米氮平

维基百科,自由的百科全书
跳到导航 跳到搜索
米氮平
Mirtazapine 2D structure.svg
Mirtazapine-3D-ball-model.png
系统(IUPAC)命名名称
(±)-2-methyl-1,2,3,4,10,14b-hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine
临床数据
商品名 瑞美隆(中国大陆)/樂活憂(港台)(Remeron)
Drugs.com Monograph
MedlinePlus a697009
医疗法规
妊娠分级
  • AU: B3
  • 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 50%[1][2][3][4]
蛋白结合度 85%[1][2][3][4]
代谢 肝脏 (CYP1A2, CYP2D6CYP3A4)[1][2][3][4][5]
生物半衰期 20–40小时[1][2][3][4]
排泄 尿液 (75%)[1]
粪便 (15%)[1][2][3][4]
识别信息
CAS注册号61337-67-5 ✓
ATC代码 N06AX11
PubChem CID 4205
IUPHAR/BPS英语IUPHAR/BPS 7241
DrugBank DB00370 ✓
ChemSpider 4060 ✓
UNII A051Q2099Q ✗
KEGG D00563 ✓
ChEBI CHEBI:6950 ✗
ChEMBL英语ChEMBL CHEMBL654 ✓
其他名称 6-Azamianserin, Org 3770
化学信息
化学式 C17H19N3
摩尔质量 265.35 g/mol
物理性质
密度 1.22 g/cm3
熔点 114至116 °C(237至241 °F)
沸点 432 °C(810 °F)
水溶液 溶于甲醇氯仿 mg/mL (20 °C)
 ✗✓ (what is this?)英语Wikipedia:WikiProject_Chemicals/Chembox_validation  (verify)

米氮平(英语:Mirtazapine,商品名为樂活憂(港台)/瑞美隆(中国大陆)(Remeron)[6],是一种去甲肾上腺素和特异性5-羟色胺能抗抑郁药 (NaSSA) [2] ,主要用来治疗抑郁症。米氮平也经常被用作抗焦虑药安眠药止吐药食欲促进剂。若按分子结构分类,米氮平被分类为四环类抗抑郁药(TeCA) ,并且为米安舍林的6-氮杂类似物。[6] 米氮平也是一种外消旋混合物,包含(R)- 和 (S)-异构体[6]

医疗用途[编辑]

已批准的和适应症外使用[编辑]

米氮平主要用来治疗重度抑郁症和其他精神障碍。[7][8]

然而研究发现,米氮平对以下症状也有一定疗效,所以米氮平有时候也会被以适应症外使用的形式处方给以下症状的治疗:

研究性的[编辑]

有过文献报道的使用米氮平进行过实验性治疗的症状包括:

有效性和耐受性[编辑]

2010年,NICE发布了治疗抑郁症的指南,其中包括对抗抑郁药的综述。它建议将通用SSRIs作为第一线选择,因为它们“与其他抗抑郁药同样有效并且具有有利的风险-效益比”。[40]关于米氮平,它发现:“米氮平与其他抗抑郁药在任何疗效指标上没有差异,尽管在达到缓解方面,米氮平似乎具有统计学但不具有临床意义的优势。此外,米氮平具有优于SSRIs的统计学优势。就减少抑郁症状而言,这种差异在临床上并不重要。然而,有强有力的证据表明服用米氮平的患者由于副作用而不太可能提早离开治疗,尽管对于报告副作用的患者不是这种情况或因任何原因提早离开治疗。“[41]]

2011年Cochrane评价将米氮平与其他抗抑郁药进行了比较,结果发现,虽然它对患者的起效较快(在第2周时),但在第6周时它与其他的抗抑郁药大致相同。[42]

一项针对抗抑郁药和睡眠的2012年评论发现,在许多因抑郁引起睡眠障碍的患者中,米氮平减少了入睡所需的时间并提高了睡眠质量,但在某些人中,它会扰乱睡眠,有8%至28%的人会有不安腿综合征,并且它在极少数情况下导致REM睡眠行为障碍。

2018年有项系统评价和网络荟萃分析比较了12种抗抑郁药物的疗效和耐受性,结果显示米氮平是头对头研究中最有效的抗抑郁药之一。[43]

在第1周之后,相较于SSRI,米氮平有着更快的起效时间。[44][45]

副作用[编辑]

2011年Cochrane评价发现,与其他抗抑郁药相比,它更容易引起体重增加和嗜睡,但它比三环类抗抑郁药引起震颤的可能性更小,并且比SSRIs更不可能引起恶心和性功能障碍。[46]

