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Article(id=1207314223588286501, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1207314214872518754, articleNumber=null, orderNo=null, doi=10.14109/j.cnki.xyylc.2025.04.12, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1658678400000, receivedDateStr=2022-07-25, revisedDate=null, revisedDateStr=null, acceptedDate=1739721600000, acceptedDateStr=2025-02-17, onlineDate=1765775741707, onlineDateStr=2025-12-15, pubDate=1745510400000, pubDateStr=2025-04-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1765775741707, onlineIssueDateStr=2025-12-15, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1765775741707, creator=13701087609, updateTime=1765775741707, updator=13701087609, issue=Issue{id=1207314214872518754, tenantId=1146029695717560320, journalId=1205117082300743687, year='2025', volume='44', issue='4', pageStart='241', pageEnd='320', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=0, createTime=1765775739638, creator=13701087609, updateTime=1765775882010, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1207314812124635584, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1207314214872518754, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1207314812124635585, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1207314214872518754, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=315, endPage=320, ext={EN=ArticleExt(id=1207314225903542320, articleId=1207314223588286501, tenantId=1146029695717560320, journalId=1205117082300743687, language=EN, title=Literature case analysis of dextromethorphan-induced 5-hydroxytryptamine syndrome, columnId=1207314224800440367, journalTitle=Chinese Journal of New Drugs and Clinical Remedies, columnName=Pharmacovigilance, runingTitle=null, highlight=null, articleAbstract=

AIM To analyze the clinical characteristics and influencing factors of dextromethorphan-induced 5-hydroxytryptamine syndrome （5-HTS）. METHODS Relevant cases of dextromethorphan-induced 5-HTS in PubMed,Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, WanFang database, SinoMed, and VIP database were retrieved,and clinical data were summarized and analyzed. RESULTS A total of 16 cases of 5-HTS were collected, including 11 males and 5 females. Dextromethorphan could cause 5-HTS at both normal and excessive doses, and the majority （88%）of patients were co-administered with other 5-hydroxytryptamine drugs. The onset of 5-HTS occurred between 4 hours and 6 weeks after dextromethorphan administration, with symptoms including myoclonus, tachycardia, and fever. After discontinuation of dextromethorphan and other serotonergic drugs, along with supportive therapy, all patients improved.The mean duration of 5-HTS was 26 hours. Patients treated with cyproheptadine had a shorter duration of 5-HTS, averaging 21.6 hours. CONCLUSION Dextromethorphan-induced 5-HTS most often occurs when used in combination with other serotonergic drugs. It is recommended to strengthen management to reduce the abuse of dextromethorphan and unnecessary co-administration, as well as to improve the ability of physicians and pharmacists to recognize and monitor 5-HTS.

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目的 分析右美沙芬致5-羟色胺综合征（5-HTS）的临床特征和影响因素。方法 系统检索PubMed、Embase、Cochrane Library、CINAHL、PsycINFO、中国知网、万方数据、中国生物医学文献数据库和维普网等中英文数据库，收集右美沙芬致5-HTS的相关病例，对其临床资料进行汇总分析。结果 共收集到16例5-HTS病例，男性11例，女性5例。右美沙芬剂量正常或过量均可引起5-HTS。绝大多数（88%）患者联用了5-羟色胺能药物。5-HTS的发生时间为使用右美沙芬4 h~6周后，主要表现为肌阵挛、心动过速、发热等。停用右美沙芬和其他5-HT能药物，或进行支持治疗后患者均好转，5-HTS平均持续时间为26 h。使用赛庚啶治疗的患者5-HTS持续时间更短，为21.6 h。结论 右美沙芬致5-HTS多在与其他5-HT能药物联合使用时发生。建议进一步加强管理，减少该药滥用及不必要的联合用药，并提升医师和药师对5-HTS的识别和用药监护能力。

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张青霞
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邓健浩，男，主管药师，硕士，主要从事药物过量与药物不良反应的研究，E-mail: 。

张青霞，女，副主任药师，硕士，主要从事临床药学与用药安全的研究，E-mail:

