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Recurrence of suicidal ideation due to treatment with antidepressants in anxiety disorder a case report 用抗抑郁药治疗焦虑症导致自杀意念再次出现 病例报告.doc

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Recurrence of suicidal ideation due to treatment with antidepressants in anxiety disorder a case report 用抗抑郁药治疗焦虑症导致自杀意念再次出现 病例报告.doc

RECURRENCEOFSUICIDALIDEATIONDUETOTREATMENTWITHANTIDEPRESSANTSINANXIETYDISORDERACASEREPORT用抗抑郁药治疗焦虑症导致自杀意念再次出现病例报告DORONTODDER1ANDBERNHARDTBAUNE2,31DEPARTMENTOFPSYCHIATRY,BENGURIONUNIVERSITY,BEERSHEVA,ISRAEL2DEPARTMENTOFPSYCHIATRY,UNIVERSITYOFMUENSTER,GERMANY3DEPARTMENTOFPSYCHIATRY,JAMESCOOKUNIVERSITY,AUSTRALIAAUTHOREMAILCORRESPONDINGAUTHOREMAILJOURNALOFMEDICALCASEREPORTS2007,1166DOI101186/175219471166THEELECTRONICVERSIONOFTHISARTICLEISTHECOMPLETEONEANDCANBEFOUNDONLINERECEIVED3SEPTEMBER2007ACCEPTED3DECEMBER2007PUBLISHED3DECEMBER20072007TODDERANDBAUNE;LICENSEEBIOMEDCENTRALLTDTHISISANOPENACCESSARTICLEDISTRIBUTEDUNDERTHETERMSOFTHECREATIVECOMMONSATTRIBUTIONLICENSEWHICHPERMITSUNRESTRICTEDUSE,DISTRIBUTION,ANDREPRODUCTIONINANYMEDIUM,PROVIDEDTHEORIGINALWORKISPROPERLYCITEDABSTRACT摘要THISREPORTDESCRIBESAPATIENTSUFFERINGFROMPANICDISORDERWHODEVELOPEDREPEATEDSUICIDALIDEATIONSPECIFICALLYDUETOTHETREATMENTWITHVENLAFAXINEAFIRSTSUICIDEATTEMPTYEARSAGOOCCURREDWHILEBEINGTREATEDWITHVENLAFAXINESUBSEQUENTTREATMENTWITHSSRISOROTHERANTIDEPRESSANTSINVOLVEDNOSUICIDALIDEATIONRECOMMENCEMENTOFVENLAFAXINEFOURYEARSLATERIMMEDIATELYLEDTOASECONDSUICIDEATTEMPTTHISUNWANTEDEFFECTSUBSIDEDIMMEDIATELYAFTERSWITCHINGTOANOTHERSNRIIEDULOXETINETHECASEREPORTUNDERLINESTHEIMPORTANCEOFONSETOFSUICIDERISKINPANICDISORDERSDUETOSPECIFICANTIDEPRESSANTS本报告描述的是一名惊恐障碍患者反复出现由文拉法辛治疗特定导致的自杀意念。患者数年前用文拉法辛治疗时首次出现自杀企图。后来用SSRI(选择性5羟色胺再摄取抑制剂)或其他抗抑郁药未出现自杀意念。4年后重新开始用文拉法辛治疗,随即导致了第二次自杀企图。将药物更换为另一种SNRI(选择性去甲肾上腺素再摄取抑制剂)(度洛西汀)后,此副作用迅速消退。本病例报告强调了治疗惊恐障碍时,特效抗抑郁药导致出现自杀风险的重要性。