选择性5-羟色胺再摄取抑制剂类药物的研究进展

选择性5-羟色胺再摄取抑制剂(SSRIs)类药物始用于20世纪80年代,因其具有对5-羟色胺(5-HT)选择性高,对其他递质影响小,尤其对心血管系统和胆碱能作用较少,而半衰期普遍较长,患者依从性较好等优点,逐渐受到医患青睐,成为目前治疗抑郁症的一线药物,在临床上使用最为广泛,已占据世界抗抑郁药市场一半以上的份额。截至2008年底有8种畅销抗抑郁药销售额合计超过全球抗抑郁药市场的80%,而SSRIs类药物包揽了前4名。然而,我国的抗抑郁药市场长期以来发展速度较为缓慢。为尽快提升我国抑郁症人群治疗水平,充分开发抗抑郁药物市场,对SSRIs类药物的研究进展进行综述,以期为临床医师提供更详尽的、前沿的一手资料,从而更好地满足广大患者的临床需要。     

选择性5-羟色胺再摄取抑制剂应用与评价

目的:抑郁症是神经内科的常见和多发病,伴随着对抑郁发病机制的解译,治疗新药不断问世,本文介绍选择性5-羟色胺再摄取抑制剂进展和临床应用的侧面。方法:采用国内、外文献综述方法。结果及结论:作为抗抑郁药中的一支奇葩,选择性5-羟色胺再摄取抑制剂进展迅猛,对5-HT受体有高度的选择性,标志一个新的里程的开始,从而在解除抑郁症上展现了良好的治疗前景。     

选择性5-羟色胺再摄取抑制剂应用与评价研究

目的：选择性5-羟色胺再摄取抑制剂的应用和评价研究。方法：随机选取我院在2013年4月～2014年4月抑郁症患者72例作为研究对象,将其随机分为观察组和对照组,每组36例。为对照组患者采用常规的治疗方法予以治疗,观察组患者在常规治疗基础上配合选择性5-羟色胺再摄取抑制剂进行治疗,观察并比较两组患者的治疗效果,予以评价研究。结果：观察组患者的治疗效果明显优于对照组,有效治疗患者32例,治疗有效率为88.89%,对照组有效治疗患者21例,治疗有效率为58.33%,P＜0.05,具有统计学意义。此外,观察组患者的满意率明显高于对照组,P＜0.05,具有统计学意义。结论：选择性5-羟色胺再摄取抑制剂治疗抑郁症具有显著效果,可以提高患者的治愈率,更容易得到患者的接受和认可,值得在临床上推广使用。     

选择性5-羟色胺再摄取抑制剂引起低钠血症26例报告

选择性5-羟色胺再摄取抑制剂(SSRI)以其疗效与三环类抗抑郁药(TCA)相近,而不良反应明显减少,近十年来,在临床上得到广泛应用;尤其是在门诊治疗中,由于其副反应少,在老年病人中,使用率越来越大,作者在临床工作中,发现26例抑郁症病人使用SSRI类药后引起低钠血症,现报道如下:     

基于药物基因组学的选择性5-羟色胺再摄取抑制剂个体化治疗抑郁症

选择性5-羟色胺再摄取抑制剂(SSRIs)是当前治疗抑郁症的一线药物,CYP2D6、CYP2C19基因多态性会影响SSRIs的代谢,进而影响其疗效与安全性.目前我国临床医师对抑郁症患者基于基因多态性的SSRIs个体化治疗实践相对较少.该文就CYP2D6、CYP2C19基因型及其对SSRIs治疗的影响进行综述,以期为抑郁...     

选择性5-羟色胺再摄取抑制剂与奥氮平联合治疗难治性抑郁症的临床疗效

目的 探讨选择性5-羟色胺再摄取抑制剂与奥氮平联合治疗难治性抑郁症的临床疗效.方法 选择2009年1月-2012年1月门诊和住院治疗的难治性抑郁症84例,随机分为对照组和治疗组各42例.对照组单纯应用选择性5-羟色胺再摄取抑制剂;治疗组在对照组药物的基础上加用奥氮平,比较两组药物治疗难治性抑郁症的临床疗效;结果 两组患者汉密尔顿抑郁量表评分治疗后均比治疗前有明显降低,差异具有统计学意义(P＜0.01);治疗组痊愈21例(50.0％),显著10例(23.8％),总有效率为73.8％;对照组痊愈10例(23.8％),显著11例(26.2％),总有效率为50.0％,治疗组总有效率优于对照组,差异具有统计学意义(P＜0.05).两组患者均出现一些轻微的不良反应,但差异不具有统计学意义(P＞0.05)).结论 选择性5-羟色胺再摄取抑制剂联合奥氮平治疗难治性抑郁症临床疗效较好,且不良反应较少,两者可联合应用于临床.     