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邓健浩，男，主管药师，硕士，主要从事药物过量与药物不良反应的研究，E-mail: 。

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邓健浩，男，主管药师，硕士，主要从事药物过量与药物不良反应的研究，E-mail: 。

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张青霞，女，副主任药师，硕士，主要从事临床药学与用药安全的研究，E-mail:

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张青霞，女，副主任药师，硕士，主要从事临床药学与用药安全的研究，E-mail:

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序号第一作者和发表时间患者性别患者年龄/岁右美沙芬用药原因基础疾病用法用量联用的5-HT能药物联合用药至发病时间5-HTS的临床表现对症治疗药物转归时间/h
1OMOTO 2022 [10]女23滥用双相情感障碍1.8 g，单次米氮平4 h①②③赛庚啶24
2PRAKASH 2021[11]男21上呼吸道感染双相情感障碍15 mg，tid，2周艾司西酞普兰、利培酮、曲马
多、昂丹司琼		48 h①②③劳拉西泮、赛庚啶12
3BACHAR 2021[12]女31滥用焦虑30 mg，bid，4周氯苯那敏*6周①②丙泊酚、芬太尼、咪达唑仑24
4HARDY 2020[13]女68上呼吸道感染双相情感障碍15 mg，tid，3 d度洛西汀、米氮平、曲唑酮和曲马多/②③无48
5DY 2017[14]女63上呼吸道感染抑郁15 mg，tid，2周艾司西酞普兰、异丙嗪9 d①②③赛庚啶12
6KELSEY 2016[15]男19逆转甲氨蝶呤的神经毒性肿瘤80 mg，单次无/①②③劳拉西泮、赛庚啶48
7SASAKI 2013[16]女65上呼吸道感染抑郁15 mg，tid，3 d马普替林3 d②③赛庚啶、咪达唑仑/
8SETHI 2012[17]男46上呼吸道感染抑郁160 mg，单次舍曲林1 d①②③地西泮48
9KINOSHITA 2011[18]男77上呼吸道感染慢性肝肾功能不全15 mg，tid，4 d无4 d②③无72
10MONTE 2010[19]男19自杀双相情感障碍1 440 mg，单次氯苯那敏*12 h②③劳拉西泮6
11SCHWARTZ 2008[20]男20自杀抑郁/艾司西酞普兰、阿立哌唑、氯苯那敏*/①②③劳拉西泮、赛庚啶12
12SCHWARTZ 2008[20]男6滥用/800 mg，单次舍曲林/①②③/15
13KUNG 2007[21]男29上呼吸道感染急性胃肠炎/曲马多、甲氧氯普胺、吗啡4 h①②③地西泮、咪达唑仑6
14GANETSKY 2007[22]男18滥用无480 mg，单次氯苯那敏*/①②③劳拉西泮、丙泊酚10
15NAVARRO 2006[23]男22滥用双相情感障碍/氟西汀/①②③劳拉西泮、普萘洛尔/
16SKOP 1994[24]男51上呼吸道感染抑郁/帕罗西汀2 d①②③劳拉西泮/
), ArticleFig(id=1207314233025470702, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1207314223588286501, language=CN, label=表1, caption=

