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1、1 Use of Psychiatric Drugs in Children:Risks&Benefits儿童儿童们使用精神科药物的风险与效益们使用精神科药物的风险与效益2PotentialConflictofInterestsProfessorTangreceivedsponsorshipsandsupportsfromELilly,GSK,Lundbeck,AstraSeneca,Wyeth,Janssen,Organon.ProfessorTangdoesnotownshares/stocksinabovecompanies.ProfessorTangisafacultymemberof
2、LundbeckInstitute.3 Use of Psychiatric Drugs in Children:Risks&Benefits儿童儿童们使用精神科药物的风险与效益们使用精神科药物的风险与效益Manymoreyoungpatientsareonpsychiatricdrugs越来越多青少年越来越多青少年病人病人服用精神科服用精神科药物药物Surge in the use of Antipsychotics in Child and Adolescence Age 1-175A.Pre-natal产前:1.Beforeconception受精前(effectsongermcells
3、)(对生殖细胞的影响).2.Atconception受精B.At birth(withdrawal e.g.alcohol,heroin,paroxetine)出生时(脱瘾症状 例如:酒精,海落英,帕罗西汀)C.Before Puberty(development of neurons,prunning,erroneous cell migration in brain)青春期前(神经发展及修展,错配的脑细胞迁移)D.Around Puberty(hormones)青春期(荷尔蒙)E.Young Adulthood(brain consolidation)成人期Possible effects
4、 of Psychiatric Drugs in Children&Adolescence儿童期儿童期和靑春期和靑春期使用精神科药物治疗可能的影响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
5、.多目标:不仅影响單一的目标,而且可能影响其他系统.Possible effects of Psychiatric Drugs in Children&Adolescence儿童期儿童期和靑春期和靑春期使用精神科药物治疗可能的影响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.infantpersistentpulmonaryhyp
6、ertension: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).Possible effects of Psychiatric Drugs in Children&Adolescence儿童期儿童期和靑春期和靑春期使用精神科药物治疗可能的影响使用精神科药物治疗可能的影响85.Drug-druginteraction:patientmaybetakingmultipledrugscausingCYPenzymesinteraction.Manypsychiatricdrugsarepot
7、entCYPenzymeinhibitors.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.Possible effects of Psychiatric Drugs in Children&Adolescence儿童期儿童期和靑春期和靑春期使用精神科药物治疗可能的影响使
8、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.Possible effects of Psychiatric Drugs in Children&Adolescence儿童期儿童期和靑春期和靑春期使用精神科药物治疗可能的影响使用精神科药物治疗可能的影响10S
9、uicidalityassociatedwithuseofParoxetinecomparedtoplacebotreateddepressives: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:65(fewerby6cases)年龄:25-64(少1宗);65(小6宗)Suicidality in Young vs Old caused by Paroxetine由服用由服用帕罗西汀所造成的青少年帕罗西汀所造成的青少年與老年與老年自杀自杀的比較的比較11However,webegintoseeso
10、medisagreement但是我们开始看见不同的论证Suicidality in Young vs Old caused by Paroxetine由服用由服用帕罗西汀所造成的青少年帕罗西汀所造成的青少年與老年與老年自杀自杀的比較的比較Drop in SSRI prescription rates in younger ages in US Gibbonsetal,:AmJPsychiatry.2007Sep;164(9):1356-63.DropRise in suicides Age 5-19 in US Gibbonsetal.:AmJPsychiatry.2007Sep;164(9)
11、: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):1
12、898-904.SSRI&Child/Adolescent SuicideSSRI 與兒童與兒童/青少年自殺青少年自殺 15Metabolic effects/shifting under psychiatric drugs may have long term effects: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)Alternate Pathways对身体另类对身体另类的影响的影响16Psychiatri
13、cdrugsmaycausehormonechanges: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:atypicalantipsychoticsandantidepressantdrugsarefoundtoinducehippo
14、campal/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 Trophic and hormonal effects 代谢代谢和荷尔蒙的影响和荷尔蒙的影响17Effectsofantidepressantdrugson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
15、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抗压力抗压力 18Althoughstructural/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.Lessons from
16、 animal experiments动物实验的教训动物实验的教训19A.Balancingtreatmentandnon-treatment:prosandcons(pricehowmuchforbenefitshowmuch)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)teratogeniety seemed less of a concern 似乎畸形形成的现象并没有预期那么严重。2.chronic(secondary
17、andtertiary)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Treatment Vs Non-treatment 治疗治疗/不治疗不治疗20Con: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
18、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Early Treatment to avoid secondary and Tertiary non-treatment consequences及及早治疗早治疗可可避免避免第第二二波波和三和三波波的效应的效应21Pro:Earlytreatmentavoidspre-natalorearlybraindevelopmentaleffectsasaresultofpsychiatricdisorder及时的早期治疗可以减少抑郁(或其他精神病)
19、母亲对胎兒/婴儿直接/间接的影响Causingsecondaryandtertiaryconsequences,e.g.developmentaldeficits,schoolfailure 第二波和三波的严重效应，例如:成长门题、学业问题Early Treatment to avoid secondary and Tertiary non-treatment consequences及及早治疗早治疗可可避免二避免二波波和三和三波波的效应的效应22ADHD:developmental concerns versus school performance and classroom ADHD:d
20、evelopmental concerns versus school performance and classroom behaviorbehavior 专注力不足及多动症:平衡药物引起的发育问题与学习专注的重要性MDD:suicidal increase from SSRI effect for age 18 versus true suicide from MDD:suicidal increase from SSRI effect for age 18 versus true suicide from depression itself depression itself 重性抑郁症
21、:平衡年青人服用5-羟色胺再摄取抑制剂(SSRIs)相对于抑郁症引發的自杀案例.SSRI during pregnancy:risks of post-partum depression&suicide versus fetal SSRI during pregnancy:risks of post-partum depression&suicide versus fetal effects(infant persistent pulmonary hypertension,teratogeniety,5HT withdrawal,effects(infant persistent pulmon
22、ary hypertension,teratogeniety,5HT withdrawal,5HT syndrome)5HT syndrome)怀孕期间服用SSRI:平衡产后的抑郁症及自杀风险相对于胎儿的影响（婴儿持续性肺动脉高压,畸形形成,脱癮症狀,五羟色胺综合病症)Examples实例实例23Price(代价)Benefits(效益)Discussion between patients,their relatives and family practitioners,pediatricians,psychiatrists and/or a obstetricians 病者和家属与医者(家庭医生,儿科,精神科,妇科等专科医生)共同了解及协商后的共识.Final Decision最后决定最后决定24EndThankyou,Fordetails,pleasee-mailProf.TangSW.多谢如有回应及意见,请电邮给邓兆华教授mswtanghkucc.hku.hk谢谢观看/欢迎下载BY FAITH I MEAN A VISION OF GOOD ONE CHERISHES AND THE ENTHUSIASM THAT PUSHES ONE TO SEEK ITS FULFILLMENT REGARDLESS OF OBSTACLES.BY FAITH I BY FAITH