氯胺酮與抑郁癥課件

氯胺酮與抑郁癥查找資料PPT制作姚磊查找資料PPT制作與優(yōu)化錢(qián)雅竹整理優(yōu)化PPT展示與回答黃玉敏分工介紹背景介紹新藥——氯胺酮

總結(jié)提綱123精力減退抑郁心境興趣喪失自我評(píng)價(jià)低抑郁癥睡眠障礙食欲下降自殺觀念精神運(yùn)動(dòng)遲滯抑郁癥背景介紹臨床癥狀腦中單胺遞質(zhì)去甲腎上腺素(NE)和5羥色胺(5-HT)功能不足環(huán)境及個(gè)體心理因素——行為認(rèn)知、精神衛(wèi)生等背景介紹發(fā)病機(jī)制單胺遞質(zhì)理論神經(jīng)遞質(zhì)理論單相性抑郁癥(即重性抑郁癥和精神抑郁癥)、適應(yīng)性障礙、輕微抑郁癥、季節(jié)情感性精神障礙(SAD)，經(jīng)前期焦慮癥(PMDD)、產(chǎn)后抑郁癥、非典型抑郁癥及雙相性精神障礙、躁郁癥等神經(jīng)回路學(xué)說(shuō)背景介紹現(xiàn)狀世界衛(wèi)生組織2005年統(tǒng)計(jì)，各種抑郁癥的患病率約占全球人口的11%。在中國(guó)，目前抑郁癥的患病率約為3%～5%，抑郁癥患者估計(jì)有3600萬(wàn)人。抑郁癥已成為世界第4大疾患,預(yù)計(jì)到2020年,可能成為僅次于冠心病的第二大疾病。與高發(fā)病率形成鮮明反差的是，目前全國(guó)地市級(jí)以上醫(yī)院對(duì)抑郁癥的識(shí)別率不到20%。而在現(xiàn)有抑郁癥患者中，只有不到10%的人接受了相關(guān)藥物治療。抑郁癥在我國(guó)造成的直接經(jīng)濟(jì)負(fù)擔(dān)約為141億元，間接經(jīng)濟(jì)損失約481億元，總經(jīng)濟(jì)負(fù)擔(dān)達(dá)到621億元。背景介紹現(xiàn)狀圖一：2007~2011年全球抗抑郁藥物市場(chǎng)規(guī)模心理學(xué)治療光療法睡眠剝奪法電休克治療音樂(lè)療法運(yùn)動(dòng)療法

藥物治療背景介紹治療方法三環(huán)類(lèi)抗抑郁藥（TCAs）第一代抗抑郁藥。TCAs阻斷突觸前膜對(duì)神經(jīng)遞質(zhì)5-HT、NE的再攝取——減少對(duì)5-HT、NE的攝取——提高在突觸間隙中的濃度——加強(qiáng)神經(jīng)傳導(dǎo)——抗抑郁非三環(huán)類(lèi)抗抑郁藥SSRIs、SNRIs、NDRIs、SARIs、NaSSAs等。新一代抗抑郁藥，曲唑酮、馬普替林、阿莫沙平、舍曲林、米氮平、帕羅西汀、氟西汀等單胺氧化酶抑制藥（MAOI）抑制MAO——5-HT、NE、DA等神經(jīng)遞質(zhì)氧化脫氨降解作用減少——單胺在組織中、神經(jīng)元突觸間隙中含量增多，濃度升高——治療抑郁癥其他神經(jīng)營(yíng)養(yǎng)因子類(lèi)抗抑郁藥植物類(lèi)抗抑郁藥P物質(zhì)拮抗藥抗抑郁藥背景介紹藥物治療——抗抑郁藥分類(lèi)新藥——氯胺酮發(fā)現(xiàn)過(guò)程Forexample,postmortemstudieshavereportedalteredNMDA-receptorcomplexesinthebraintissueofpatientswithDepressionHowtobegin?Converginglinesofevidencesuggesttheroleoftheglutamatergicsysteminthepathophysiologyandtreatmentofmooddisorders.ParticularlytheN-methyl-D-aspartate(NMDA)–receptorcomplex—mayplayanimportantroleinthepathophysiologyofDepressionAtthegeneticlevel,polymorphismsoftheGRIN1andGRIN2BgenescodingfortheNR1andNR2Bsubunits,respectively,havebeenassociatedwithDepression.Weknowthatketamine

isaNMDAantagonist!新藥——氯胺酮發(fā)現(xiàn)過(guò)程Forexample,postmortemstudieshavereportedalteredNMDA-receptorcomplexesinthebraintissueofpatientswithDepressionLet’sBeginCanketamineproducearapidantidepressanteffectsinsubjectswithmajordepression？