米氮平不被认为存在很多副作用的风险,这些副作用通常和其他抗抑郁药,例如SSRI,有关,并且当他们一起使用时可以改善某些副作用。这些不良反应包括食欲减退,体重减轻,失眠恶心呕吐腹泻尿潴留体温升高,出汗过多,瞳孔扩张和性功能障碍[47][48]

一般地,有些抗抑郁药,例如SSRI,会自相矛盾地加剧一些人的抑郁或焦虑或自杀意念。[49]尽管米氮平具有镇静作用,但据信也有能力做到这一点,所以在美国和其他一些国家,它带有黑框标签来警告这些潜在的影响。

2000年发表的一份病例报告指出,米氮平可以抵消可乐定的作用,导致血压升高。[50]

不良反应发生率[51][编辑]

非常常见(≥1/10)

  • 体重增加
  • 食欲增加
  • 嗜睡
  • 镇静作用
  • 口干

常见(≥1/100~<1/10)

  • 梦异常
  • 意思混乱
  • 焦虑
  • 失眠

不常见(≥1,000~<1/100)

罕见(≥1/10,000~>1/1,000)

  • 肌痉挛
  • 血清氨基转移酶增加

频率不详

停药[编辑]

米氮平和其他抗抑郁药可能在停止服用后引发停药综合征。[47][52][53]建议逐渐缓慢减少剂量,以尽量减少停药综合征。[54]突然停止米氮平治疗的后果可能包括抑郁,焦虑耳鸣惊恐发作眩晕,精神运动激动,易怒食欲减退失眠腹泻恶心呕吐流感类似过敏瘙痒症头痛,有时会有轻度躁狂躁狂症[52][55][56][57][58]

药物相互作用[编辑]

与细胞色素(CYPP450同工酶CYP1A2CYP2D6和/或CYP3A4的抑制剂或诱导剂同时使用可导致米氮平的浓度改变,因为这些是负责其代谢的主要酶。[59][60]例如,已知氟西汀帕罗西汀(这些酶的抑制剂)适度增加米氮平水平,而卡马西平(一种诱导剂)可显著降低米氮平水平。[59]据报道,在肝功能损害和中度肾功能损害的人群中,米氮平口服清除率降低约30%;而严重肾功能损害患者的口服清除率减少50%。[59]

根据制造商提供的信息,米氮平不应在任何单胺氧化酶抑制剂MAOI)停用后两周内开始使用;同样,MAOI不应在停用米氮平后两周内给药。[61]米氮平与SSRISNRITCA联合作为增强策略被认为是相对安全的,而且通常用于治疗。[62]文拉法辛和米氮平的组合,有时被称为“加州火箭燃料”。[63][64]已知在氟西汀和米氮平同时给药的情况下可能发生5-羟色胺综合征

过量[编辑]

如果服用过量,米氮平被认为是相对安全的[65],尽管过量服用的毒性比大多数SSRIs(西酞普兰除外)略高。[66]与三环类抗抑郁药不同,米氮平在最大推荐剂量的7至22倍时未显示出明显的心血管不良反应。[67]与三环类抗抑郁药相比,过量服用标准剂量30至50倍的病例报告称药物相对无毒。[68][69]

据报道,有12人死于米氮平过量。[70][71]米氮平的致命毒性指数(每百万处方死亡人数)为3.1(95%CI:0.1至17.2)。这类似于用SSRIs观察到的情况。[72]

药理学[编辑]

药效学[编辑]

米氮平[73]
Ki(nm) 物种 来源 参考
SERT >10,000 人类 [74][75]
NET ≥4,600 人类 [76][74]
DAT >10,000 人类 [77][78]
5-HT1A 3,330~5,010 人类 [47][78]
5-HT1B 3,534~12,600 人类 [47][75]
5-HT1D 794-5,010 人类 [47][75]
5-HT1E 728 人类 [75]
5-HT1F 583 人类 [75]
5-HT2A 6.3~69 人类 [47][75][79]
5-HT2B 200 人类 [47]
5-HT2C 8.9~39 人类 [47][75][79]
5-HT3 7.9 人类 [47]
5-HT4L >10,000 人类 [75]
5-HT5A 670 人类 [75]
5-HT6 ND ND ND
5-HT7 265 人类 [75][79]
α1A 316~1,815 人类 [75]
α2A 20 人类 [75][79]
α2B 88 人类 [75]
α2C 18 人类 [75][79]
β >10,000 人类 [75]
D1 ~4167 大鼠 [79]
D2 >5,454 人类 [75][79]
D3 5723 人类 [75][79]
D4 2,518 人类 [75]
H1 0.14~1.6 人类 [47][75][79][80]
H2 >10,000 大鼠 [80][81]
H3 83,200 人类 [81]
H4 >100,000 人类 [81]
mAch 670 人类 [47][76]
VGSC 6,905 大鼠 [75]
VDCC >10,000 大鼠 [75]

