氯胺酮与抑郁症课件

氯胺酮与抑郁症查找资料PPT制作姚磊查找资料PPT制作与优化钱雅竹整理优化PPT展示与回答黄玉敏分工介绍背景介绍新药——氯胺酮

总结提纲123精力减退抑郁心境兴趣丧失自我评价低抑郁症睡眠障碍食欲下降自杀观念精神运动迟滞抑郁症背景介绍临床症状脑中单胺递质去甲肾上腺素(NE)和5羟色胺(5-HT)功能不足环境及个体心理因素——行为认知、精神卫生等背景介绍发病机制单胺递质理论神经递质理论单相性抑郁症(即重性抑郁症和精神抑郁症)、适应性障碍、轻微抑郁症、季节情感性精神障碍(SAD)，经前期焦虑症(PMDD)、产后抑郁症、非典型抑郁症及双相性精神障碍、躁郁症等神经回路学说背景介绍现状世界卫生组织2005年统计，各种抑郁症的患病率约占全球人口的11%。在中国，目前抑郁症的患病率约为3%～5%，抑郁症患者估计有3600万人。抑郁症已成为世界第4大疾患,预计到2020年,可能成为仅次于冠心病的第二大疾病。与高发病率形成鲜明反差的是，目前全国地市级以上医院对抑郁症的识别率不到20%。而在现有抑郁症患者中，只有不到10%的人接受了相关药物治疗。抑郁症在我国造成的直接经济负担约为141亿元，间接经济损失约481亿元，总经济负担达到621亿元。背景介绍现状图一：2007~2011年全球抗抑郁药物市场规模心理学治疗光疗法睡眠剥夺法电休克治疗音乐疗法运动疗法

药物治疗背景介绍治疗方法三环类抗抑郁药（TCAs）第一代抗抑郁药。TCAs阻断突触前膜对神经递质5-HT、NE的再摄取——减少对5-HT、NE的摄取——提高在突触间隙中的浓度——加强神经传导——抗抑郁非三环类抗抑郁药SSRIs、SNRIs、NDRIs、SARIs、NaSSAs等。新一代抗抑郁药，曲唑酮、马普替林、阿莫沙平、舍曲林、米氮平、帕罗西汀、氟西汀等单胺氧化酶抑制药（MAOI）抑制MAO——5-HT、NE、DA等神经递质氧化脱氨降解作用减少——单胺在组织中、神经元突触间隙中含量增多，浓度升高——治疗抑郁症其他神经营养因子类抗抑郁药植物类抗抑郁药P物质拮抗药抗抑郁药背景介绍药物治疗——抗抑郁药分类新药——氯胺酮发现过程Forexample,postmortemstudieshavereportedalteredNMDA-receptorcomplexesinthebraintissueofpatientswithDepressionHowtobegin?Converginglinesofevidencesuggesttheroleoftheglutamatergicsysteminthepathophysiologyandtreatmentofmooddisorders.ParticularlytheN-methyl-D-aspartate(NMDA)–receptorcomplex—mayplayanimportantroleinthepathophysiologyofDepressionAtthegeneticlevel,polymorphismsoftheGRIN1andGRIN2BgenescodingfortheNR1andNR2Bsubunits,respectively,havebeenassociatedwithDepression.Weknowthatketamine

isaNMDAantagonist!新药——氯胺酮发现过程Forexample,postmortemstudieshavereportedalteredNMDA-receptorcomplexesinthebraintissueofpatientswithDepressionLet’sBeginCanketamineproducearapidantidepressanteffectsinsubjectswithmajordepression？

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

depression(treatment-resistant)Age:18~65MainOutcomeMeasures:21-itemHamiltonDepressionRatingScale新药——氯胺酮发现过程Subjectsreceivingketamineshowedsignificantimprovementindepressioncomparedwithsubjectsreceivingplacebowithin110minutesafterinjection,whichremainedsignificantthroughoutthefollowingweek.Theeffectsizeforthedrugdifferencewasverylargeafter24hours新药——氯胺酮发现过程A,Proportionofresponders(50%improvementon21-itemHamiltonDepressionRatingScale28[HDRS])toketamineandplacebotreatmentfromminute40today7postinfusion(n=18).B,Proportionofremitters(HDRSscore7)toketamineandplacebotreatmentfromminute40today7postinfusion(n=18)新药——氯胺酮发现过程Tomyknowledge,thisisthefirstreportofanymedicationorothertreatmentthatresultsinsuchapronounced,rapid,prolongedresponsewithasingledose.Thesewereverytreatment-resistantpatientsNIMHdirectorDr.ThomasInsel

Conclusion:RobustandrapidantidepressanteffectsresultedfromasingleintravenousdoseofanN-methyl-Daspartateantagonist;onsetoccurredwithin2hourspostinfusionandcontinuedtoremainsignificantfor1week.新药——氯胺酮发现过程Changeindepressionscalescoresduring2weeksinpatientswithbipolardisordergivenplaceboandketamine(n=18).新药——氯胺酮发现过程ProportionofrespondersandremittersafterketamineorplaceboinfusionbyMontgomery-AsbergDepressionRatingScale(MADRS)score.A,Proportionofresponders(50%improvementonMADRS)from40minutestoday14postinfusion(n=18).B,Proportionofremitters(MADRSscore10)from40minutestoday14postinfusion(n=18).新药——氯胺酮发现过程Howketamineexertitsfunction？Ketaminecausesasignificantincrease(morethan60%)inglutamate(Glu)andgammaaminobutyricacid(GABA)levelsinthefrontofthebrain.

TheinvestigatorshypothesizethatthisincreaseinGluandGABAlevels,isresponsiblefortheantidepressantactionofthemedication.Butthemechanismremainunknown!新药——氯胺酮发现过程Whatadverseeffectsketaminecause?Subjectswithmajordepression:perceptualdisturbances,confusion,elevationsinbloodpressure,euphoria,dizziness,andincreasedlibido.Themajorityoftheseadverseeffectsceasedwithin80minutesaftertheinfusion.Subjectswithbipolardepression:transitoryperceptualanddissociativedisturbances.Althoughmostketaminepatientsexperiencedsuchchanges,thosechangeswerenotassociatedwithantidepressantresponse;furthermore,somepatientswhorespondedtoketaminehadnosubstantialdissociativesymptoms.新药——氯胺酮结论Butthereremainsomequestions:Canketamineproducerapidantidepressanteffectsinsubjectswithmajordepressionorbipolardepression?ClinicalTIdentifier:NCT00088699Phase1Themostsuitabledosageofketaminewhentreatingpatientswithmajordepression?ClinicalTIdentifier:NCT01558063Phase2参考资料ARandomizedTrialofanN-methyl-D-aspartateAntagonistinTreatment-ResistantMajorDepression2.ARandomizedAdd-onTrialofanN-meth