三叉神经痛,卡马西平效果差?轻中重度疼痛如何选药、再联用?

2022-07-05 MedSci原创 MedSci原创 发表于上海

目前,治疗 PTN 的方法很多,口服药物治疗仍为首选。

 

原发性三叉神经痛(primary trigeminal neuralgia,PTN)是一种三叉神经支配区反复发作的剧烈疼痛,发病率15.5 /10 万人,多见于中年女性,它以反复、单侧、短暂性、电击样疼痛为特点,突发突止,疼痛局限在三叉神经一个或多个分支分布范围内。严重影响患者的工作和生活。

 

 

原发性三叉神经痛病因尚未完全明了,周围学说认为病变位于半月神经节到脑桥间的部分,是由于多种原因引起的压迫所致;中枢学说认为三叉神经痛为一种感觉性癫痫样发作,异常放电部位可能在三叉神经脊束核或脑干。目前,治疗 PTN 的方法很多,口服药物治疗仍为首选。

 

 

目前 PTN 的治疗手段包括药物治疗和外科治疗。药物治疗对PTN 疗效确切,卡马西平和奥卡西平仍然是原发性三叉神经痛首选药物;拉莫三嗪、加巴喷丁、普瑞巴林、A型肉毒杆菌毒素和巴氯芬等可用作单药或多药治疗的二线治疗。

 

原发性三叉神经痛的预防性药物治疗

注:*可以以较慢的速度增加剂量以提高耐受性;剂量增加,直到疼痛得到很好的控制,显著的副作用出现或达到最大剂量。†剂量可以更缓慢地以更小的递减量减少;将剂量减少到控制疼痛所需的最低剂量或允许停药而不复发疼痛。

 


典型原发性三叉神经痛的自然恢复几乎是不可能的,药物治疗可能部分缓解疼痛或出现完全缓解与复发交替,因此,鼓励患者根据发作频率调整药物剂量。

 

1、首选卡马西平治疗
卡马西平其主要机制为可以降低脊髓三叉神经核的神经元对刺激的反应。最大剂量为1g/天,疼痛停止后维持治疗剂量两周左右,逐渐减量至最小有效维持量。该药可使69%患者可获得完全或可接受的疼痛缓解。
使用过卡马西平等药物者:

① 疼痛明显缓解或消除,无明显不良反应者,可继续使用上述药物;疼痛明显缓解或消除,但有明显不良反应者,可卡马西平减量,联合甲钴胺;

② 疼痛部分缓解,无明显不良反应者,可联用甲钴胺或卡马西平加量;疼痛部分缓解,但有明显不良反应者,可卡马西平减量,联合甲钴胺,或改用其他抗癫痫药物;

③ 疼痛未缓解,无明显不良反应者,可联用甲钴胺;疼痛未缓解,但有明显不良反应者,可卡马西平减量,联合甲钴胺;

④ 疼痛未缓解或部分缓解,伴有明显焦虑者,可联用氯硝西泮。
2、奥卡西平
奥卡西平是卡马西平的10-酮基衍生物,药效与卡马西平相似或稍强。奥卡西平及其代谢物(羟基衍生物)均具有抗惊厥活性,对大脑皮质运动有高度选择性抑制作用,其作用可能在于阻断脑细胞的电压依赖性钠通道,从而阻止病灶放电的扩布。此外,奥卡西平亦作用于钾、钙离子通道。
奥卡西平主要用于对卡马西平有过敏反应者,可作为卡马西平的替代药物应用临床。用于不耐受卡马西平或用其治疗无效的三叉神经痛。为了获得理想的效果,可以每隔一个星期增加每天的剂量,每次增加剂量不要超过600mg。每日维持剂量范围一般有效药物剂量为每日1200mg。
3、加巴喷丁
加巴喷丁是一种新颖的抗癫痫药,它是γ-氨基丁酸(GABA)的衍生物,其药理作用与现有的抗癫痫药不同。加巴喷丁在结构上与神经递质GABA相关,但不与GABA受体产生相互作用,它既不能代谢转化为GABA或GABA激动剂,也不是GABA摄取或降解的抑制剂。
近年国内临床研究,结果认为巴喷丁治疗原发性三叉神经痛的疗效优于卡马西平,且安全性更高,与卡马西平相比,认为加巴喷丁不仅在血浆β-EP(β内啡肽)含量升高及SP(P物质)含量下降方面较为明显,而且在临床有效及安全性方面也优于卡马西平。
4、拉莫三嗪
拉莫三嗪对三叉神经痛和中枢痛有效,其机制为通过阻断电压依赖性钠通道和抑制周围产生神经异位冲动的产生,减少中枢谷氨酸和天门冬谷氨酸等兴奋性递质的释放。临床观察证明,拉莫三嗪治疗原发性三叉神经痛短期疗效显著,不良反应较少,且在有效患者中完全缓解的可能性较大,可作为治疗原发性三叉神经痛的常用药物。
5. 甲钴胺
 