米氮平有时被分类为去甲肾上腺素和特异性五羟色胺能能抗抑郁药(NaSSA),[47]尽管支持此分类的证据并不可靠。[82]米氮平有抗去甲肾上腺素、组胺和5-羟色胺受体的功效。它特别是α 2A ,α2B,和α2C肾上腺素能受体、组胺H1受体和5-羟色胺5-HT2A、5-HT2C和5-HT3拮抗剂反向激动剂。不同于许多其他的抗抑郁药,它不抑制5-羟色胺、去甲肾上腺素或多巴胺的再摄取,也不抑制单胺氧化酶。同多数抗抑郁药类似,米氮平的抗胆碱能、阻断钠离子通道或阻断钙离子通道的效应很弱甚至没有。然而在过量食用时,米氮平具有更好的耐受性和低毒性。米氮平是TCA或TeCA中最有效的H1受体拮抗剂,拮抗H1受体是米氮平最强的活性,它在低剂量下为选择性H1受体拮抗剂。

米氮平的(S)-(+)对映体负责5-羟色胺5-HT2A和5-HT2C的拮抗作用,(R)-(-)对映体负责对5-HT3受体的拮抗作用。虽然(R)-(-)是很强的组胺H1受体的拮抗剂,两种对映体都参与了对组胺H1受体和肾上腺素α2受体的拮抗作用。

虽然没有临床意义,已经发现米氮平在高浓度的情况下是κ阿片样受体部分激动剂(EC50=7.2nm)。

α2肾上腺素受体[编辑]

作为α2肾上腺素能受体的拮抗剂,其功能主要是由于抑制自受体和异受体,提高去甲肾上腺素和5-羟色胺能的神经传递,特别是中央 5-HT1A受体介导的中缝背核和海马神经递质的传导;因此,米氮平的分类为NaSSA。间接地增强α1肾上腺素受体介导的5-羟色胺细胞放电和抑制、直接阻断5-羟色胺神经元上的异受体会增加细胞外5-羟色胺的浓度。因此,米氮平被认为是5-HT1A受体的“间接激动剂 ”。中枢5-HT1A受体的活动增加被认为是大多数抗抑郁药物功效的主要原理。

5-HT2和5-HT3受体[编辑]

对5-HT2受体亚族的拮抗作用和对5-HT2C受体的反向激动作用似乎是米氮平治疗抑郁的机理之一。米氮平能增加前额叶皮质中的多巴胺能,对大鼠的研究结果表明,阻断α2肾上腺素能受体和5-HT2C受体能对大鼠的此区域对多巴胺的释放去抑制。米氮平对5-HT2A受体的拮抗作用对焦虑、失眠和性功能有改进。已证明米氮平可以降低人类和各种动物的寻药行为。它也正在被研究对物质滥用的行为,以减少戒断效应和提高缓解率。

由于对5-HT3受体的拮抗作用,米氮平与批准的止吐药昂丹司琼有着共同的作用,它可显著改善病人的恶心、呕吐、腹泻肠易激综合征的症状。米氮平可作为一种廉价的止吐药以替代昂丹司琼。在一些研究中,在一些研究中,也发现米氮平对5-HT3受体的阻断可以改善焦虑并有效治疗物质依赖。与物质滥用咨询相结合,米氮平成功地减少了对冰毒依赖的个体对冰毒的使用。与米氮平相比,SSRIs,SNRIs,MAOIs和一些TCAs增加了5-HT2A,5-HT2C和5-HT3受体的一般活性,造成负面结果和副作用,其中最突出的包括厌食、失眠和性功能障碍(丧失主动的性欲、性快感缺失)以及恶心和腹泻等等。因此,它通常与这些药物结合使用,以减少其副作用,并产生更强的抗抑郁作用。

米氮平不具有5-羟色胺能活性,不会引起5-羟色胺能副作用或5-羟色胺综合征。这与其不是5-羟色胺再摄取抑制剂或MAOI,也不是血清素受体激动剂的事实一致。没有关于单独使用米氮平的5-羟色胺综合征的报道,并且未发现米氮平过量引起5-羟色胺综合征。但是,有一些案例报告米氮平与SSRIs等5-羟色胺能药物联合应用引起5-羟色胺综合征,尽管这些报道非常罕见,并不一定暗示米氮平是致病因素。在MAOI中加入米氮平不会引起5-羟色胺综合征,并被认为是一种安全的组合。此外,米氮平实际上可用于治疗5-羟色胺综合征,至少有一家出版物发现它可有效地解决该综合征。这是按照5-HT2A受体是主要的5-羟色胺受体,被认为参与5-羟色胺综合征的病理生理学(而5-HT1A受体似乎是保护性的)。米氮平是一种有效的5-HT2A受体拮抗剂,而赛庚啶是一种具有这种特性的药物,可介导5-羟色胺综合征的恢复,并且在临床上已成熟,可作为对抗它的解毒剂。

