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Written by Professor SW Tang 作者 : 邓兆华教授 Presented by Dr. David Wong 讲者 : 王大卫 医生

Use of Psychiatric Drugs in Children: Risks & Benefits 儿童 们使用精神科药物的风险与效益. Written by Professor SW Tang 作者 : 邓兆华教授 Presented by Dr. David Wong 讲者 : 王大卫 医生. Potential Conflict of Interests.

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Written by Professor SW Tang 作者 : 邓兆华教授 Presented by Dr. David Wong 讲者 : 王大卫 医生

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  1. Use of Psychiatric Drugs in Children: Risks & Benefits儿童们使用精神科药物的风险与效益 Written by Professor SW Tang 作者: 邓兆华教授 Presented by Dr. David Wong 讲者: 王大卫医生

  2. Potential Conflict of Interests Professor Tang received sponsorships and supports from E Lilly, GSK, Lundbeck, Astra Seneca, Wyeth, Janssen,Organon. Professor Tang does not own shares/stocks in above companies. Professor Tang is a faculty member of Lundbeck Institute.

  3. Use of Psychiatric Drugs in Children: Risks & Benefits儿童们使用精神科药物的风险与效益 Many more young patients are on psychiatric drugs越来越多青少年病人服用精神科药物

  4. Age 1-17 Surge in the use of Antipsychotics in Child and Adolescence

  5. Possible effects of Psychiatric Drugs in Children & Adolescence儿童期和靑春期使用精神科药物治疗可能的影响 • Pre-natal产前: • Before conception 受精前(effects on germ cells)(对生殖细胞的影响). • At conception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) • 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) • Around Puberty (hormones)青春期(荷尔蒙) • Young Adulthood (brain consolidation)成人期

  6. Possible effects of Psychiatric Drugs in Children & Adolescence儿童期和靑春期使用精神科药物治疗可能的影响 • Lipophilic: brain is a fatty organ, many psychiatric drugs are highly fat soluble and drugs will stay for long time. 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: not only going to sites you wanted, but to many other unwanted targets. 多目标: 不仅影响單一的目标, 而且可能影响其他系统.

  7. Possible effects of Psychiatric Drugs in Children & Adolescence儿童期和靑春期使用精神科药物治疗可能的影响 3. Teratogeniety畸形形成 (e.g. >25 mg paroxetine daily):not easy to control. 例如每日服用超过 25毫克帕罗西汀可引至畸形形成现象. • Non-teratogeneity effects: other biological results (e.g. infant persistent pulmonary hypertension: 6-12 /1000 babies on paroxetine). 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).

  8. Possible effects of Psychiatric Drugs in Children & Adolescence儿童期和靑春期使用精神科药物治疗可能的影响 5. Drug-drug interaction: patient may be taking multiple drugs causing CYP enzymes interaction. Many psychiatric drugs are potent CYP enzyme inhibitors. 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. Withdrawal effects(~30% newborn exposed to Paroxetine last trimester): discontinuation causes rebound 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.

  9. Possible effects of Psychiatric Drugs in Children & Adolescence儿童期和靑春期使用精神科药物治疗可能的影响 7. Developmental effects: body is continuing developing , e.g. lithium effects on thyroid. 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. Hormonal effects: multiple and seldom noticed 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.

  10. Suicidality in Young vs Old caused by Paroxetine由服用帕罗西汀所造成的青少年與老年自杀的比較 • Suicidality associated with use of Paroxetine compared to placebo treated depressives: 帕罗西汀相比安慰剂与自杀倾向的关联： • Increased:增加: Age: < 18 (14 more cases); 18- 24 (5 more cases) 年龄: <18（多14宗） 18-24（多5宗） • Decreased :减少: Age: 25-64 (fewer by 1 case); >65 (fewer by 6 cases) 年龄: 25-64(少1宗); > 65 (小6宗)