右美沙芬致5-羟色胺综合征（5-HTS）的患者资料

, figureFileSmall=null, figureFileBig=null, tableContent=
序号第一作者和发表时间患者性别患者年龄/岁右美沙芬用药原因基础疾病用法用量联用的5-HT能药物联合用药至发病时间5-HTS的临床表现对症治疗药物转归时间/h
1OMOTO 2022 [10]女23滥用双相情感障碍1.8 g，单次米氮平4 h①②③赛庚啶24
2PRAKASH 2021[11]男21上呼吸道感染双相情感障碍15 mg，tid，2周艾司西酞普兰、利培酮、曲马
多、昂丹司琼		48 h①②③劳拉西泮、赛庚啶12
3BACHAR 2021[12]女31滥用焦虑30 mg，bid，4周氯苯那敏*6周①②丙泊酚、芬太尼、咪达唑仑24
4HARDY 2020[13]女68上呼吸道感染双相情感障碍15 mg，tid，3 d度洛西汀、米氮平、曲唑酮和曲马多/②③无48
5DY 2017[14]女63上呼吸道感染抑郁15 mg，tid，2周艾司西酞普兰、异丙嗪9 d①②③赛庚啶12
6KELSEY 2016[15]男19逆转甲氨蝶呤的神经毒性肿瘤80 mg，单次无/①②③劳拉西泮、赛庚啶48
7SASAKI 2013[16]女65上呼吸道感染抑郁15 mg，tid，3 d马普替林3 d②③赛庚啶、咪达唑仑/
8SETHI 2012[17]男46上呼吸道感染抑郁160 mg，单次舍曲林1 d①②③地西泮48
9KINOSHITA 2011[18]男77上呼吸道感染慢性肝肾功能不全15 mg，tid，4 d无4 d②③无72
10MONTE 2010[19]男19自杀双相情感障碍1 440 mg，单次氯苯那敏*12 h②③劳拉西泮6
11SCHWARTZ 2008[20]男20自杀抑郁/艾司西酞普兰、阿立哌唑、氯苯那敏*/①②③劳拉西泮、赛庚啶12
12SCHWARTZ 2008[20]男6滥用/800 mg，单次舍曲林/①②③/15
13KUNG 2007[21]男29上呼吸道感染急性胃肠炎/曲马多、甲氧氯普胺、吗啡4 h①②③地西泮、咪达唑仑6
14GANETSKY 2007[22]男18滥用无480 mg，单次氯苯那敏*/①②③劳拉西泮、丙泊酚10
15NAVARRO 2006[23]男22滥用双相情感障碍/氟西汀/①②③劳拉西泮、普萘洛尔/
16SKOP 1994[24]男51上呼吸道感染抑郁/帕罗西汀2 d①②③劳拉西泮/
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右美沙芬致5-羟色胺综合征的文献病例分析
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邓健浩 1 , 邱德胜 1 , 张青霞 1, 2
中国新药与临床杂志 | 药物警戒 2025,44(4): 315-320
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中国新药与临床杂志 | 药物警戒 2025, 44(4): 315-320
右美沙芬致5-羟色胺综合征的文献病例分析
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邓健浩1 , 邱德胜1, 张青霞1, 2
作者信息
  • 1.龙岩市第二医院，福建　龙岩　364000
  • 2.首都医科大学宣武医院　药学部/国家老年疾病临床医学研究中心，北京　100053

    • 邓健浩，男，主管药师，硕士，主要从事药物过量与药物不良反应的研究，E-mail: 。

    张青霞，女，副主任药师，硕士，主要从事临床药学与用药安全的研究，E-mail:

通讯作者:

张青霞
Literature case analysis of dextromethorphan-induced 5-hydroxytryptamine syndrome
Jian-hao DENG1 , De-sheng QIU1, Qing-xia ZHANG1, 2
Affiliations
  • 1. Second Hospital of Longyan City, Longyan FUJIAN 364000, China
  • 2. Department of Pharmacy, Xuanwu Hospital of Capital Medical University/National Clinical Research Center for Geriatric Diseases, BEIJING 100053, China
出版时间: 2025-04-25 doi: 10.14109/j.cnki.xyylc.2025.04.12
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摘要
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目的 分析右美沙芬致5-羟色胺综合征（5-HTS）的临床特征和影响因素。方法 系统检索PubMed、Embase、Cochrane Library、CINAHL、PsycINFO、中国知网、万方数据、中国生物医学文献数据库和维普网等中英文数据库，收集右美沙芬致5-HTS的相关病例，对其临床资料进行汇总分析。结果 共收集到16例5-HTS病例，男性11例，女性5例。右美沙芬剂量正常或过量均可引起5-HTS。绝大多数（88%）患者联用了5-羟色胺能药物。5-HTS的发生时间为使用右美沙芬4 h~6周后，主要表现为肌阵挛、心动过速、发热等。停用右美沙芬和其他5-HT能药物，或进行支持治疗后患者均好转，5-HTS平均持续时间为26 h。使用赛庚啶治疗的患者5-HTS持续时间更短，为21.6 h。结论 右美沙芬致5-HTS多在与其他5-HT能药物联合使用时发生。建议进一步加强管理，减少该药滥用及不必要的联合用药，并提升医师和药师对5-HTS的识别和用药监护能力。