H1接受体[编辑]

米氮平是一种非常强的H1受体反向激动剂,因此,它可以引起强大的镇静和催眠作用。米氮平于健康志愿者的单15毫克剂量已被发现导致在H1受体的80%以上的占用并诱导强烈的嗜睡。但是,经过长时间的慢性治疗,H1会脱敏,并且抗组胺能的效应变得更耐受。许多患者也可能在晚上服用以避免这种影响,这似乎是对抗它们的有效策略。阻断H1受体可以改善先前存在的患病个体的过敏瘙痒、恶心和失眠。然而,它也可能有助于增加体重。与H1受体相反,米氮平仅对毒蕈碱乙酰胆碱受体仅具有低亲和力,尽管在临床实践中有时仍会出现口干、便秘瞳孔散大抗胆碱能副作用。

药代动力学[编辑]

米氮平的口服生物利用度约为50%。有85%结合到血浆蛋白。它主要在肝脏中通过去甲基化细胞色素P450酶羟基化代谢,其主要代谢物之一是去甲基米氮平。整体清除半衰期为20~40小时。约15%由粪便、75%由尿液排出。

引用[编辑]

  1. ^ 1.0 1.1 1.2 1.3 1.4 1.5 Timmer, CJ; Sitsen, JM; Delbressine, LP. Clinical pharmacokinetics of mirtazapine. Clinical Pharmacokinetics. June 2000, 38 (6): 461–74. PMID 10885584. doi:10.2165/00003088-200038060-00001. [永久失效連結]
  2. ^ 2.0 2.1 2.2 2.3 2.4 2.5 REMERON (mirtazapine) tablet, film coated [Organon Pharmaceuticals USA]. DailyMed. Organon Pharmaceuticals USA. October 2012 [24 October 2013]. 
  3. ^ 3.0 3.1 3.2 3.3 3.4 Axit Mirtazapine PRODUCT INFORMATION. TGA eBusiness Services. alphapharm. 25 October 2011 [15 October 2013]. 
  4. ^ 4.0 4.1 4.2 4.3 4.4 Mirtazapine 30 mg Tablets - Summary of Product Characteristics. electronic Medicines Compendium. Sandoz Limited. 20 March 2013 [24 October 2013]. (原始内容 (PDF)存档于2013-10-29). 
  5. ^ 5.0 5.1 Anttila, SA; Leinonen, EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Reviews. 2001, 7 (3): 249–64. PMID 11607047. doi:10.1111/j.1527-3458.2001.tb00198.x. 
  6. ^ 6.0 6.1 6.2 Brayfield, A (编). Mirtazapine. Martindale: The Complete Drug Reference (The Royal Pharmaceutical Society of Great Britain). 30 January 2013 [3 November 2013]. 
  7. ^ Gorman, JM. Mirtazapine: clinical overview. J Clin Psychiatry. 1999,. 60 Suppl 17: 9–13; discussion 46–8. PMID 10446735. 
  8. ^ Benjamin, S; Doraiswamy, PM. Review of the use of mirtazapine in the treatment of depression. Expert Opinion on Pharmacotherapy. July 2011, 12 (10): 1623–32. PMID 21644844. doi:10.1517/14656566.2011.585459. 
  9. ^ Goodnick, PJ; Puig, A; DeVane, CL; Freund, BV. Mirtazapine in major depression with comorbid generalized anxiety disorder. J Clin Psychiatry. July 1999, 60 (7): 446–8. PMID 10453798. doi:10.4088/JCP.v60n0705. 
  10. ^ 10.0 10.1 10.2 10.3 Croom, KF; Perry, CM; Plosker, GL. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009, 23 (5): 427–52. PMID 19453203. doi:10.2165/00023210-200923050-00006. [永久失效連結]
  11. ^ Muehlbacher, M; Nickel, MK; Nickel, C; 等. Mirtazapine treatment of social phobia in women: a randomized, double-blind, placebo-controlled study. Journal of Clinical Psychopharmacology. December 2005, 25 (6): 580–3. PMID 16282842. doi:10.1097/01.jcp.0000186871.04984.8d. 
  12. ^ Koran, LM; Quirk, T; Lorberbaum, JP; Elliott, M. Mirtazapine treatment of obsessive-compulsive disorder. J Clin Psychopharmacol. October 2001, 21 (5): 537–9. PMID 11593084. doi:10.1097/00004714-200110000-00016. [不可靠的醫學來源?]
  13. ^ Carpenter, LL; Leon, Z; Yasmin, S; Price, LH. Clinical experience with mirtazapine in the treatment of panic disorder. Ann Clin Psychiatry. June 1999, 11 (2): 81–6. PMID 10440525. doi:10.3109/10401239909147053. [不可靠的醫學來源?]
  14. ^ Carli, V; Sarchiapone, M; Camardese, G; Romano, L; DeRisio, S. Mirtazapine in the treatment of panic disorder. Arch. Gen. Psychiatry. July 2002, 59 (7): 661–2. PMID 12090820. doi:10.1001/archpsyc.59.7.661. [不可靠的醫學來源?]
  15. ^ Landowski, J. [Mirtazapine--an antidepressant]. Psychiatria Polska. 2002, 36 (6 Suppl): 125–30. PMID 12647431 (波兰语). 
  16. ^ Chinuck, RS; Fortnum, H; Baldwin, DR. Appetite stimulants in cystic fibrosis: a systematic review. Journal of Human Nutrition and Dietetics : the Official Journal of the British Dietetic Association. December 2007, 20 (6): 526–37. PMID 18001374. doi:10.1111/j.1365-277X.2007.00824.x. 
