儿童们使用精神科药物的风险与效益

1UseofPsychiatricDrugsinChildren:Risks&Benefits儿童们使用精神科药物的风险与效益2PotentialConflictofInterestsProfessorTangreceivedsponsorshipsandsupportsfromELilly,GSK,Lundbeck,AstraSeneca,Wyeth,Janssen,Organon.ProfessorTangdoesnotownshares/stocksinabovecompanies.ProfessorTangisafacultymemberofLundbeckInstitute.3UseofPsychiatricDrugsinChildren:Risks&Benefits儿童们使用精神科药物的风险与效益Manymoreyoungpatientsareonpsychiatricdrugs越来越多青少年病人服用精神科药物SurgeintheuseofAntipsychoticsinChildandAdolescenceAge1-175A.Pre-natal产前:1.Beforeconception受精前(effectsongermcells)(对生殖细胞的影响).2.Atconception受精B.Atbirth(withdrawale.g.alcohol,heroin,paroxetine)出生时(脱瘾症状例如:酒精,海落英,帕罗西汀)C.BeforePuberty(developmentofneurons,prunning,erroneouscellmigrationinbrain)青春期前(神经发展及修展,错配的脑细胞迁移)D.AroundPuberty(hormones)青春期(荷尔蒙)E.YoungAdulthood(brainconsolidation)成人期PossibleeffectsofPsychiatricDrugsinChildren&Adolescence儿童期和靑春期使用精神科药物治疗可能的影响61.Lipophilic:brainisafattyorgan,manypsychiatricdrugsarehighlyfatsolubleanddrugswillstayforlongtime.脂溶性:脑是脂肪酸器官,许多精神病药物是高脂溶性,药物会留在体内一段长的时间.2.Multi-targets:notonlygoingtositesyouwanted,buttomanyotherunwantedtargets.多目标:不仅影响單一的目标,而且可能影响其他系统.PossibleeffectsofPsychiatricDrugsinChildren&Adolescence儿童期和靑春期使用精神科药物治疗可能的影响73.Teratogeniety畸形形成(e.g.25mgparoxetinedaily):noteasytocontrol.例如每日服用超过25毫克帕罗西汀可引至畸形形成现象.4.Non-teratogeneityeffects:otherbiologicalresults(e.g.infantpersistentpulmonaryhypertension:6-12/1000babiesonparoxetine).其他非畸形生理影响:(如每1000受母体内帕罗西汀影响的婴儿有6-12个持续性肺动脉高压案例).PossibleeffectsofPsychiatricDrugsinChildren&Adolescence儿童期和靑春期使用精神科药物治疗可能的影响85.Drug-druginteraction:patientmaybetakingmultipledrugscausingCYPenzymesinteraction.ManypsychiatricdrugsarepotentCYPenzymeinhibitors.药物相互作用:病者同时服同多种药物可能引至不稳定的药物浓度.许多精神病药物是p450酶抑制剂.6.Withdrawaleffects(~30%newbornexposedtoParoxetinelasttrimester):discontinuationcausesrebound脱瘾现象(〜30％受怀孕后期母体内帕罗西汀影响新生儿.)突然和母体分离时(分娩)会导至婴儿脱瘾现象.PossibleeffectsofPsychiatricDrugsinChildren&Adolescence儿童期和靑春期使用精神科药物治疗可能的影响97.Developmentaleffects:bodyiscontinuingdeveloping,e.g.lithiumeffectsonthyroid.人体是持续发展的，例如:由于锂盐的副作用,低甲状会影响生体发展.8.Hormonaleffects:multipleandseldomnoticed的:精神科藥物可能影响多種荷尔蒙系統.這方面甚少被关注.PossibleeffectsofPsychiatricDrugsinChildren&Adolescence儿童期和靑春期使用精神科药物治疗可能的影响10SuicidalityassociatedwithuseofParoxetinecomparedtoplacebotreateddepressives:帕罗西汀相比安慰剂与自杀倾向的关联：Increased:增加:Age:18(14morecases);18-24(5morecases)年龄:18（多14宗）18-24（多5宗）Decreased:减少:Age:25-64(fewerby1case);65(fewerby6cases)年龄:25-64(少1宗);65(小6宗)SuicidalityinYoungvsOldcausedbyParoxetine由服用帕罗西汀所造成的青少年與老年自杀的比較11However,webegintoseesomedisagreement但是我们开始看见不同的论证SuicidalityinYoungvsOldcausedbyParoxetine由服用帕罗西汀所造成的青少年與老年自杀的比較DropinSSRIprescriptionratesinyoungeragesinUSGibbonsetal,:AmJPsychiatry.2007Sep;164(9):1356-63.DropRiseinsuicidesAge5-19inUSGibbonsetal.:AmJPsychiatry.2007Sep;164(9):1356-63.