右美沙芬  /  5-羟色胺综合征  /  药物滥用  /  病例分析

AIM To analyze the clinical characteristics and influencing factors of dextromethorphan-induced 5-hydroxytryptamine syndrome （5-HTS）. METHODS Relevant cases of dextromethorphan-induced 5-HTS in PubMed,Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, WanFang database, SinoMed, and VIP database were retrieved,and clinical data were summarized and analyzed. RESULTS A total of 16 cases of 5-HTS were collected, including 11 males and 5 females. Dextromethorphan could cause 5-HTS at both normal and excessive doses, and the majority （88%）of patients were co-administered with other 5-hydroxytryptamine drugs. The onset of 5-HTS occurred between 4 hours and 6 weeks after dextromethorphan administration, with symptoms including myoclonus, tachycardia, and fever. After discontinuation of dextromethorphan and other serotonergic drugs, along with supportive therapy, all patients improved.The mean duration of 5-HTS was 26 hours. Patients treated with cyproheptadine had a shorter duration of 5-HTS, averaging 21.6 hours. CONCLUSION Dextromethorphan-induced 5-HTS most often occurs when used in combination with other serotonergic drugs. It is recommended to strengthen management to reduce the abuse of dextromethorphan and unnecessary co-administration, as well as to improve the ability of physicians and pharmacists to recognize and monitor 5-HTS.