  17. ^ Davis, MP; Khawam, E; Pozuelo, L; Lagman, R. Management of symptoms associated with advanced cancer: olanzapine and mirtazapine. A World Health Organization project. Expert Review of Anticancer Therapy. August 2002, 2 (4): 365–76. PMID 12647979. doi:10.1586/14737140.2.4.365. 
  18. ^ Hartmann, PM. Mirtazapine: a newer antidepressant. Am Fam Physician. January 1999, 59 (1): 159–61. PMID 9917581. 
  19. ^ Jindal, RD. Insomnia in patients with depression: some pathophysiological and treatment considerations. CNS Drugs. 2009, 23 (4): 309–29. PMID 19374460. doi:10.2165/00023210-200923040-00004. [永久失效連結]
  20. ^ Nutt, DJ. Tolerability and safety aspects of mirtazapine. Human Psychopharmacology. June 2002,. 17 Suppl 1: S37–41. PMID 12404669. doi:10.1002/hup.388. 
  21. ^ 21.0 21.1 Li, TC; Shiah, IS; Sun, CJ; Tzang, RF; Huang, KC; Lee, WK. Mirtazapine relieves post-electroconvulsive therapy headaches and nausea: a case series and review of the literature. The Journal of ECT. June 2011, 27 (2): 165–7. PMID 21602639. doi:10.1097/YCT.0b013e3181e63346. 
  22. ^ Kast, RE; Foley, KF. Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects. Eur J Cancer Care (Engl). July 2007, 16 (4): 351–4. PMID 17587360. doi:10.1111/j.1365-2354.2006.00760.x. 
  23. ^ Twycross, R; Greaves, MW; Handwerker, H; 等. Itch: scratching more than the surface. QJM : Monthly Journal of the Association of Physicians. January 2003, 96 (1): 7–26. PMID 12509645. doi:10.1093/qjmed/hcg002. 
  24. ^ Greaves, MW. Itch in systemic disease: therapeutic options. Dermatologic Therapy. 2005, 18 (4): 323–7. PMID 16297004. doi:10.1111/j.1529-8019.2005.00036.x. 
  25. ^ Colombo, B; Annovazzi, PO; Comi, G. Therapy of primary headaches: the role of antidepressants. Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. October 2004,. 25 Suppl 3: S171–5. PMID 15549531. doi:10.1007/s10072-004-0280-x. 
  26. ^ Tajti, J; Almási, J. [Effects of mirtazapine in patients with chronic tension-type headache. Literature review]. Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakológiai Egyesület Lapja = Official Journal of the Hungarian Association of Psychopharmacology. June 2006, 8 (2): 67–72. PMID 17073214 (匈牙利语). 
  27. ^ Kohler, M; Bloch, KE; Stradling, JR. Pharmacological approaches to the treatment of obstructive sleep apnoea. Expert Opinion on Investigational Drugs. May 2009, 18 (5): 647–56. PMID 19388881. doi:10.1517/13543780902877674. 
  28. ^ Marshall, NS; Yee, BJ; Desai, AV; Buchanan, PR; Wong, KK; Crompton, R; Melehan, KL; Zack, N; Rao, SG; Gendreau, RM; Kranzler, J; Grunstein, RR. Two randomized placebo-controlled trials to evaluate the efficacy and tolerability of mirtazapine for the treatment of obstructive sleep apnea. Sleep. June 2008, 31 (6): 824–31. PMC 2442407. PMID 18548827. 
  29. ^ Masi, G. Pharmacotherapy of pervasive developmental disorders in children and adolescents. CNS Drugs. 2004, 18 (14): 1031–52. PMID 15584771. doi:10.2165/00023210-200418140-00006. [永久失效連結]
  30. ^ Marek, GJ; Carpenter, LL; McDougle, CJ; Price, LH. Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. February 2003, 28 (2): 402–12. PMID 12589395. doi:10.1038/sj.npp.1300057. 
  31. ^ Posey, DJ; Guenin, KD; Kohn, AE; Swiezy, NB; McDougle, CJ. A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2001, 11 (3): 267–77. PMID 11642476. doi:10.1089/10445460152595586. 
