Written by Professor SW Tang Presented by Dr. David Wong 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 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.

Many more young patients are on psychiatric drugs 越来越多青少年病人服用精神科药物 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

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

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

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.

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).

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.

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.

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)

However, we begin to see some disagreement 但是我们开始看见不同的论证 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 see some disagreement 但是我们开始看见不同的论证

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

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

SSRI & Child /Adolescent Suicide SSRI 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.

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)        

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

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.

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.

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

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

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

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)

Price(代价) ~ Benefits (效益) 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.

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