强烈推荐用于 PTN 的治疗。可促进卵磷脂的合成和神经元髓鞘形成,对轴突再生、促进神经生长产生较强的刺激,对缓解神经痛有一定作用,能改善临床症状。不良反应包含偶有恶心、呕吐、食欲不振、腹泻。
甲钴胺片:口服,0.5 mg/次,3 次/d 。
甲钴胺注射液:肌肉注射,0.5 mg/次,1 次/隔日,连续 10 次。可按年龄、症状酌情增减。
6. B 族维生素
如维生素 B1 、维生素 B12、复合维生素 B。可保护和防止神经脱髓鞘改变和促进神经功能恢复,对缓解神经痛有一定作用,能改善临床症状。维生素 B1 和维生素 B12 或复合维生素 B 片,口服,1 片/次,3 次/d 。维生素 B1 注射液 100 mg、维生素 B12 注射液 1 mg,或复合维生素 B 注射液 100 mg ,肌注,1 次/d ,连续 10 次。大剂量服用可引起食欲减退、烦躁、疲倦、瘙痒等。

原发性三叉神经痛不同疼痛程度的药物推荐


1、轻度疼痛可选用卡马西平/奥卡西平;

2、中度疼痛可选用卡马西平/奥卡西平 + 氨酚羟考酮;普瑞巴林 + 氨酚羟考酮(卡马西平无效或禁忌)

3、重度疼痛可选用三叉神经阻滞 + 卡马西平/奥卡西平/普瑞巴林;氨酚羟考酮口服/曲马多口服/吗啡注射。
对于急性加重期的疼痛,有必要住院治疗来调整抗癫痫药的剂量以及静脉使用磷苯妥英和利多卡因。
对于缓解长期疼痛,尤其是针对早期的三叉神经痛患者,卡马西平(200-1200 mg/天)或者奥卡西平(300-1800 mg/天)是最有效的治疗药物。且有时可采用更高的剂量。

预后

 
原发性三叉神经痛的特点是复发和缓解。治疗目的是有效缓解疼痛,改善患者的生活质量,避免并发症及严重不良事件的发生。目前指南推荐一线治疗是药物治疗,需要充分考虑药物的疗效、安全性、相互作用以及患者的耐受性、经济条件等多个因素。
建议优先使用卡马西平或奥卡西平,根据患者实际情况调整方案或联合其它药物治疗,但联合用药的临床研究很少,仍需进一步探索。我们应当鼓励患者根据疼痛严重程度或者药物的副作用来调整药物剂量。告知患者逐日缓慢增减药物剂量是非常重要的。
当药物治疗的疗效减退或者出现患者无法耐受的药物不良反应而导致药物治疗失败时,可以尽早考虑外科手术治疗。目前外科治疗方法主要包括经皮三叉神经半月节射频热凝术、Meckel囊球囊压迫术、立体定向伽马刀放射治疗和微血管减压术。

参考文献:

[1] Patel SK, Liu JK. Overview and History of Trigeminal Neuralgia[J]. Neurosurgery Clinics of North America, 2016, 27(3):265.
[2] Ou GJ, Wang J, Ji X, et al. A study of HLA-B*15:02 in 9 different Chinese ethnics:Implications for carbamazepine related SJS/TEN[J]. HLA,2017,89:225–229.
[3] Bendtsen L, Zakrzewska J M, Abbott J, et al. EAN guideline on trigeminal neuralgia[J]. European journal of neurology, 2019.
[4]中国三叉神经痛伽玛刀放射外科治疗专家共识(2020版)[J].中华神经外科杂志,2020,36(10):984.
[5] 非创伤性软组织疼痛急诊管理专家共识(2022)[J].中国急救医学,2022,42(3):197-203.
[6] 原发性三叉神经痛中西医非手术诊疗方法的专家共识[J].实用口腔医学杂志, 2022,38(2):149-160.
[7] Donnet A,Simon E, Cuny E, et al. French guidelines for diagnosis and treatment of classical trigeminal neuralgia[J]. Revue neurologique, 2017,173(3):131-151.

撰文:Dr.Wu彤

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    收藏可

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    2022-07-07 huaguang

    拉莫三嗪治疗三叉神经痛效果可以

    0

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    2022-07-07 贵阳