。方法:分别对36例经常规治疗无效的腹泻型IBS患者和22名健康成人进行汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)和症状自评量表(SCL)鄄90评分以了解其心理状态,并对IBS患者的主要症状(腹部不适、疼痛和排便异常等)进行分级。在常规治疗的基础上随机予IBS患者选择性5鄄羟色胺再摄取抑制剂(SSRI)类抗抑郁药治疗,20例患者使用盐酸帕罗西汀,16例患者使用盐酸氟西汀,疗程均为12周。疗程结束后1周再进行上述量表评分和主要症状分级。结果:除精神病性因子分外,IBS患者HAMD、HAMA和SCL鄄90的总分和各因子分均显著高于健康对照组(P<0.001);接受抗抑郁药治疗12周后,各量表评分均显著低于治疗前(P<0.001或P<0.01),主要症状分级亦明显降低,按意图治疗(ITT)和方案(PP)分析,治愈率分别为47.2%和51.5%,总有效率分别为91.7%和100%。 结论:心理因素在IBS的发病中起重要作用。难治性IBS患者普遍存在抑郁、焦虑等情绪障碍,应用抗抑郁药治疗能显著改善IBS患者躯体和精神两方面的症状。     

5-羟色胺转运体基因多态性与肠易激综合征

肠易激综合征(IBS)是临床最常见的功能性肠病,其病因及发病机制还不完全清楚。5-羟色胺(5-HT)是参与调节胃肠道运动和分泌功能的重要神经递质,在IBS的发病中有重要意义。5-羟色胺转运体(SERT或5-HTT)蛋白再摄取神经突触间隙的5-HT,对其起灭活作用。大量研究表明,SERT基因多态性与IBS各型间可能存在联系。     

新一代抗抑郁症药物治疗

三环类抗抑郁药（ＴＣＡ）虽疗效确凿，但仍有２０％～３０％无效，而且毒副反应较多。病人对药物的耐受性差，过量易引起中毒甚至死亡。从７０年代起，第一代的抗抑郁药选择性５羟色胺（５ＨＴ）再摄取抑制剂（ＳＳＲＩ）。开始了研制，结构与三环类迥然不同，药理作...     

氟西汀治疗脑卒中后抑郁42例疗效观察

脑卒中后抑郁（PSD）是脑卒中患者的常见并发症,占脑卒中患者的25％-79％。氟西汀是选择性5-羟色胺（5-HT）再摄取抑制剂（SSRI）,能有效抑制神经元从突触间隙中摄取5-HT,改善患者的情感状态。2006年5月～2008年10月,我们采用氟西汀治疗PSD患者42例,并与采用多塞平治疗者进行比较。现报告如下。     

米氮平治疗功能性消化不良疗效评价

目的 已有使用抗抑郁药治疗功能性消化不良(FD)合并心理障碍的报道,本研究总结评价去甲肾上腺素和5-羟色胺再摄取抑制剂米氮平治疗FD的疗效及安全性.方法 收集北京协和医院消化内科2009年6月～2010年6月接受米氮平治疗的FD患者资料,随诊内容包括消化不良症状、食欲和体重、精神心理状态和睡眠情况等.总结分析米氮平的疗...     

5-羟色胺转运体与肠易激综合征

肠易激综合征(IBS)是临床最常见的功能性肠病,病因尚不清楚。5-羟色胺(5-HT)是脑-肠轴中的关键递质,它在胃肠运动和感觉,以及中枢情感调节中有重要意义。5-羟色胺转运体(SERT)是一种对5-HT有高度亲和力的跨膜转运蛋白,可将效应部位的5-HT迅速再摄取。大量的证据表明,SERT在IBS的发生和发展中发挥重要的作用。     

逆转由5-羟色胺伴发的性快感缺失

问:性功能不足可伴发于采用环杂类抗抑郁药时,并能用氯化乌拉胆碱或溴化新斯的明等胆碱能制剂来治疗,5-羟色胺再摄取阻滞剂——盐酸氟苯氧丙胺(fluoxetine hydrochloride)亦会对男女病人性欲有损害。应采用何药来对抗此药所致的性功能不足呢?答:氟苯氧丙胺是一种强力5-羟色胺再摄取阻滞剂。对再摄取其它单胺类影响甚少。有报告本     

Impact of psychological stress on irritable bowel syndrome

Psychological stress is an important factor for the development of irritable bowel syndrome (IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stress-sensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.     