  11. Suicidality in Young vs Old caused by Paroxetine由服用帕罗西汀所造成的青少年與老年自杀的比較 However, we begin to seesome disagreement 但是我们开始看见不同的论证

  12. Drop Drop in SSRI prescription rates in younger ages in US Gibbons et al,: Am J Psychiatry. 2007 Sep;164(9):1356-63.

  13. Rise in suicides Age 5-19 in US Gibbons et al. : Am J Psychiatry. 2007 Sep;164(9):1356-63.

  14. SSRI & Child /Adolescent SuicideSSRI與兒童/青少年自殺 “After adjustment for sex, race, income, access to mental health care, and county-to-county variability in suicide rates, higher SSRI prescription rates were associated with lower suicide rates in children and adolescents” 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 Gibbons et al.: Am J Psychiatry. 2006 Nov;163(11):1898-904.

  15. Alternate Pathways对身体另类的影响 • Metabolic 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: • thyroid (lithium) 甲状腺(锂盐) • Type II diabetes(olanzapine) 糖尿病II 形 • memory loss (SSRIs)记忆力变差的现象(抗抑郁药)

  16. Trophic and hormonal effects 代谢和荷尔蒙的影响 • Psychiatric drugs may cause hormone changes: e.g. 精神科药物能可能对内分泌系统的影响,如 • Prolactin (neuroleptics) 促乳激素(抗精神分裂病药物),, • metabolic syndromes (some atypical antipsychotics) the long term effect of which remain unkown 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 • Neurogenesis effects: atypical antipsychotics and antidepressant drugs are found to induce hippocampal / subventricular neurogenesis and neuroproliferation in stressed animal models 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

  17. Anti-stress抗压力 • Effects of antidepressant drugs on 抗抑郁药物有以下效果: • Dendritic spines ( increased)树突状刺 (增加) • Dendrites (prolonged)树突 (延长) • Neurons (anti-atropic)神经元(抗萎缩) • Are opposite to that of stress associated with cortisol elevation 压力引至体内皮质醇上升, 抗抑郁药物侧有相反的效果.

  18. Lessons from animal experiments 动物实验的教训 • Although structural/ metabolic differences are possible between human and rats, 虽然人和鼠的结构/新陈代谢有一定的区别 • Many drug induced phenomena are reproducible in human neurons / 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.

  19. Treatment Vs Non-treatment 治疗/不治疗 • Balancing treatment and non-treatment: pros and cons (price [how much] for benefits [how much]) 平衡治疗和不治疗的利與弊(代价[多少?]效益[多少? ] ) • Balancing acute (treatment) vs chronic effects (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 and tertiary) consequences of psychiatric illnesses due to delayed or non-treatment may be disastrous. 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

  20. Early Treatment to avoid secondary and Tertiary non-treatment consequences及早治疗可避免第二波和三波的效应 • Con: Early treatment反对及早治疗: Psychotropic drugs may be associated with 使用药物可能 • biological damage (e.g. possible early neuronal migration interference) 引起破坏(例如可能干扰早期神经细胞迁移) • Suicidality with SSRIs for age <18 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

  21. Early Treatment to avoid secondary and Tertiary non-treatment consequences及早治疗可避免二波和三波的效应 • Pro: Early treatment avoids pre-natal or early brain developmental effects as a result of psychiatric disorder及时的早期治疗可以减少抑郁(或其他精神病)母亲对胎兒/婴儿直接/间接的影响 • Causing secondary and tertiary consequences, e.g. developmental deficits, school failure 第二波和三波的严重效应，例如:成长门题、学业问题

  22. Examples实例 • ADHD: developmental concerns versus school performance and classroom behavior 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 depression itself 重性抑郁症: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 effects (infant persistent pulmonary hypertension, teratogeniety, 5HT withdrawal, 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)

  23. Final Decision最后决定 Price(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.

  24. End Thank you, For details, please e-mail Prof. Tang S W. 多谢 如有回应及意见,请电邮给邓兆华教授mswtang@hkucc.hku.hk

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