INTRODUCTION引言SINCETHEINTRODUCTIONOFTHEFIRSTSPECIFICSEROTONINREUPTAKEINHIBITORSSSRIFLUOXETINE,ACONCERNEMERGEDREGARDINGTHERISKOFDEVELOPINGSUICIDEIDEATIONASARARESIDEEFFECT1DURING2003,BRITAINSCOMMITTEEONSAFETYOFMEDICINESISSUEDAWARNINGABOUTTHEDANGERSOFDEVELOPINGSUICIDEASSIDEEFFECT,FIRSTFORPAROXETINEANDTHENEXTENDEDTHEWARNINGTOALLTHENEWANTIDEPRESSANTS2THEUSAFOODANDDRUGADMINISTRATIONFOLLOWED,EMBRACINGTHEWARNINGFORCHILDREN,ANDTHENEXTENDEDTHEWARNINGTOADULTS3由于首个特效5羟色胺再摄取抑制剂SSRI氟西汀的出现,人们开始担心会出现自杀意念这一罕见副作用的风险1。2003年,英国药物安全委员会发布警告帕罗西汀有导致自杀这一副作用的危险,随后将警告扩展至所有新型抗抑郁药2。美国食品与药品管理局随即也开始对儿童发出警告,后来也将警告扩展至成人3。MOSTOFTHECASEREPORTSTHATWEREPUBLISHEDONTHESUBJECTDEALTWITHDEPRESSIVEPATIENTSSOMEOFTHESECASEREPORTSDESCRIBEDTREATMENTRESISTANTPATIENTSORPATIENTSWHOWERETREATEDWITHHIGHERTHANCOMMONPRACTICEDRUGDOSESALLTHESEDRAWBACKSLIMITEDTHEABILITYTOREACHCONCLUSIVEANSWERSREGARDINGTHETRUECONNECTIONBETWEENSUICIDEANDANTIDEPRESSANTTREATMENT4已发表的关于此问题的病例报告大多涉及抑郁患者。其中,部分病例报告描述的是对治疗耐受的患者或以高于常用药物剂量的剂量治疗的患者。所有这些缺点限制了就自杀于抗抑郁药治疗之间的真实联系得出最终结论4。THEFOLLOWINGDESCRIPTIONOFAPATIENTISUNIQUEBECAUSEHESUFFEREDFROMANXIETYDISORDERANDWASNEITHERDEPRESSEDNOREXPERIENCINGSUICIDEIDEATIONPRIORTOTHEBEGINNINGOFTHEANTIDEPRESSANTTREATMENTTHISCASEHIGHLIGHTSTHEIDIOSYNCRATICRESPONSEOFSUICIDALIDEATIONEMERGINGFROMTHETREATMENTWITHANTIDEPRESSANTS下文对患者的描述的独特之处在于,他患有焦虑症,开始抗抑郁治疗之前既没有抑郁,也没有出现过自杀意念。本病例突出了抗抑郁药治疗期间出现自杀意念的异质性反应。CASEPRESENTATION病例描述WEREPORTONA19YEAROLDMALEPATIENTWHOSUFFERSFROMPANICDISORDERACCORDINGTOTHEDSMIVDIAGNOSTICANDSTATISTICALMANUALOFMENTALDISORDERS,VERSIONIV5CRITERIASINCETHEAGEOF15HEWASALSODIAGNOSEDWITHCOMORBIDNARCISSISTICPERSONALITYDISORDER,BUTWITHOUTANYDRUGORALCOHOLABUSEINTHEPASTNOMEDICALOROTHERHEALTHPROBLEMSWEREKNOWNORPRESENTONSETOFPANICATTACKSWASATAGE15WHENHISPARENTSDIVORCEDINITIALPHARMACOLOGICALTREATMENTWITHFLUOXETINE20MGTITEREDUPWITHINAFEWWEEKSWASCOMBINEDWITHINDIVIDUALANDFAMILYPSYCHOTHERAPYONANOUTPATIENTLEVELDUETOLACKOFRESPONSETHEPATIENTWASSWITCHTOFLUVOXAMINE150MGAFTER2MONTHSDESPITETHISINTENSIFIEDTREATMENTREGIMEN,PANICATTACKSCONTINUEDANDHISOVERALLSTATEDETERIORATEDEVENTUALLYLEADINGTOHOSPITALIZATIONTOAYOUTHINPATIENTWARDTREATMENTWASCHANGEDTOVENLAFAXINEINITIALLYWITH75MG/DAYINTHEMORNINGALMOSTIMMEDIATELYTHEPATIENTEXPERIENCEDFREQUENTSUICIDETHOUGHTSALONGWITHFEELINGSOFDESPAIRANDHOPELESSNESSTHETHOUGHTSFRIGHTENEDHIMTOTHEPOINTOFSUFFERINGFREQUENTPANICATTACKSTHISDETERIORATIONWASINTERPRETEDASASIGNOFTREATMENTRESISTANCEANDTHEREFORE,VENLAFAXINEWASTITEREDUPTO300MG/DAYSUBSEQUENTLY,THEPATIENTMADEHISFIRSTSUICIDEATTEMPTBYDRINKINGACIDTHATWASLEFTBYACARELESSHOSPITALWORKERNOPSYCHOSOCIALFACTORSORSTRESSFULLIFEEVENTSWEREDETECTEDTOHAVECONTRIBUTEDTOTHESUICIDEATTEMPT我们在此报告的是一名患有惊恐障碍的19岁男性,他是在15岁时根据DSMIV(精神疾病诊断与统计手册,第4版)5标准被确诊的。他还被诊断出同时患有自恋型人格障碍,但既往没有用过任何药物,无酒精滥用史。未知或未见医学或其他健康问题。患者15岁时父母离异,当年首次出现了惊恐发作。最初在门诊用氟西汀20MG(数周内逐渐滴定增大剂量)联合个人和家庭心理治疗。由于患者对治疗反应不佳,2个月后将药物换为氟伏沙明150MG。虽然更换为此强化治疗方案,患者仍发生惊恐发作,整体状态逐渐恶化,最终入住青年病房住院治疗。治疗方案改为初始早上服用文拉法辛75MG/天。服药后患者随即频繁出现自杀念头,伴有绝望和无助感。自杀念头使他受到了惊吓,惊恐发作频繁发生。这种病情恶化被解释为治疗耐受的表现,因此,文拉法辛滴定增大剂量300MG/天。后来,患者喝了医院工人疏忽留下的酸,首次企图自杀。未发现导致此次自杀企图的心理社会因素或应激生活事件。FOLLOWINGTHISEVENT,PAROXETINEWASTRIALEDUPTO20MG/DLEADINGTOALMOSTFULLREMISSIONANDONLYRAREPANICATTACKSDURINGTHEFOLLOWING4WEEKSATTHATPOINTINTIME,WHENTHEPATIENTWASDISCHARGEDHOME,HISGENERALFUNCTIONINGWASNORMALINTHENEXT4YEARSTHEPATIENTCONTINUEDONPAROXETINE20MG/DBECAUSEWHENHETRIEDLOWERINGTHISDOSEACCORDINGTOHISPSYCHIATRIST,HEFELTMOREANXIOUSHEWASREGULARLYFOLLOWEDUPDURINGTHISTIMEANDEXPERIENCEDRARECLASSICPANICATTACKSMOSTLYDURINGSTRESSFULTIMES患者自杀未遂后,试用帕罗西汀20MG/天,随后4周患者几乎完全缓解,惊恐发作很少出现。经过一段时间后患者出院回家,当时他的一般功能是正常的。随后4年,患者依照精神科医师的医嘱试图减少帕罗西汀的剂量时就会感到焦虑加重,因此他继续用20MG/天。这段时间内他定期随访,在应激期内基本上很少发生典型的惊恐发作。AFTER4YEARSOFCONTINUOUSANTIDEPRESSANTTREATMENTWITHPAROXETINE,THEPATIENTSTARTEDTOCOMPLAINABOUTDELAYEDEJACULATIONWHICHWASATTRIBUTEDTOPAROXETINEASACONSEQUENCEOTHERANTIDEPRESSANTSWERETRIALED,NONEOFWHICHIMPROVEDHISSEXUALDISTURBANCEORCAUSEDANYWORSENINGOFHISANXIETYFINALLYWHENVENLAFAXINEWASTRIALEDAGAINDUETOLACKOFEFFECTIVEALTERNATIVESWITHNO/LITTLESIDEEFFECTS,THEPATIENTCOMPLAINEDABOUTFREQUENTSUICIDETHOUGHTSAFTERONEWEEKOFVENLAFAXINEXR75MGOTHERMEDICATIONWASNOTUSEDATTHATTIMEHEAPPEAREDINTHEOUTPATIENTCLINICASVERYANXIOUS,REPORTEDBEINGAFRAIDTOSTAYONHISOWN,WASTERRIFIEDTHATHEMIGHTLOSECONTROLANDTOUNINTENTIONALLYHARMHIMSELFTHESUICIDALTHOUGHTSWEREEXPERIENCEDINTHESAMEWAYASTHESUICIDALIDEATIONANDSUICIDEATTEMPTFROMHISADOLESCENTYEARSAFTERSWITCHINGTODULOXETINE60MG/DAY,THESUICIDALTHOUGHTSCOMPLETELYDISAPPEARED持续用帕罗西汀抗抑郁治疗4年后,患者开始述有射精延迟,这是由帕罗西汀导致的。