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舍曲林

SSRI类抗抑郁药
(重定向自舌曲林

舍曲林英語:Sertraline)(商品名:左洛复、彼迈乐等)是一种选择性5-羟色胺再吸收抑制剂(SSRI)类抗抑郁药,1991年由辉瑞制药公司发明。舍曲林主要用于治疗成人重度抑郁症(MDD),也用来治疗儿童或成人的强迫症恐慌症社交恐惧症。在2013年,舍曲林是美国零售市场处方量最大的抗抑郁药与处方量第二大的精神类药物(在阿普唑仑之后),超过4100万的舍曲林被处方给患者。[5]

舍曲林
Sertraline2DACS2.svg
Sertraline-3D-balls.png
系统(IUPAC)命名名称
(1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine
(1S-顺式)-4-(3,4-二氯苯基)-1,2,3,4-四氢-N-甲基-1-萘啶胺盐酸盐
临床数据
商品名 左洛复(Zoloft),彼迈乐, Lustral 等等[1]
Drugs.com Monograph
MedlinePlus a697048
妊娠分级
  • AU: C
  • US: C (不排除有风险的可能)
给药途径 口服
合法狀態
合法状态
药代动力学数据
生物利用度 44%
蛋白结合度 98.5%
代谢 肝脏(主要由CYP2B6酶进行N-去甲基化)[2]
生物半衰期 ~23-26小时(低活性的代谢产物去甲基舍曲林则为66小时)[3][4]
排泄 尿液
识别信息
CAS注册号79617-96-2 ✓
ATC代码 N06AB06
PubChem CID 68617
DrugBank DB01104 ✓
ChemSpider 61881 ✓
UNII QUC7NX6WMB ✓
KEGG D02360 ✓
ChEBI CHEBI:9123 ✓
ChEMBL英语ChEMBL CHEMBL809 ✓
化学信息
化学式 C17H17Cl2N
摩尔质量 306.229 g/mol

舍曲林与其他新型抗抑郁药的差别并不大,并且多只局限于副作用。与其他SSRI相比,舍曲林的耐受性与其他药物无明显差别,通常都会导致一些不良反应如腹泻恶心震颤性功能障碍体重增加。舍曲林导致腹泻的几率通常比其他SSRI要高。[6]

医疗用途编辑

舍曲林适用于多种情况包括:重度抑郁症(MDD)、强迫症(OCD)、躯体变形障碍(BDD)、创伤后应激障碍(PTSD)、经前烦躁症(PMDD)、恐慌症社交焦虑症。舍曲林也用来治疗早泄血管性头痛,但是还没有足够充分的证据证明它的效果。[7]

抑郁症编辑

一份2008年的报告指出只有51%的研究表明SSRI有积极效果。[8] 舍曲林的效果在统计学上与其他SSRI无明显差别,如帕罗西汀西酞普兰艾司西酞普兰文拉法辛(属于SNRI)等。[9][10][11][12] 证据表明在治疗某些抑郁症亚型上,舍曲林比氟西汀(百优解)效果更明显。[13]

证据指出舍曲林对儿童抑郁症的治疗没有好处。[14]

对于伴随痴呆的抑郁症,舍曲林并不优于安慰剂米氮平[15]

对比其他抗抑郁药编辑

一般认为三环类抗抑郁药(TCA)在治疗忧郁型抑郁症和住院病人上效果比SSRI更好,但并不一定对更加严重的抑郁症也有更好的效果。[16][17][18] 总的来说,舍曲林在治疗住院病人上并不优于安慰剂,在治疗重度抑郁症上与TCA类药物氯米帕明效果相当。[9] 尚未有针对在治疗忧郁型抑郁症上舍曲林与TCA的效果对比的研究。1998年有一种观点认为,由于舍曲林的药理特性,其在效果上会优于其他SSRI且在治疗忧郁型抑郁症上与TCA类药物效果相同。[19]

针对12种新型抗抑郁药的数据分析指出,舍曲林与艾司西酞普兰在治疗成人急性单极抑郁症上有着最好的效果和可接受性,而瑞波西汀的效果明显较差。[20]

具有比较性的临床试验表明,舍曲林治疗抑郁症的效果与吗氯贝胺奈法唑酮艾司西酞普兰安非他酮西酞普兰氟伏沙明帕罗西汀米氮平相似。有质量较低的证据表明,舍曲林治疗抑郁症的效果优于氟西汀[21][22][23][24][25]

针对老年患者编辑

舍曲林在治疗老年患者(大于60岁)的效果上优于安慰剂,与其它SSRI类药物氟西汀TCA类药物阿米替林去甲替林丙咪嗪效果相当。除恶心外,舍曲林的不良反应发生率低于这些TCA类药物。此外,针对大于70岁的患者,舍曲林的效果优于氟西汀去甲替林[26]2003年的一项关于舍曲林与安慰剂的对比试验得出一个具有统计学上显著(也就是说不只是偶然发生)并且具有临床意义的结论,老年患者使用舍曲林后抑郁症状有适度改善,但是生活质量并没有得到提高。[27]

强迫症编辑

舍曲林对成人及儿童的强迫症治疗均有效果。[28]基于意向性治疗分析,舍曲林相比强迫症治疗金标准氯米帕明有着更好的效果。[29]普遍认为舍曲林用于治疗强迫症的剂量比治疗抑郁症的常用剂量高。[30]舍曲林治疗强迫症的起效时间比治疗抑郁症长。治疗的建议是,以最大推荐剂量的一半最为起始剂量并持续至少两个月,在此之后如果治疗效果不明显,可将剂量提高至最大。[31]