Design:Arandomized,placebo-controlled,double-blindStudyPatients:EighteensubjectswithDSM-IVmajor

depression(treatment-resistant)Age:18~65MainOutcomeMeasures:21-itemHamiltonDepressionRatingScale新藥——氯胺酮發(fā)現(xiàn)過(guò)程Subjectsreceivingketamineshowedsignificantimprovementindepressioncomparedwithsubjectsreceivingplacebowithin110minutesafterinjection,whichremainedsignificantthroughoutthefollowingweek.Theeffectsizeforthedrugdifferencewasverylargeafter24hours新藥——氯胺酮發(fā)現(xiàn)過(guò)程A,Proportionofresponders(50%improvementon21-itemHamiltonDepressionRatingScale28[HDRS])toketamineandplacebotreatmentfromminute40today7postinfusion(n=18).B,Proportionofremitters(HDRSscore7)toketamineandplacebotreatmentfromminute40today7postinfusion(n=18)新藥——氯胺酮發(fā)現(xiàn)過(guò)程Tomyknowledge,thisisthefirstreportofanymedicationorothertreatmentthatresultsinsuchapronounced,rapid,prolongedresponsewithasingledose.Thesewereverytreatment-resistantpatientsNIMHdirectorDr.ThomasInsel

Conclusion:RobustandrapidantidepressanteffectsresultedfromasingleintravenousdoseofanN-methyl-Daspartateantagonist;onsetoccurredwithin2hourspostinfusionandcontinuedtoremainsignificantfor1week.新藥——氯胺酮發(fā)現(xiàn)過(guò)程Changeindepressionscalescoresduring2weeksinpatientswithbipolardisordergivenplaceboandketamine(n=18).新藥——氯胺酮發(fā)現(xiàn)過(guò)程ProportionofrespondersandremittersafterketamineorplaceboinfusionbyMontgomery-AsbergDepressionRatingScale(MADRS)score.A,Proportionofresponders(50%improvementonMADRS)from40minutestoday14postinfusion(n=18).B,Proportionofremitters(MADRSscore10)from40minutestoday14postinfusion(n=18).新藥——氯胺酮發(fā)現(xiàn)過(guò)程Howketamineexertitsfunction？Ketaminecausesasignificantincrease(morethan60%)inglutamate(Glu)andgammaaminobutyricacid(GABA)levelsinthefrontofthebrain.

TheinvestigatorshypothesizethatthisincreaseinGluandGABAlevels,isresponsiblefortheantidepressantactionofthemedication.Butthemechanismremainunknown!新藥——氯胺酮發(fā)現(xiàn)過(guò)程Whatadverseeffectsketaminecause?Subjectswithmajordepression:perceptualdisturbances,confusion,elevationsinbloodpressure,euphoria,dizziness,andincreasedlibido.Themajorityoftheseadverseeffectsceasedwithin80minutesaftertheinfusion.Subjectswithbipolardepression:transitoryperceptualanddissociativedisturbances.Althoughmostketaminepatientsexperiencedsuchchanges,thosechangeswerenotassociatedwithantidepressantresponse;furthermore,somepatientswhorespondedtoketaminehadnosubstantialdissociativesymptoms.新藥——氯胺酮結(jié)論Butthereremainsomequestions:Canketamineproducerapidantidepressanteffectsinsubjectswithmajordepressionorbipolardepression?ClinicalTIdentifier:NCT00088699Phase1Themostsuitabledosageofketaminewhentreatingpatientswithmajordepression?ClinicalTIdentifier:NCT01558063Phase2參考資料ARandomizedTrialofanN-methyl-D-aspartateAntagonistinTreatment-ResistantMajorDepression2.ARandomizedAdd-onTrialofanN-meth