The serotonin signaling system: from basic understanding to drug development for functional GI disorders

Serotonin is an important gastrointestinal signaling molecule. It is a paracrine messenger utilized by enterochromaffin (EC) cells, which function as sensory transducers. Serotonin activates intrinsic and extrinsic primary afferent neurons to, respectively, initiate peristaltic and secretory reflexes and to transmit information to the central nervous system. Serotonin is also a neurotransmitter utilized by a system of long descending myenteric interneurons. Serotonin is synthesized through the actions of 2 different tryptophan hydroxylases, TpH1 and TpH2, which are found, respectively, in EC cells and neurons. Serotonin is inactivated by the serotonin reuptake transporter (SERT)-mediated uptake into enterocytes or neurons. The presence of many serotonin receptor subtypes enables selective drugs to be designed to therapeutically modulate gastrointestinal motility, secretion, and sensation. Current examples include tegaserod, a 5-HT(4) partial agonist, which has been approved for treatment of irritable bowel syndrome (IBS) with constipation in women and for chronic constipation in men and women. The 5-HT(3) antagonists, granisetron and ondansetron, are useful in combating the nausea associated with cancer chemotherapy, and alosetron is employed in the treatment of IBS with diarrhea. Serotonergic signaling abnormalities have also been putatively implicated in the pathogenesis of functional bowel diseases. Other compounds, for which efficacy has not been rigorously established, but which may have value, include tricyclic antidepressants and serotonin selective reuptake inhibitors to combat IBS, and 5-HT(1) agonists, which enhance gastric accommodation, to treat functional dyspepsia. The initial success encountered with serotonergic agents holds promise for newer and more potent insights and therapies of brain-gut disorders.     

Antidepressants in IBS: are we deluding ourselves?

The benefit of selective serotonin reuptake inhibitors (SSRIs) in the irritable bowel syndrome (IBS) has not been clear. In the latest randomized trial published this month in the Journal, paroxetine was superior to placebo in terms of improving well-being, but not abdominal pain or bloating. Based on the results of the most recent studies, both tricyclic antidepressants and SSRIs may improve patient satisfaction or quality-of-life without relieving most of the primary gastrointestinal symptoms. This suggests that antidepressant therapy represents at best only a "band-aid" approach to management. Optimizing the use of antidepressants in IBS is a challenge, and these issues are explored in this Editorial.     

Pharmacotherapy: non-serotonergic mechanisms

Antidepressants rapidly relieve pain in irritable bowel syndrome (IBS) and are effective at low doses. Noradrenaline reuptake inhibitors appear to be more effective than selective serotonergic reuptake inhibitors, suggesting that pathways other than those modulated by serotonin may be involved in visceral sensation. Visceral sensitivity is reduced by both centrally and peripherally acting opioids, suggesting the possible existence of an endogenous opioid deficiency in patients with IBS. The alpha(2) adrenoceptor antagonist clonidine, as well as somatostatin, oxytocin, and possibly amitriptyline have also been shown to act as visceral analgesics. As knowledge increases, there are undoubtedly many other possible targets, and new drugs currently undergoing development may provide future benefit in patients with IBS.     

Cardiovascular side effects of newer antidepressants.

We review the cardiovascular effects of newer antidepressants. Although further studies are warranted, the safety of the selective serotonin reuptake inhibitors and the serotonin norepinephrine reuptake inhibitors on patients with comorbid cardiac conditions is impressive. Newer antidepressants should be considered as first-line agents for the treatment of depression in patients with and without cardiovascular disease.     

Challenges to the therapeutic pipeline for irritable bowel syndrome: end points and regulatory hurdles

Recent advances in our understanding of basic neuroenteric mechanisms and the role of effectors and transmitters in the brain-gut axis have provided opportunities to develop new therapeutic agents for irritable bowel syndrome (IBS). Furthermore, human pharmacodynamic studies utilizing transit, colonic, or rectal sensitivity and brain imaging have been useful in determining therapeutic efficacy (particularly for drugs that act on motor function). This review provides an overview of medications that have not yet been approved for treatment of patients with IBS yet have shown promise in phase IIB trials. These include drugs that act on the serotonin receptor and transporter system: antidepressants, norepinephrine reuptake inhibitors, opioids, cholecystokinin antagonists, neurokinin-antagonists, chloride channel activators, guanylate cyclase C agonists, atypical benzodiazepines, probiotics, and antibiotics. The changing landscape in the regulatory approval process has impacted the development of IBS drugs. Guidance documents from regulatory agencies in Europe and the United States have focused on patients' reported outcomes and associated quality of life. After a decade of experience with different end points that have generated some data on psychometric validation and unprecedented information about responsiveness of the binary or global end points to drug therapy, it is necessary to pursue further validation studies before or during pivotal phase IIB or III trials. The hope of providing relief to patients should galvanize all parties to achieve these goals.     

