1. 門 診疑義 處 方 討 論 Use of Methylphenidate in Traumatic Brain Injury (TBI) 報告日期： 99.3.30 黃信裕 藥師

3. Content 1. Methylphenidate 之藥理作用 2. Methylphenidate 核准之適應症 3. Methylphenidate in TBI 之合理性 4. Methylphenidate in TBI 之建議劑量 5. Methylphenidate in TBI 之證據等級 6. Conclusion 7. References

4. Methylphenidate 之藥理作用

5. Mechanism of Action CNS stimulant Reuptake of Dopamine inhibitor Challman TD, Lipsky JJ. Methylphenidate: Its Pharmacology and Uses Mayo Clin Proc. 2000 Jul;75(7):711-21. Review

7. Methylphenidate 核准之適應症

8. 衛生署核准適應症

9. FDA 核准適應症

10. Methylphenidate in TBI 之合理性

11. What are the most common problems after a TBI?

12. Thinking Changes (1)  Attention  Reduced concentration  Reduced visual attention  Inability to divide attention between competing tasks  Processing speed  Slow thinking  Slow reading  Slow verbal and written responses

13. Thinking Changes (2)  Communication  Difficulty finding the right words, naming objects  Disorganized in communication  Learning and Memory  Information before TBI intact  Reduced ability to remember new information  Problems with learning new skills

14. Methylphenidate in TBI 之證據等級

15. FDA Approval: Adult, no; Pediatric, no Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors efficacy Recommendation: Adult, Class IIb; Pediatric, Class IIb Strength of Evidence: Adult, Category B; Pediatric, Category B MICROMEDEX(r) Healthcare Series 醫療照護系列資料庫 (Database) Thomson MICROMEDEX Evidence (I)

16. ArticleELSignificant improvementNo Significant improvement Whyte et al., 1997 ISpeed of information processing Attentiveness during work task Caregiver ratings of attention Sustained attention Divided attention Distractibility Whyte et al.,2004 ISpeed of mental processingDistractibility, Vigilance/sustained attention Mooney and Haas, 1993 IAttention Kim et al., 2006 IIReaction time and accuracy of Visuospatial attention Lee et al., 2005IIRecognition reaction time and daytime alertness (when compared to sertraline) Recognition reaction time (when compared to placebo) Plenger et al., 1996 IIAttention span, divided attention and vigilance (at one month) Attention span, divided attention and vigilance (at three months) Kaelin et al., 1996 IIAttention span, sustained attention, divided attention Speech et al., 1993 IISustained attention Vigilance, Processing speed Gualtieri and Evans, 1988 II 10 subjects – sustained attention, divided attention, selective attention 5 subjects – no change Grade et al., 1988 IICognitive function Evidence (II) Sivan M et al. Clin Rehabil. 2010 Feb;24(2):110-21

17. Methylphenidate in TBI 之建議劑量

18. 1. Enhance attentional function Dose: 0.25–0.30 mg/kg bid 2. Enhance the speed of cognitive processing Dose: 0.25–0.30 mg/kg bid 3. Enhance learning and memory Dose: 0.30 mg/kg bid 4. Improve speed in mental processing Dose: 0.30 mg/kg bid Recommended Dose Neurobehavioral Guidelines Working Group, Warden DL, Gordon B, McAllister TW, Silver JM, Barth JT, Bruns J, Drake A, Gentry T, Jagoda A, Katz DI, Kraus J, Labbate LA, Ryan LM, Sparling MB, Walters B, Whyte J, Zapata A, Zitnay G. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006 Oct;23(10):1468-501

19. 醫師開立處方： Methylphenidate 10mg/tab, 1tab, QD ? 結果：可能造成改善症狀之劑量不足

20. 結論 Methylphenidate 用於 TBI( 創傷性腦損害 ) 乃屬於合理之治療，因為 TBI 會造成腦部神經性病變， 如：認知不足、注意力缺乏、記憶力減退 … 等 。 但是衛生署核准之適應症為過動兒症候群及 發作型嗜睡症，若醫師將 Methylphenidate 用於 器質性腦徵候群或腦震盪後徵候群，需考慮以自費 方式給予。

21. 參考資料 1.Siddall OM. Use of methylphenidate in traumatic brain injury. Ann Pharmacother. 2005 Jul-Aug;39(7-8):1309-13. Epub 2005 May 24. Review. 2. Sivan M, Neumann V, Kent R, Stroud A, Bhakta BB Pharmacotherapy for treatment of attention deficits after non-progressive acquired brain injury. A systematic review. Clin Rehabil. 2010 Feb;24(2):110-21. 3. Challman TD, Lipsky JJ. Methylphenidate: its pharmacology and uses. Mayo Clin Proc. 2000 Jul;75(7):711-21. Review.. 4. Neurobehavioral Guidelines Working Group, Warden DL, Gordon B, McAllister TW, Silver JM, Barth JT, Bruns J, Drake A, Gentry T, Jagoda A, Katz DI, Kraus J, Labbate LA, Ryan LM, Sparling MB, Walters B, Whyte J, Zapata A, Zitnay G. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006 Oct;23(10):1468-501. 5. MICROMEDEX(r) Healthcare Series 醫療照護系列資料庫 (Database) Thomson MICROMEDEX

22. Thank you for your attention

23. Background Deficits in attention are commonly seen in non-progressive acquired brain injury. The prevalence of attention deficits even after mild traumatic brain injury has been reported to range from 40-60% at 1-3 months post injury Pierce SR. et al. Arch Phys Med Rehabil 2002

24. Attention Focused Sustained Divided Alternating Selective