dextromethorphan  /  5-hydroxytryptamine syndrome  /  drug abuse  /  literature case analysis
邓健浩, 邱德胜, 张青霞. 右美沙芬致5-羟色胺综合征的文献病例分析. 中国新药与临床杂志, 2025 , 44 (4) : 315 -320 . DOI: 10.14109/j.cnki.xyylc.2025.04.12
Jian-hao DENG, De-sheng QIU, Qing-xia ZHANG. Literature case analysis of dextromethorphan-induced 5-hydroxytryptamine syndrome[J]. Chinese Journal of New Drugs and Clinical Remedies, 2025 , 44 (4) : 315 -320 . DOI: 10.14109/j.cnki.xyylc.2025.04.12
正文
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5-羟色胺综合征（5-hydroxytryptamine syndrome，5-HTS）又称血清素综合征或5-羟色胺中毒，是一种严重的药源性疾病[1] ，患者通常表现为精神状态改变、自主神经过度活跃和神经肌肉异常的三联征[2]。5-HTS的发生与多种机制相关，如5-羟色胺（5-hydroxytryptamine，5-HT）的合成或释放增加、5-HT受体激动或5-HT的再摄取受到抑制等[3]。尽管5-HTS可能危及生命，但有调查发现，仍有超过85%的临床医生不知道5-HTS[4]，超过90%的神经内科医生对致5-HTS的药物认识不足[5]。
右美沙芬是可待因合成类似物左啡诺的右旋异构体，主要通过抑制延脑的咳嗽中枢而发挥镇咳作用[6]。与吗啡相比，右美沙芬在治疗剂量下无成瘾性及明显的呼吸抑制作用，故被认为是最安全的镇咳药[7] 。由于该药较易获得，因而常被非法使用。在美国，每年约有100万少年和年轻成人滥用含右美沙芬的非处方咳嗽和感冒药[8] 。国内也有右美沙芬滥用的相关报道[9] 。该药引起5-HTS的病例在国外时有报道，但未见国内有相关报道。为提高国内医护人员及相关用药人群对右美沙芬致5-HTS的警觉性，本研究收集了国外文献报道的右美沙芬致5-HTS的相关病例，并进行汇总分析，以期为临床救治和合理使用该药提供参考。
资料与方法
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文献检索方法
系统检索PubMed、Embase、Cochrane Library、CINAHL、PsycINFO、中国知网、万方数据、中国生物医学文献数据库和维普网等中英文数据库，收集右美沙芬致5-HTS的相关病例报道。同时，检索毒理学会议相关的论文数据库进行补充，如北美临床毒理学大会（the North American Congress of Clinical Toxicology，NACCT）会议论文集、欧洲毒物中心和临床毒理家协会（the European Association of Poison Centers and Clinical Toxicologists，EAPCCT）会议论文集等。采用主题词与自由词相结合的方式进行检索，中文检索词包括“右美沙芬”“5-羟色胺中毒”“5-HT”“5-羟色胺综合征”“血清素综合征”等，英文检索词包括“dextromethorphan”“serotonin toxicity”“5-HT”“5-hydroxy-tryptamine syndrome”“serotonin syndrome”。检索时限均从各个数据库建库到2023年12月30日，语种不限。
文献纳入与排除标准
本研究的文献纳入标准为：经纳入文献的作者证实患者的5-HTS与右美沙芬有关的病例报告或病例系列报告。文献排除标准：（1）临床资料不完整或无法获取的文献；（2）重复发表的文献；（3）动物研究。
文献筛选和资料提取
由2位研究者按照纳入与排除标准进行文献筛选和资料提取，如遇分歧由所有研究者共同讨论解决。采用自行设计的Excel数据提取表记录纳入文献的以下信息：患者基本情况（性别、年龄、基础疾病等），右美沙芬和5-HT能药物用药情况（用药原因、用法用量），5-HTS发生情况（发生时间、临床表现），处置及转归情况（辅助检查结果、转归时长和治疗方案）等。对收集到的数据进行描述性统计分析。
结果
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文献检索结果
检索到符合条件的文献病例15篇[10-24]，包括14篇期刊论文[10-14,16-24]，1篇会议论文[15]，文献筛选流程见图1。
患者的一般情况
