Aripiprazole-induced Acute Dystonia in a Methylphenidate-medicated Boy Patient with Attention-deficit/Hyperactivity Disorder

Aripiprazole在常規使用methylphenidate之注意力不足過動症男童所引起的急性肌張力異常

10.29478/TJP.201009.0011

黃郁心(Yu-Hsin Huang)；李朝雄(Chau-Shoun Lee)

副作用 ； aripiprazole ； 急性肌張力異常 ； methylphenidate ； adverse effects ； aripiprazole ； dystonia ； methylphenidate

台灣精神醫學

24卷3期（2010 / 09 / 01）

236 - 239

英文

背景：Aripiprazole已被用在兒童青少年的精神疾患，但關於兒青病患因使用aripiprazole引起椎體外症候群的研究則較少，本文報告一位使用aripiprazole後產生急性肌張力異常的男童，並提出可能機轉。個案報告：一位因注意力不足過動症已常規使用精神興奮劑methylphenidate五個月的男童，因抽搐症狀使用每日2.5 mg之aripiprazole一週後，出現急性肌張力異常。以adverse drug reaction probability scale (Naranjo et al. 1981)評估aripiprazole是可能引起急性肌張力異常之因。結論：一可能機轉是青少年病人可能是CYP2D6與CYP3A4酶的代謝速度慢者。另一可能機轉：多巴胺接受器的敏感度會因多巴胺促進劑而改變，使用methylphenidate會使細胞間隙之多巴胺增加，使aripiprazole表現為多巴胺阻斷劑而產生急性肌張力異常。

Background: Aripiprazole has been increasingly used in children and adolescents with psychiatric disorders. Few investigations on aripiprazole-induced extra-pyramidal symptom have been performed in those young patients. We report a boy with aripirazole-induced acute dystonia. Case Report: A 10-year-old boy developed acute dystonia one week after the treatment with 2.5 mg aripiprazole per day for his tic-like symptom. He had taken methylphenidate five months before this adverse event for his attention-deficit/hyperactivity disorder. The adverse drug reaction probability scale was used and showed a probable relationship. Conclusion: We postulated two mechanisms. First, physiologic variations in pharmacokinetics among children, like the lower activities of cytochrome P450 (CYP) isoenzymes, CYP2D6 and CYP3A4, might enhance the risk. Second, the sensitivity of D2 receptors is vulnerable to change at the administration of dopaminergic agents. Methylphenidate would increase the synaptic level of dopamine, making aripiprazole like a D2 antagonist to induce acute dystonia thereafter.

1. Anderson, G.D.,Lynn, A.M.(2009).Optimizing pediatric dosing: a developmental pharmacologic approach.Pharmacotherapy,29,680-90.
2. Brandon, C.L.,Marinelli, M.,White, F.J.(2003).Adolescent exposure to methylphenidate alters the activity of rat midbrain dopamine neurons.Biol Psychiatry,54,1338-44.
3. Findling, R.L.,Kauffman, R.E.,Sallee, R.F.(2008).Tolerability and pharmacokinetics of aripiprazole in children and adolescents with psychiatric disorders: an open-label, dose-escalation study.J Clin Psychopharmacol,28,441-6.
4. Kwon, J.S.,Kim, E.,Kang, D.H.(2008).Taq1A polymorphism in the dopamine D2 receptor gene as a predictor of clinical response to aripiprazole.Eur Neuropsychopharmacol,12,897-907.
5. Lindsey, R.L.,Kaplan, D.,Koliatsos, V.,Walters, J.K.,Sandson, N.B.(2003).Aripiprazole and extrapyramidal symptoms.J Am Acad Child Adolesc Psychiatry,42,1268-9.
6. Murphy, T.K.,Bentson, M.A.,Soto, O.(2005).Case series on the use of aripiprazole for Tourette syndrome.Int J Neuropsychopharmacol,8,489-90.
7. Naranjo, C.A.,Busto, U.,Sellers, E.M.(1981).A method for estimating the probability of adverse drug reactions.Clin Pharmacol Ther,30,239-45.
8. Shen, Y.C.(2008).Amphetamine as a risk factor for aripiprazole-induced acute dystonia.Prog Neuropsychopharmacol Biol Psychiatry,32,1756-7.
9. Swainston Harrison, T.,Perry, C.M.(2004).Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder.Drugs,64,1715-36.
10. vanHarten, P.N.,Hoek, H.W.,Kahn, R.S.(1999).Acute dystonia induced by drug treatment.BMJ,319,623-6.