  32. ^ Coskun, M; Karakoc, S; Kircelli, F; Mukaddes, NM. Effectiveness of mirtazapine in the treatment of inappropriate sexual behaviors in individuals with autistic disorder. J Child Adolesc Psychopharmacol. April 2009, 19 (2): 203–6. PMID 19364298. doi:10.1089/cap.2008.020. 
  33. ^ Kumar, R; Sachdev, PS. Akathisia and second-generation antipsychotic drugs. Current Opinion in Psychiatry. May 2009, 22 (3): 293–99. PMID 19378382. doi:10.1097/YCO.0b013e32832a16da. 
  34. ^ Hieber, R; Dellenbaugh, T; Nelson, LA. Role of mirtazapine in the treatment of antipsychotic-induced akathisia. Annals of Pharmacotherapy. June 2008, 42 (6): 841–6. PMID 18460588. doi:10.1345/aph.1K672. 
  35. ^ Graves, SM; Rafeyan, R; Watts, J; Napier, TC. Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: evidence from the bench and the bedside. Pharmacology & Therapeutics. December 2012, 136 (3): 343–353. PMC 3483434. PMID 22960395. doi:10.1016/j.pharmthera.2012.08.013. 
  36. ^ Ritsner, MS. Polypharmacy in Psychiatry Practice, Volume I. Springer Science+Business Media Dordrecht. 2013. ISBN 9789400758056. 
  37. ^ Vidal, C; Reese, C; Fischer, BA; Chiapelli, J; Himelhoch, S. Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia. Clinical Schizophrenia & Related Psychoses (Walsh Medical Media). March 2013: 1–24. ISSN 1935-1232. PMID 23491969. doi:10.3371/CSRP.VIRE.030813. 
  38. ^ Tagai, K; Nagata, T; Shinagawa, S; Tsuno, N; Ozone, M; Nakayama, K. Mirtazapine improves visual hallucinations in Parkinson's disease: a case report. Psychogeriatrics. June 2013, 13 (2): 103–107. PMID 23909968. doi:10.1111/j.1479-8301.2012.00432.x. 
  39. ^ Taylor, D; Paton, C; Shitij, K. The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. 2012. ISBN 978-0-470-97948-8. 
  40. ^ Pharmacological Interventions: 10.14. Clinical Practice Recommendations. National Collaborating Centre for Mental Health/British Psychological Society. 2010.
  41. ^ Pharmacological Interventions: Third-Generation Antidepressants: 10.8.3. Mirtazapine. National Collaborating Centre for Mental Health/British Psychological Society. 2010.
  42. ^ Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA (December 2011). "Mirtazapine versus other antidepressive agents for depression". The Cochrane Database of Systematic Reviews (12): CD006528. doi:10.1002/14651858.CD006528.pub2. PMC 4158430. PMID 22161405.
  43. ^ Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JP, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JP, Geddes JR (April 2018). "Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis". Lancet. 391 (10128): 1357–1366. doi:10.1016/S0140-6736(17)32802-7. PMC 5889788. PMID 29477251.
  44. ^ Thompson C (June 2002). "Onset of action of antidepressants: results of different analyses". Human Psychopharmacology. 17 Suppl 1: S27–32. doi:10.1002/hup.386. PMID 12404667.
  45. ^ Taylor D, Paton C, Shitij K (2012). Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: Wiley-Blackwell. ISBN 978-0-47-097948-8.
  46. ^ Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA (December 2011). "Mirtazapine versus other antidepressive agents for depression". The Cochrane Database of Systematic Reviews (12): CD006528. doi:10.1002/14651858.CD006528.pub2. PMC 4158430. PMID 22161405.
  47. ^ 47.00 47.01 47.02 47.03 47.04 47.05 47.06 47.07 47.08 47.09 47.10 47.11 Anttila SA, Leinonen EV (2001). "A review of the pharmacological and clinical profile of mirtazapine". CNS Drug Rev. 7 (3): 249–64. doi:10.1111/j.1527-3458.2001.tb00198.x. PMID 11607047.
