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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

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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.

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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

Surge in the use of Antipsychotics in Child and Adolescence

Age 1-17

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A. Pre-natal 产前 : 1. Before conception 受精前 (effects on germ cells)( 对生殖细胞的影响 ).2. 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 )

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 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

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1. 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

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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 .

4. 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

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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

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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 .

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

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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 )

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

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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

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

Drop

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

“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.

SSRI & Child /Adolescent SuicideSSRI 與兒童 /青少年自殺

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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 : 1. thyroid (lithium) 甲状腺 ( 锂盐 ) 2. Type II diabetes(olanzapine) 糖尿病 II 形3. memory loss (SSRIs) 记忆力变差的现象 ( 抗抑郁药 )        

Alternate Pathways对身体另类的影响

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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1. Prolactin (neuroleptics) 促乳激素 ( 抗精神分裂病药物 ),, 2. 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

Trophic and hormonal effects 代谢和荷尔蒙的影响

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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 .

Anti-stress 抗压力

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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 .

Lessons from animal experiments动物实验的教训

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A. 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 ? ] )

B. 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

Treatment Vs Non-treatment 治疗 / 不治疗

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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及早治疗可避免第二波和三波的效应

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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

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

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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 )

Examples 实例

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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 .

Final Decision 最后决定

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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