选择性5-羟色胺再摄取抑制剂致不良反应文献分析

目的探讨选择性5-羟色胺再摄取抑制剂(SSRI)致药品不良反应(ADR)的规律和特点,为临床合理用药提供参考.方法 检索2004年1月-2014年12月中国期刊全文数据库(CNKI)、万方数字化期刊全文库、中文科技期刊全文数据库(维普)、中国医院知识总库(CHKD)等数据库报道的SSRI致ADR的文献,并进行分析和讨论.结果 SSRI引发的ADR女性明显多于男性,年龄多集中于41~60岁;抑郁症发生的ADR例数最多;在引发ADR的SSRI中,帕罗西汀的发生率最高;服药4周后出现ADR的例数最多,占30.5%;有25例联合用药,其中帕罗西汀联合用药的例数最多;SSRI引发的ADR以神经系统损害为主,占44.9%.结论 SSRI引发的ADR较为常见,临床使用时应及时处理,以确保患者用药安全.     

选择性5-羟色胺再摄取抑制剂致不良反应文献分析

目的:警示选择性5-羟色胺再摄取抑制剂(SSRI)的不良反应。方法:汇总2001~2006年国外文献报道的SSRI致不良反应病例,并对其临床表现及安全性进行分析。结果:该类药物不良反应主要涉及生殖系统、心脑血管系统、中枢神经系统及消化系统等。结论:临床应重视该类药物的不良反应,警惕应用本品诱发严重的不良反应,特别是老人、儿童及孕妇。     

选择性5-羟色胺再摄取抑制剂致锥体外系反应2例

1 病例 例1,男,17岁,诊断:癔症.既往史、家族史阴性.予帕罗西汀20 mg/d治疗,2天后出现痉挛性斜颈,体格检查:心肺阴性,腹软,肝脾未触及.四肢肌张力正常.给予氢溴酸东莨菪碱0.3 mg,肌内注射,症状缓解,后又出现3次痉挛性斜颈,均在肌注氢溴酸东莨菪碱0.3 mg后缓解,后加用苯海索2 mg,每日2次治疗,未再出现痉挛性斜颈.     

选择性5-羟色胺再摄取抑制剂安全性研究概述

选择性5-羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors，SSRIs）是广泛应用的新型抗抑郁药，用于治疗各种抑郁症。常用的SSRIs有氟西汀、帕罗西汀、舍曲林、氟伏沙明及西酞普兰。SSRIs有多种类型的不良反应，主要为胃肠道反应、停药反应、性功能障碍及抗利尿激素异常分泌综合征等。SSRIs有可能增加儿童和青少年自杀意念和行为的风险，但目前尚无定论。最新研究表明，孕妇早期服用SSRIs似乎不增加胎儿先天畸形风险，但孕妇晚期服用SSRIs，可致新生儿出现肺动脉高压和停药综合征。一般而言，用含SSRIs的母乳喂养是安全的，因其在乳汁中的含量很低，但长期服用对婴儿发育的影响尚不清楚。对于老年人，SSRIs可增加骨折风险。SSRIs和某些药物联用发生相互作用导致的不良反应如下：单胺氧化酶抑制剂：5-羟色胺综合征；利尿剂：严重低钠血症；抗凝血药：增加出血危险；非甾体抗炎药：增加上消化道出血风险；色氨酸：5-羟色胺综征；阿司咪唑、特非那定：室性心律失常，Q-T间期延长；氟哌啶醇、马普替林：严重锥体外系反应；锂盐：锂血浓度升高，毒性增加。总之，SSRIs的不良反应虽然少于三环类抗抑郁药，但其有自身特有的不良反应。因此，医师临床使用SSRIs应予以注意。     

Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube

Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage‐dependent channels for Na⁺, K⁺ and Ca²⁺, but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10^?9 M/L to 1.4 × 10^?6 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10^?8 M/L, r = 0.580, P < 0.05) (F = 2.980, df₁ = 6, df₂ = 28, P < 0.05). Paroxetine (from 1.2 × 10^?9 M/L to 5.1 × 10^?5 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10^?8 M/L, r = 0.500, P < 0.05) (F = 2.350, df₁ = 9, df₂ = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.     

Treatment of selective mutism: focus on selective serotonin reuptake inhibitors

Abstract Selective mutism is a pediatric psychiatric disorder that occurs when a child consistently fails to speak in specific situations in which speaking is expected, such as at school and social gatherings, but speaks appropriately in other settings. Selective mutism often is diagnosed when a child starts school and does not talk to teachers or peers, but talks to family members at home; the condition is frequently accompanied by anxiety and shyness. Although the underlying etiology of the condition remains unclear, psychotherapy is the preferred initial treatment, with the support of parents and teachers. If the child does not respond to psychotherapy, addition of pharmacologic treatment should be considered, depending on the severity of symptoms and presence of other illnesses. Although data are limited to case reports and trials with small patient populations and short follow-up periods, some patients with selective mutism respond to therapy with selective serotonin reuptake inhibitors (SSRIs). Fluoxetine is the most studied SSRI as treatment for the condition, although further investigation is required to determine the optimal dosage and duration of therapy.     