15篇文献共涉及16例患者，其中男性11例（69%），女性5例（31%）；年龄为6~77岁，中位年龄为29岁，以18~32岁者居多（9例，56%）。患者的基础疾病多样，包括双相情感障碍（5例，31%）、抑郁（5例，31%）、慢性肾炎、急性胃肠炎、原发性肿瘤等。见表1。
用药情况
16例患者的用药情况见表1。16例患者中，有8例患者使用右美沙芬治疗上呼吸道感染引起的咳嗽，5例是因右美沙芬成瘾导致的滥用，2例是故意服用该药自杀，1例是用于逆转甲氨蝶呤鞘内注射引起的神经毒性。16例患者使用右美沙芬的日剂量为45 mg~1.8 g，右美沙芬正常日剂量（<90 mg）或过量均可引起5-HTS。右美沙芬单药或联合5-HT能药物均可发生5-HTS。2例患者使用右美沙芬单药，其中1例患者为合并有慢性肾病的高龄患者，连续使用右美沙芬15 mg，tid治疗4 d；另1例患者合并有肿瘤，单次使用右美沙芬80 mg。14例患者（88%）联用了5-HT能药物，包括5-HT选择性再摄取抑制剂（serotonin-selective reuptake inhibitor，SSRI）艾司西酞普兰3例、舍曲林2例、帕罗西汀1例、氟西汀1例，抗组胺药氯苯那敏4例，四环类抗抑郁药米氮平2例、曲唑酮1例，5-HT受体激动剂曲马多3例、甲氧氯普胺1例、昂丹司琼1例，5-HT去甲肾上腺素再摄取抑制剂（serotonin-norepinephrine reuptake inhibitors，SNRI）度洛西汀1例，三环类抗抑郁药（tricyclic antidepressant，TCA）马普替林1例和单胺氧化酶抑制剂（monoamine oxidase inhibitor，MOI）异丙嗪1例。
5-HTS的发生情况
10例（63%）患者报告了使用右美沙芬至发生5-HTS的时间，为4 h~6周，其中，4例患者的发生时间≤1 d，3例患者的发生时间>1~3 d，3例患者的发生时间>3 d。11例（69%）患者表现为精神状态改变、自主神经过度活跃和神经肌肉异常的三联征，4例（25%）患者表现为自主神经过度活跃和神经肌肉异常的二联征，1例（6%）患者表现为精神状态改变和自主神经过度活跃的二联征。其中，精神状态改变包括躁动（6例）、激越（5例）、意识混乱（5例）、嗜睡（2例）和昏迷（1例）；自主神经过度活跃包括心动过速（12例）、发热（10例）、出汗（9例）、血压升高（8例）、瞳孔散大（4例）、肠鸣音亢进（3例）、QT间期延长（3例）、心律失常（1例）、Takotsubo心肌病（1例）、低血压（1例）、腹部疼痛（1例）和腹泻（1例）；神经肌肉异常包括肌阵挛（14例）、反射亢进（7例）、震颤（5例）、肌肉僵硬（5例）、眼阵挛（4例）、静坐不能（2例）、张力过高（2例）及双侧巴宾斯基征阳性、共济失调和四肢抽搐各1例。此外，还有8例患者出现白细胞升高（患者2、5、6、7、11、13、15、16），3例患者出现代谢性酸中毒（患者5、8、13），患者2同时并发神经阻滞剂恶性综合征，患者3同时诱发了既往的精神分裂症。
处置及转归
8例患者进行了神经系统检查，其中7例进行了脑部CT检查，1例进行了脑部核磁共振检查；5例同时进行了脑电图检查；4例同时进行了脑脊液检查，结果均无异常。16例患者明确5-HTS后均停用了右美沙芬和其他5-HT能药物，或进行了对症支持治疗：11例给予苯二氮䓬类药物进行镇静，6例给予赛庚啶进行5-HT拮抗。提供了5-HTS转归时间的13例患者，5-HTS转归时间从6 h到72 h不等，平均26 h，其中大部分患者（9例）可在1 d内恢复正常；使用赛庚啶进行处理的患者5-HTS持续时间平均为21.6 h，短于未使用赛庚啶进行处理的患者（28.6 h），表明使用赛庚啶进行5-HT拮抗的效果较好。16例患者均经对症治疗后好转出院，预后良好，无并发症。
讨论
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因大剂量右美沙芬具有兴奋和解离作用，在国外青少年群体中存在滥用的现象[8] 。本研究显示，右美沙芬致5-HTS的男性占比多于女性，且以18~32岁居多，这可能与该类药物在男性青少年中广泛滥用有关[25]。在美国，每年因非医疗原因使用右美沙芬前往急诊就诊的患者将近6 000例次，其中半数为青少年和年轻成人[26]。
根据国家药品监督管理局关于氢溴酸右美沙芬口服单方制剂转换为处方药的公告（2021年第151号）要求，服用MOI（如利奈唑胺）、SSRI（如氟西汀、帕罗西汀）、安非他酮等药物的患者在开始使用右美沙芬前至少需要2周的药物洗脱期。纳入本研究的16例患者中，联合用药的14例患者均未进行药物洗脱，表明医务工作者对右美沙芬致5-HTS的认识不足。其中，9例患者联用了SSRI、SNRI、TCA等药物，其5-HTS可能与这些药物对神经传递的影响有关[27]。16例患者中，有4例患者联用了氯苯那敏。氯苯那敏为第一代H1组胺受体拮抗剂，该药是否会增加5-HTS的风险尚存在争议。有研究表明，氯苯那敏可能是一种5-HT能药物，其对5-HT受体具有高度亲和力，并能有效抑制5-HT的再摄取[28]。考虑到氯苯那敏和右美沙芬常作为复方感冒药或止咳药物的成分之一，医务工作者要时刻警惕两种药物长期合用导致体内蓄积或过量滥用时致5-HTS的风险。2例患者未联用其他药物，在正常剂量右美沙芬下出现5-HTS，可能与其本身肾功能衰竭导致右美沙芬排泄减少，且高龄患者易发生不良反应有关[18]。