Antidepressant Therapy (Imipramine and Citalopram) for Irritable Bowel Syndrome: A Double-Blind,Randomized, Placebo-Controlled Trial

Background The efficacy of antidepressants in irritable bowel syndrome (IBS) is controversial. No trials have directly compared a tricyclic with a selective serotonin reuptake inhibitor. Our aim was to determine whether imipramine and citalopram are efficacious in IBS. Methods This was a randomized, double-blind, placebo-controlled, parallel group pilot trial with imipramine (50 mg) and citalopram (40 mg). Results Of 51 IBS patients randomized, baseline characteristics were comparable among the treatment arms; the majority was diarrhea-predominant. Adequate relief of IBS symptoms (primary endpoint) was similar for each treatment arm. Improvements in bowel symptom severity rating for interference (P = 0.05) and distress (P = 0.02) were greater with imipramine versus placebo, but improvements in abdominal pain were not. There was a greater improvement in depression score (P = 0.08) and in the SF-36 Mental Component Score (P = 0.07), with imipramine. Citalopram was not superior to placebo. Approximately 20% of the variance in scores was explained by treatment differences for abdominal pain, bowel symptom severity disability, depression and the mental component of the SF-36. Conclusion Neither imipramine nor citalopram significantly improved global IBS endpoints over placebo.     

Pharmacologic therapy for the irritable bowel syndrome

The management of the irritable bowel syndrome (IBS) remains unsatisfactory. For abdominal pain, antispasmodics are, at best, of only modest efficacy. Tricyclic antidepressants in low dose are useful (with the number needed to treat being three), but side effects and patient concerns regarding use of a centrally acting agent for depression remain limitations. Selective serotonin reuptake inhibitors are of uncertain efficacy in IBS. Opioid agonists, especially loperamide, are useful for diarrhea but not for pain in IBS; rebound constipation also remains a problem. Bile salt sequestering agents are not of established value in IBS but seem to be useful clinically in a small group of IBS patients with diarrhea. Aloestron, a 5HT(3) antagonist, should be reserved, if available, for women with severe diarrhea predominant IBS who have failed to respond to conventional therapy, and started at a low dose. Fiber and bulking agents may help constipation in some trials, but the evidence that they are efficacious in IBS is equivocal; they are frequently prescribed as first-line drugs for IBS regardless of the primary bowel disturbance but often increase bloating, gas, and pain. Laxatives are not of established value in IBS but are often taken by patients with constipation predominant IBS. Tegaserod, a partial 5HT(4) agonist, is now available in the United States and other countries for use in women with IBS whose primary bowel symptom is constipation; its efficacy in men and in those with alternating bowel habits is unknown. Probiotics are of uncertain efficacy. Chinese herbal medicine data are insufficient. Other new drugs in development include the cholecystokinin antagonists and novel visceral analgesics. Both current and potential therapies for IBS are reviewed in this article.     

抗抑郁药治疗肠易激综合征疗效荟萃分析及治疗适应证探讨

目的通过对抗抑郁药疗效的荟萃分析来探讨抗抑郁药治疗肠易激综合征(IBS)的适应证。方法检索MEDLINE、EMBASE和Cochrane对照研究登记库中IBS患者抗抑郁药治疗的随机对照研究(文献发表时间为2000-01-01-2018-03-31)。以成年IBS患者为研究人群,将抗抑郁药与安慰剂或常规治疗进行对比。以IBS的总体症状或腹痛症状无改善为结局指标,获得抗抑郁药治疗后IBS症状无改善的相对危险度(RR)和95%可信区间(CI),并根据危险差的倒数计算出所需要治疗的患者数(NNT)。对可能影响疗效的主要临床特征(即是否合并心理障碍、腹痛或腹部不适的严重程度、是否难治性IBS)和疗程进行亚组分析。结果纳入12项高质量的随机对照研究进行荟萃分析。与安慰剂或常规治疗相比,当合并抑郁或焦虑时,抗抑郁药治疗后IBS症状无改善的相对危险度是0.45(95%CI 0.26~0.80),NNT为3.7。在抑郁和焦虑未知组,难治性IBS患者抗抑郁药治疗后IBS症状无改善的相对危险度是0.58(95%CI 0.46~0.73),NNT为3.6;中-重度腹痛或腹部不适患者抗抑郁药治疗后IBS症状无改善的相对危险度是0.64(95%CI 0.44~0.93),NNT为4.7。抗抑郁药疗程≥3个月时,治疗后IBS症状无改善的相对危险度是0.66(95%CI0.54~0.81)。结论 IBS患者抗抑郁药治疗的适应证为合并抑郁或焦虑、难治性IBS、表现为中-重度腹痛或腹部不适的IBS患者;推荐疗程至少为3个月。