Safety of selective serotonin reuptake inhibitors in pregnancy

Psychiatric treatment with selective serotonin reuptake inhibitors (SSRIs) may be desirable or necessary during pregnancy; however, the benefit of these treatments must balance the benefits to the mother with any risk to the developing foetus. At the present time, the role of serotonin in normal central nervous system development, as well as the effects of altering serotonin transmission at critical periods of embryo development, remains to be further clarified. Depression has a high prevalence in pregnant women (around 10%) and approximately one-half of the pregnancies are unplanned, making necessary that physicians have to know the risks associated with the decision to use this kind of antidepressants during pregnancy. The effects of antidepressants in pregnancy could be classified in several main categories: the teratogenic possible effects; the effects on the normal development of the brain and neuropsychological functions; the effects on birth weight and/or early delivery; the risk of increased bleeding on the mother during delivery; the neuropsychological behaviour and adaptation after delivery, including not only neonatal withdrawal syndromes but also pain reactivity and increased parasympathetic cardiac modulation during recovery after an acute noxious event and in a wide range of neurobehavioural outcomes; and medium- to long-term effects in neurocognitive functions in those children. These areas are reviewed according to the most recent published cohort-controlled studies and prospective surveys regarding SSRIs use in pregnancy. The review tries to clarify the blurred aspects of the use of SSRI during pregnancy and to give sensible and up-to-dated guidelines for the treatment of psychiatric disorders with SSRI during pregnancy.     

The analgesic effects of selective serotonin reuptake inhibitors

This paper endeavours to provide a critical clinical review of the use of selective serotonin reuptake inhibitors (SSRIs) in the management of pain. Case reports, placebo-controlled trials and trials comparing SSRIs with tricyclic antidepressants (TCAs) are considered. The analgesic effects of TCAs are well known and this review suggests that there is little evidence for their replacement by SSRIs in pain management. There are, at present, too few comparative drug trials to make a definitive statement, although the trend is clearly against SSRIs.     

Utility of selective serotonin reuptake inhibitors in premature ejaculation

The introduction of selective serotonin reuptake inhibitors (SSRIs) has revolutionized our understanding of the treatment of premature ejaculation. Lifelong premature ejaculation may be a neurobiological phenomenon, namely part of a biological variability of the intravaginal ejaculation latency time in men. Animal studies support this view, and an animal model for premature and delayed ejaculation has recently been developed. It is proposed that drug treatment of premature ejaculation should consist of 5-hydroxytryptamine (5-HT)2c receptor stimulation and/or 5-HT1A receptor inhibition. A meta-analysis of 35 daily treatment studies with selective serotonin reuptake inhibitors (SSRIs) and clomipramine demonstrated comparable efficacy of clomipramine with the SSRIs sertraline and fluoxetine in delaying ejaculation, whereas the efficacy of the SSRI paroxetine was greater than all other SSRIs and clomipramine. It is postulated that acute treatment with SSRIs, including those with short half-lives, will not produce an ejaculation delay equivalent to that induced by daily treatment of SSRIs.     

Effects of selective serotonin and serotonin/noradrenaline reuptake inhibitors on extracellular serotonin in rat diencephalon and frontal cortex

Some clinical reports suggest that tricyclic antidepressants which block both noradrenaline and serotonin (5-HT) reuptake (SNRIs) are more effective than selective 5-HT reuptake inhibitors (SSRIs) in treating severe depression. Moreover, one neurochemical study reported larger increases in extracellular 5-HT in rat frontal cortex in response to the tricyclic antidepressant imipramine compared to the SSRI fluoxetine. However, imipramine, which blocks both 5-HT and noradrenaline reuptake, also binds with relatively high affinity to receptors for noradrenaline, histamine and acetylcholine. Thus, to test the hypothesis that compounds that inhibit both 5-HT and noradrenaline reuptake produce larger increases in 5-HT efflux, we compared the effects of acute systemic administration of several SNRIs and SSRIs. Extracellular 5-HT was measured using microdialysis probes implanted in the diencephalon and frontal cortex of unanesthetized rats. We tested the SSRIs paroxetine (0.3-10 mg/kg), citalopram (10-20 mg/kg) and fluoxetine (10 mg/kg), the nonselective tricyclic antidepressant imipramine (20 mg/kg) and the more selective SNRIs duloxetine (3-30 mg/kg) and venlafaxine (30-50 mg/kg). During the lights-off period, paroxetine and duloxetine increased 5-HT in the diencephalon approximately 300 and approximately 200%, respectively. During the lights-on period, paroxetine and duloxetine each increased 5-HT approximately 400% in the diencephalon. In the frontal cortex, both paroxetine and duloxetine increased 5-HT approximately 200%. Citalopram and venlafaxine each increased 5-HT in the diencephalon approximately 300%. Fluoxetine and imipramine increased 5-HT in the diencephalon by approximately 125 and approximately 80%, respectively. Thus, these results do not support the hypothesis that compared to SSRIs, compounds which inhibit both 5-HT and noradrenaline reuptake have a larger acute effect on extracellular 5-HT.