  48. ^ Fawcett J, Barkin RL (December 1998). "Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression". Journal of Affective Disorders. 51 (3): 267–85. doi:10.1016/S0165-0327(98)00224-9. PMID 10333982.
  49. ^ Möller HJ (December 2006). "Is there evidence for negative effects of antidepressants on suicidality in depressive patients? A systematic review". European Archives of Psychiatry and Clinical Neuroscience. 256 (8): 476–96. doi:10.1007/s00406-006-0689-8. PMID 17143567.
  50. ^ Abo-Zena RA, Bobek MB, Dweik RA (April 2000). "Hypertensive urgency induced by an interaction of mirtazapine and clonidine". Pharmacotherapy. 20 (4): 476–8. doi:10.1592/phco.20.5.476.35061. PMID 10772378.
  51. ^ 《米氮平片说明书》,山德士(中国)制药有限公司。
  52. ^ 52.0 52.1 Benazzi F (June 1998). "Mirtazapine withdrawal symptoms". Canadian Journal of Psychiatry. Revue canadienne de psychiatrie. 43 (5): 525. PMID 9653542.[不可靠的醫學來源?]
  53. ^ Blier P (2001). "Pharmacology of rapid-onset antidepressant treatment strategies". The Journal of Clinical Psychiatry. 62 Suppl 15: 12–7. PMID 11444761.
  54. ^ Vlaminck JJ, van Vliet IM, Zitman FG (March 2005). "[Withdrawal symptoms of antidepressants]". Nederlands Tijdschrift Voor Geneeskunde (in Dutch and Flemish). 149 (13): 698–701. PMID 15819135.
  55. ^ Berigan TR (June 2001). "Mirtazapine-Associated Withdrawal Symptoms: A Case Report". Primary Care Companion to the Journal of Clinical Psychiatry. 3 (3): 143. doi:10.4088/PCC.v03n0307a. PMC 181176. PMID 15014614.[不可靠的醫學來源?]
  56. ^ Klesmer J, Sarcevic A, Fomari V (August 2000). "Panic attacks during discontinuation of mirtazepine". Canadian Journal of Psychiatry. Revue canadienne de psychiatrie. 45 (6): 570–1. PMID 10986577.[不可靠的醫學來源?]
  57. ^ MacCall C, Callender J (October 1999). "Mirtazapine withdrawal causing hypomania". The British Journal of Psychiatry. 175 (4): 390. doi:10.1192/bjp.175.4.390a. PMID 10789310.[不可靠的醫學來源?]
  58. ^ Ali S, Milev R (May 2003). "Switch to mania upon discontinuation of antidepressants in patients with mood disorders: a review of the literature". Canadian Journal of Psychiatry. Revue canadienne de psychiatrie. 48 (4): 258–64. doi:10.1177/070674370304800410. PMID 12776393.
  59. ^ 59.0 59.1 59.2 Timmer CJ, Sitsen JM, Delbressine LP (June 2000). "Clinical pharmacokinetics of mirtazapine". Clinical Pharmacokinetics. 38 (6): 461–74. doi:10.2165/00003088-200038060-00001. PMID 10885584.
  60. ^ Anttila SA, Leinonen EV (2001). "A review of the pharmacological and clinical profile of mirtazapine". CNS Drug Rev. 7 (3): 249–64. doi:10.1111/j.1527-3458.2001.tb00198.x. PMID 11607047.
  61. ^ "Mirtazapine Monograph for Professionals - Drugs.com".
  62. ^ Fawcett J, Barkin RL (December 1998). "Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression". Journal of Affective Disorders. 51 (3): 267–85. doi:10.1016/S0165-0327(98)00224-9. PMID 10333982.
  63. ^ Stahl SM (2008). Stahl's Essential Psychopharmacology Online: Print and Online. Cambridge, UK: Cambridge University Press. ISBN 0-521-74609-4.
  64. ^ Silva J, Mota J, Azevedo P (March 2016). "California rocket fuel: And what about being a first line treatment?". European Psychiatry. 33: S551. doi:10.1016/j.eurpsy.2016.01.2033.
  65. ^ Taylor D, Paton C, Shitij K (2012). Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: Wiley-Blackwell. ISBN 978-0-47-097948-8.
  66. ^ White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type" (PDF). Journal of Medical Toxicology. 4 (4): 238–50. doi:10.1007/bf03161207. PMC 3550116. PMID 19031375.