无论是儿童还是成人,单独应用行为认知疗法的效果优于舍曲林,但是最好的方法当然是结合药物治疗。[32][33]舍曲林可能对伴随抽动秽语综合征的强迫症有疗效。[34]

恐慌症编辑

使用舍曲林治疗恐慌症可以减少惊恐发作并提高生活质量。[35] 四个双盲实验显示出舍曲林在治疗恐慌症时效果优于安慰剂,效果取决于剂量。舍曲林可以减少80%惊恐发作的几率(安慰剂为45%),并且可以减少广泛性焦虑,提升患者的生活质量。使用舍曲林的患者报告生活质量的提高程度优于安慰剂组。[35][36] 性别不会影响舍曲林的效果。[36] 如果粗略地将舍曲林与其他抗恐慌症药物(如氯米帕明丙咪嗪氯硝西泮阿普唑仑氟伏沙明帕罗西汀)进行单独比较,那么他们的效果是接近等价。[35]

其他焦虑症编辑

舍曲林可有效治疗社交恐怖症[37] Lielowitz社交焦虑量表得分的改善与舍曲林有关,但与安慰剂无关。[38]在儿童中,舍曲林和认知行为疗法(CBT)的组合对焦虑症患儿具有优异的反应率;舍曲林和CBT单独治疗也均优于安慰剂,并且彼此之间没有显著差异。[39]

有初步证据表明,舍曲林以及其他SSRI / SNRI抗抑郁药可以帮助治疗一般焦虑症的症状。[40]

经前焦虑症编辑

包括舍曲林在内的SSRI类药物可以减轻经前症状[41]常见的不良反应不良反应有恶心等。[41]

舍曲林对缓解经前焦虑症(Premenstrual dysphoric disorder,PMDD),即为重度的经前症状,效果明显。经过舍曲林治疗的人症状得到明显改善,50-60%的的人症状得到改善,而安慰剂只有20-30%。开始治疗一个星期内症状即会有明显好转,包括精神状态,易怒,焦虑等都有明显改善,这些好转还能增进家庭的和睦,社交和生活质量的提高。但是像工作能力,身体症状,如肿胀、腹胀和乳汁不足的症状并对药物并没有明显的反应。[42][43] 在黄体期,即经前12-14天服用舍曲林达到的治疗效果与在临近经前时才开始服用基本相当。[41]

其他适应症编辑

每日口服舍曲林可以治疗早发性射精(早泄、PE)。[44] SSRI类药物治疗早泄的缺点是需要长期给药才会有显著效果,并且目前还不清楚SSRI会对早泄或无法控制射精的患者造成怎样的心理困扰。[45][46]

不良反应编辑

 
美国销售的 Zoloft 50 mg & 25 mg tablets
 
澳大利亚销售的 Zoloft 100 mg tablets
 
中国销售的左洛复®盐酸舍曲林片,规格为50mg*14片

自杀倾向编辑

FDA要求包括舍曲林在内的所有抗抑郁药都要用黑框警告说明抗抑郁药会增加25岁以下服用者自杀的风险。此项警告的依据为两个独立的FDA专家组的统计分析,结果显示儿童和青少年产生自杀意向和行为的几率提高两倍,18-24岁的人群则提高1.5倍。[47][48][49]

过量服用编辑

急性过量服用舍曲林的症状通常为呕吐、嗜睡,运动失调,心动过速和癫痫发作。血浆、血清或血液中舍曲林和去甲基舍曲林(舍曲林的活性代谢产物)是诊断是否过量服用的标志,也可以帮助法医进行死因调查。[50] 与其他大部分SSRI一样,舍曲林服用过量的毒性是相对较小的。[51][52]

作用机制编辑

舍曲林主要是一种5-羟色胺再摄取抑制剂,对5-羟色胺转运体的亲和力是Ki=2.0μM.[53] 在服用4周治疗剂量的舍曲林 (25–200 mg/天) 后,通过正电子发射断层扫描测量纹状体得知,舍曲林抑制80–90%的5-羟色胺转运体。每日9mg剂量时则抑制50%的5-羟色胺转运体。[54]

药代动力学编辑

 
去甲基舍曲林, 舍曲林的主要活性代谢产物

舍曲林口服吸收缓慢,在4-6小时时达到最大血药浓度。舍曲林在血液中的蛋白结合度为98.5%。舍曲林在体内的生物半衰期为13-45小时,并且平均女性(32小时)比男性(22小时)长1.5倍。 [55]体外研究显示,舍曲林由多种细胞色素P450同工酶代谢,包括:CYP2D6, CYP2C9, CYP2B6, CYP2C19CYP3A4。但是对上述任意一种同工酶的抑制都不能使舍曲林的药代动力学数据发生具有临床意义的改变。[2][56] CYP2D6活性不同的人对舍曲林的代谢无影响,[57] 然而,低活性的CYP2C19会使舍曲林的代谢时间延长1.5倍。[58][2] [2][59]

舍曲林的非胺类代谢产物也具有抗抑郁作用。脱氨基舍曲林代号为O-2098,尽管它并没有氮原子,但是体外研究仍表明其具有抑制多巴胺再摄取的作用。[60]

舍曲林的首要代谢产物,諾舍特拉林(norsertraline/N-去甲舍曲林),是一种生物活性比舍曲林低很多的物质。[61]

參見编辑

引用编辑

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