其他药物所致5-HTS通常在剂量增加或加用5-HT能药物后2 h内出现，67%的患者是在6 h内出现症状，75%的患者是在24 h内出现症状[29, 30]。而本研究结果显示，服用右美沙芬后发生5-HTS的时间介于4 h~6周，可能与右美沙芬是弱SSRI，5-HT的蓄积需要较长的时间，以及诱导期较长有关[31]。5-HTS的诊断主要依据临床表现和既往用药史。目前诊断5-HTS的金标准是Hunter标准，即患者使用5-HT能药物后出现以下情况之一：（1）自发性阵挛；（2）诱导性阵挛伴激越状态或出汗；（3）视性眼阵挛伴激越状态或出汗；（4）震颤伴反射亢进；（5）张力过高伴发热，合并有眼阵挛或诱导性阵挛[32]。本研究中，右美沙芬致5-HTS的主要临床表现为肌阵挛、心动过速、发热、出汗、血压升高、反射亢进等，症状较为典型，与利奈唑胺、曲马多等其他药物引起的5-HTS症状有所不同[33-35]。
5-HTS的治疗包括停用右美沙芬及所有5-HT能药物，提供对症支持治疗（供氧、心电监护、静脉补液、镇静和纠正生命征异常），必要时采用5-HT拮抗剂（如赛庚啶）[26]。赛庚啶是H1组胺受体拮抗剂，有较弱的抗胆碱能活性，对5-HT1A和5-HT2A也有非特异性的拮抗作用[36]。赛庚啶治疗5-HTS的有效性尚存在争议。NGUYEN等[37]在一项回顾性研究中发现，使用或不使用赛庚啶治疗5-HTS，患者结局无显著差异。然而，也有很多报道称赛庚啶成功治疗了5-HTS[36]。本研究显示，使用赛庚啶治疗的患者5-HTS平均持续时间短于未使用赛庚啶的患者。结合赛庚啶的有效性、安全性、经济性和可及性，笔者建议，在无禁忌证的情况下，发生5-HTS时临床可以考虑使用赛庚啶进行治疗。本研究中右美沙芬致5-HTS的平均持续较短，为26 h，这可能与右美沙芬的半衰期短（3 h）有关[7]。
为预防右美沙芬相关的5-HTS，建议各级卫生部门应首先防范该药的滥用问题。本研究中，有1/3（6例）病例为滥用右美沙芬者。右美沙芬既往为非处方药，使用者可以不凭借处方直接在药店购得。虽然我国国家药品监督管理局已将其纳入处方药管理，并删除了该药说明书中“长期服用无成瘾性和耐受性”的描述[27]，但仍建议相关部门进一步加强管制，并对青少年进行合理用药宣传教育，增强其自我防范意识。另外，还应加强医师和药师对5-HTS认识的培训。医师在开具右美沙芬时应充分了解患者的基础疾病、合并用药及用药史，对于高风险人群可考虑选用其他药物替代治疗；在无其他药物可替代的情况下宜开具最低有效剂量，严密监护患者服药后3 d的病情变化，并对患者进行5-HTS的用药教育。由于部分患者合并多种疾病，常同时就诊于多个科室，医师无法识别患者当前服用的其他药物，因此有必要加强处方信息系统的预警作用（如前置审方），还要加强药师的审方能力，及时审核并干预多处方中5-HT能类药物相互作用的情况。此外，还应教育患者避免同时服用一些可能致5-HTS的非处方药和草药，如人参、圣约翰草等。
基金
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  • 国家重点研发计划资助(2020YFC2008305)
  • 北京市科学技术委员会“北京老年人健康评估及维护关键技术研究”项目(D181100000218002)
文献
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2025年第44卷第4期
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doi: 10.14109/j.cnki.xyylc.2025.04.12
  • 接收时间：2022-07-25
  • 首发时间：2025-12-15
  • 出版时间：2025-04-25
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  • 收稿日期：2022-07-25
  • 录用日期：2025-02-17
基金
国家重点研发计划资助(2020YFC2008305)
北京市科学技术委员会“北京老年人健康评估及维护关键技术研究”项目(D181100000218002)
作者信息
    1.龙岩市第二医院，福建　龙岩　364000
    2.首都医科大学宣武医院　药学部/国家老年疾病临床医学研究中心，北京　100053

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张青霞
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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