因此,试用了其他抗抑郁药,这些药物均无法改善他的性功能障碍,但也没有导致焦虑加重。最后,由于没有无/很少副作用的有效替代药物,只能再次使用文拉法辛。用了文拉法辛XR75MG一周后,患者主诉经常出现自杀念头。当时没有用其他药物。他来门诊就诊时显得非常焦虑,据说不敢独处,害怕可能会失控并无意中伤害自己。此次的自杀念头出现的方式与青春期的自杀意念和自杀企图是一样的。将药物更换为度洛西汀60MG/天后,自杀念头完全消失。DISCUSSION讨论INTHELASTYEARS,SEVERALLARGERETROSPECTIVEANALYSESWERECARRIEDOUTINORDERTOEXPANDTHEUNDERSTANDINGOFTHEPHENOMENONOFSUICIDALIDEATIONDUETOSSRIMEDICATIONTHESESTUDIESPOINTEDOUTTHATREGARDINGTHERISKOFDEVELOPINGSUICIDEACTS,THENEWANTIDEPRESSANTSPRESENTWITHASIMILARRISKOFSUICIDALIDEATIONASTHEOLDTCA,6,7ITWASALSOCONCLUDEDTHATANTIDEPRESSANTSASAGROUPELEVATETHERISKFORSUICIDECOMPAREDTOPLACEBO8过去几年中进行了几项大型回顾性分析,以加深对SSRI药物导致的自杀意念这一现象的了解。这些研究指出,对于发生自杀行为的风险,新型抗抑郁药导致的自杀意念风险与旧的三环类抗抑郁药(TCA)相当6,7。研究得出如下结论与安慰剂相比,所有抗抑郁药均会使自杀风险升高8。ONTHEOTHERHAND,MANYSTUDIESCONFIRMTHERECIPROCALCONNECTIONBETWEENTHEINCREASEDUSEOFANTIDEPRESSANTSANDTHEDECLINEOFSUICIDEFOREXAMPLE,INASTUDYCONDUCTEDINSCANDINAVIA,VICTIMSOFSUICIDEWERECOMPAREDTOPEOPLEWHODIEDASARESULTOFNATURALORTRAUMATICEVENTSTHESUICIDEGROUPWASRELATIVELYUNDERTREATEDWITHANTIDEPRESSANTS9AMORERECENTREPORTAPPLYINGAGGREGATEDDATASUGGESTSTHATTHEINCREASEDUSEOFSSRISISRELATEDTODECREASEDSUICIDERATESWHEREASTCAPRESCRIPTIONSWERERELATEDTOINCREASEDSUICIDERATES10ONASIMILARPOINT,ARETROSPECTIVEANALYSESOFTHERELATIONSHIPBETWEENPRESCRIPTIONSOFSSRISANDSUICIDERATESSUGGESTSTHATTHEDECREASEOFSSRIPRESCRIPTIONSFORCHILDRENANDADOLESCENTS,BOTHINTHEUNITEDSTATESANDTHENETHERLANDS,AFTERUSANDEUROPEANREGULATORYAGENCIESISSUEDWARNINGSABOUTAPOSSIBLESUICIDERISKWITHANTIDEPRESSANTUSEINPEDIATRICPATIENTS,WASASSOCIATEDWITHINCREASESINSUICIDERATESINCHILDRENANDADOLESCENTS11另一方面,许多研究证实了抗抑郁药使用增多与自杀减少呈反相关。例如,在北欧进行的一项研究将自杀死亡者与自然死亡者或创伤事件死亡者进行比较。自杀组用抗抑郁药治疗相对不充分9。最近一份汇集了大量数据的报告表明,SSRI使用增多与自杀率下降有关,而TCA处方增多与自杀率上升有关10。与此相似的是,一项回顾SSRI处方与自杀率的联系的分析表明,自从美国和欧盟监管机构发布了儿科患者使用抗抑郁药有可能会发生自杀的警告以来,美国和荷兰儿童与青少年的SSRI处方减少与他们的自杀率上升有关11。COMBININGTHISRESEARCHTHECONCLUSIONISTHATFORTHESOCIETYASAGROUP,THEUSEOFANTIDEPRESSANTSISBENEFICIALNEVERTHELESS,FORCERTAININDIVIDUALS,THESEMEDICINESCOULDCAUSESUICIDEIDEATIONANDPUTTHEMINGREATRISK12THEREFORE,IDENTIFYINGTHESEPATIENTSISIMPORTANTFROMACLINICALANDLEGALPERSPECTIVE综上,该研究的结论是对于整个患者群体而言,使用抗抑郁药是有好处的。