“Afteradjustmentforsex,race,income,accesstomentalhealthcare,andcounty-to-countyvariabilityinsuiciderates,higherSSRIprescriptionrateswereassociatedwithlowersuicideratesinchildrenandadolescents”撇取不同因素对自杀率的影响后,(如性别,种族,收入及国家区分),SSRIs的使用率越高,青少年的自杀率反而下降Gibbonsetal.:AmJPsychiatry.2006Nov;163(11):1898-904.SSRI&Child/AdolescentSuicideSSRI與兒童/青少年自殺15Metaboliceffects/shiftingunderpsychiatricdrugsmayhavelongtermeffects:精神科药物可能有长期的代谢影响e.g.例如:1.thyroid(lithium)甲状腺(锂盐)2.TypeIIdiabetes(olanzapine)糖尿病II形3.memoryloss(SSRIs)记忆力变差的现象(抗抑郁药)AlternatePathways对身体另类的影响16Psychiatricdrugsmaycausehormonechanges:e.g.精神科药物能可能对内分泌系统的影响,如1.Prolactin(neuroleptics)促乳激素(抗精神分裂病药物),,2.metabolicsyndromes(someatypicalantipsychotics)thelongtermeffectofwhichremainunkown代谢症候群(非典型抗重性精神病药物)暂时未知长期服用精神药物對内分泌系统的影响Neurogenesiseffects:atypicalantipsychoticsandantidepressantdrugsarefoundtoinducehippocampal/subventricularneurogenesisandneuroproliferationinstressedanimalmodels但是在动物实验过程中,有证据显示非典型抗重性精神病药物和抗抑郁药物可影响海马/脑室的神经元增生及繁殖Trophicandhormonaleffects代谢和荷尔蒙的影响17Effectsofantidepressantdrugson抗抑郁药物有以下效果:Dendriticspines(increased)树突状刺(增加)Dendrites(prolonged)树突(延长)Neurons(anti-atropic)神经元(抗萎缩)Areoppositetothatofstressassociatedwithcortisolelevation压力引至体内皮质醇上升,抗抑郁药物侧有相反的效果.Anti-stress抗压力18Althoughstructural/metabolicdifferencesarepossiblebetweenhumanandrats,虽然人和鼠的结构/新陈代谢有一定的区别Manydruginducedphenomenaarereproducibleinhumanneurons/primates但药物在鼠中引起的众多现象,可以在人的神经元系統內產生.Lessonsfromanimalexperiments动物实验的教训19A.Balancingtreatmentandnon-treatment:prosandcons(price[howmuch]forbenefits[howmuch])平衡治疗和不治疗的利與弊(代价[多少?]效益[多少?])B.Balancingacute(treatment)vschroniceffects(non-treatment)平衡药物使用后遗症(急性)与不治疗帶來的后果(慢性)teratogenietyseemedlessofaconcern似乎畸形形成的现象并没有预期那么严重。2.chronic(secondaryandtertiary)consequencesofpsychiatricillnessesduetodelayedornon-treatmentmaybedisastrous.及早治疗可避免精神料疾病帶來的第二波和第三波严重效应TreatmentVsNon-treatment治疗/不治疗20Con:Earlytreatment反对及早治疗:Psychotropicdrugsmaybeassociatedwith使用药物可能biologicaldamage(e.g.possibleearlyneuronalmigrationinterference)引起破坏(例如可能干扰早期神经细胞迁移)SuicidalitywithSSRIsforage18對18歲以下的青少年,自杀傾向与5-羟色胺再摄取抑制剂(SSRIs)有未明的关联EarlyTreatmenttoavoidsecondaryandTertiarynon-treatmentconsequences及早治疗可避免第二波和三波的效应21Pro:Earlytreatmenta