  67. ^ Fawcett J, Barkin RL (December 1998). "Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression". Journal of Affective Disorders. 51 (3): 267–85. doi:10.1016/S0165-0327(98)00224-9. PMID 10333982.
  68. ^ Holzbach R, Jahn H, Pajonk FG, Mähne C (November 1998). "Suicide attempts with mirtazapine overdose without complications". Biological Psychiatry. 44 (9): 925–6. doi:10.1016/S0006-3223(98)00081-X. PMID 9807651.[不可靠的醫學來源?]
  69. ^ Retz W, Maier S, Maris F, Rösler M (November 1998). "Non-fatal mirtazapine overdose". International Clinical Psychopharmacology. 13 (6): 277–9. doi:10.1097/00004850-199811000-00007. PMID 9861579.[不可靠的醫學來源?]
  70. ^ Nikolaou P, Dona A, Papoutsis I, Spiliopoulou C, Maravelias C. "Death Due to Mirtazapine Overdose". in "Abstracts of the XXIX International Congress of the European Association of Poison Centres and Clinical Toxicologists, May 12–15, 2009, Stockholm, Sweden". Clinical Toxicology. 47 (5): 436–510. 2009. doi:10.1080/15563650902952273.
  71. ^ Baselt, RC (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1045–7. ISBN 978-0-9626523-7-0.
  72. ^ Buckley NA, McManus PR (December 2002). "Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data". BMJ. 325 (7376): 1332–3. doi:10.1136/bmj.325.7376.1332. PMC 137809. PMID 12468481.[不可靠的醫學來源?]
  73. ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  74. ^ 74.0 74.1 Tatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". Eur. J. Pharmacol. 340(2–3): 249–58. doi:10.1016/s0014-2999(97)01393-9. PMID 9537821.
  75. ^ 75.00 75.01 75.02 75.03 75.04 75.05 75.06 75.07 75.08 75.09 75.10 75.11 75.12 75.13 75.14 75.15 75.16 75.17 75.18 75.19 75.20 Van der Mey M, Windhorst AD, Klok RP, Herscheid JD, Kennis LE, Bischoff F, Bakker M, Langlois X, Heylen L, Jurzak M, Leysen JE (2006). "Synthesis and biodistribution of [11C]R107474, a new radiolabeled alpha2-adrenoceptor antagonist". Bioorg. Med. Chem. 14 (13): 4526–34. doi:10.1016/j.bmc.2006.02.029. PMID 16517171.
  76. ^ 76.0 76.1 Gillman PK (2007). "Tricyclic antidepressant pharmacology and therapeutic drug interactions updated". Br. J. Pharmacol. 151 (6): 737–48. doi:10.1038/sj.bjp.0707253. PMC 2014120. PMID 17471183.
  77. ^ Tatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". Eur. J. Pharmacol. 340(2–3): 249–58. doi:10.1016/s0014-2999(97)01393-9. PMID 9537821.
  78. ^ 78.0 78.1 Van der Mey M, Windhorst AD, Klok RP, Herscheid JD, Kennis LE, Bischoff F, Bakker M, Langlois X, Heylen L, Jurzak M, Leysen JE (2006). "Synthesis and biodistribution of [11C]R107474, a new radiolabeled alpha2-adrenoceptor antagonist". Bioorg. Med. Chem. 14 (13): 4526–34. doi:10.1016/j.bmc.2006.02.029. PMID 16517171.
  79. ^ 79.0 79.1 79.2 79.3 79.4 79.5 79.6 79.7 79.8 Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA (2005). "Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents". J. Med. Chem. 48(6): 1709–12. doi:10.1021/jm049632c. PMID 15771415.
  80. ^ 80.0 80.1 Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (2012). "Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics". Naunyn Schmiedebergs Arch. Pharmacol. 385 (2): 145–70. doi:10.1007/s00210-011-0704-0. PMID 22033803.
  81. ^ 81.0 81.1 81.2 de Boer TH, Maura G, Raiteri M, de Vos CJ, Wieringa J, Pinder RM (April 1988). "Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers". Neuropharmacology. 27(4): 399–408. doi:10.1016/0028-3908(88)90149-9. PMID 3419539.
  82. ^ Gillman PK (2006). "A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status". Hum Psychopharmacol. 21 (2): 117–25. doi:10.1002/hup.750. PMID 16342227.