但是,对于某些个体,这些药物会导致自杀意念,使他们面临极大的危险12。因此,从临床和法律的角度来说,鉴定这些患者极为重要。THERAISINGAWARENESSOFTHESUICIDALRISKFORDEVELOPINGSUICIDALIDEATIONANDBEHAVIORDURINGTREATMENTWITHANTIDEPRESSANTSCAUSESADRAMATICCHANGEOFTHEATTITUDETOWARDTHESEDRUGSTHEPRESENTEDCASEDEMONSTRATESFORTHEFIRSTTIMEARECURRENCEOFSUICIDALITYFOLLOWINGANTIDEPRESSANTSINPATIENTSWITHANXIETYDISORDERTHEREFORE,SUICIDALITYASADIRECTCONSEQUENCEOFANTIDEPRESSANTTREATMENTISNOTRESTRICTEDTOPATIENTSWITHMAJORDEPRESSIVEDISORDERIMPROVEDUNDERSTANDINGOFTHERISKSANDDETECTIONOFEARLYCLINICALWARNINGSIGNSWHILEUSINGANTIDEPRESSANTSISTHEREFOREVITALFORTHESEPATIENTS患者逐渐意识到用抗抑郁药治疗期间有出现自杀意念和行为的风险,因此他们对这些药物的态度发生了很大变化。本病例首次描述了焦虑症患者用抗抑郁药治疗后再次出现自杀意念。因此,自杀作为抗抑郁治疗的直接后果,并非只局限发生于重度抑郁症患者。因此,加深对使用抗抑郁药的风险的了解和发现自杀的早期临床先兆对这些患者很重要。THEUNDERSTANDINGOFTHEPRECISEMECHANISMSBYWHICHANTIDEPRESSANTSMAYCAUSESUICIDALITYISSTILLLACKINGFEWTHEORIESWEREPUTFORWARDALONGTHEYEARSTHATCANBEDIVIDEDINTOTWOGROUPSEITHERATTRIBUTEDTODEPRESSIVESYMPTOMSORATTRIBUTEDTOTHEDRUGITSELFTHEORIESABOUTATTRIBUTIONTODEPRESSIVESYMPTOMSCLAIMEDTHATTHISPHENOMENONISMERELYACONSEQUENCEOFACLINICALWORSENINGOFTHESPECIFICDISORDERWHICHISKNOWNASTHEPARADOXICALSUICIDE12,13OTHERSSPECULATEDTHATTHESEPATIENTSMAYSUFFERFROMANUNDIAGNOSEDBIPOLARDISORDER14THEORIESTHATFOCUSONSIDEEFFECTOFTHEDRUGCLAIMEDTHATTHEDEVELOPMENTOFAKATHISIADUETOANTIDEPRESSANTTREATMENTPOSSIBLYISTHECAUSEFORSUICIDALITY15BEYONDTHESEEXPLANATIONS,OURCASECONTRIBUTESTOOTHERTHEORIESASFOLLOWSIDIOSYNCRATICRESPONSETOPSYCHOTROPICAGENTSMIGHTHAVEOCCURREDINBOTHSUSCEPTIBLEINDIVIDUALSASSUICIDALITYSUBSIDEDWHENSWITCHINGTOANOTHERDRUGOFTHESAMECLASSTHISTHEORYGAINSMORESTRENGTHWHENCONSIDERINGTHATEVENTREATMENTOFNORMALSUBJECTSCOULDRESULTINSUICIDEIDEATION4FURTHERMORE,ASUDDENONSETOFSUICIDALFEELINGSISAWELLKNOWNBUTSTILLRELATIVELYUNDERESTIMATEDANDNOTWIDELYUNDERSTOODPHENOMENONPATIENTSOFTENDESCRIBEFEELINGSOFHOPELESSNESSANDDESPAIRTHATMAYDEVELOPAFTERSTARTINGTREATMENTWITHANANTIDEPRESSANT12THATMAYLEADTOSUICIDALITYT

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