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

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

Methylphenidate 之藥理作用

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

Methylphenidate 核准之適應症

衛生署核准適應症

FDA核准適應症

Methylphenidate in TBI之合理性

What are the most common problems after a TBI?

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

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

Methylphenidate in TBI之證據等級

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)

Article EL Significant improvement No Significant improvement

Whyte et al., 1997

I Speed of information processing

Attentiveness during work task

Caregiver ratings of attention

Sustained attention

Divided attention

Distractibility

Whyte et al.,2004

I Speed of mental processing Distractibility,

Vigilance/sustained attention

Mooney and Haas, 1993

I Attention

Kim et al.,

2006

II Reaction time and accuracy of

Visuospatial attention

Lee et al., 2005 II Recognition reaction time and daytime alertness (when compared to sertraline)

Recognition reaction time

(when compared to placebo)

Plenger et al., 1996

II Attention span, divided attention and vigilance

(at one month)

Attention span, divided attention

and vigilance (at three months)

Kaelin et al., 1996

II Attention span, sustained attention, divided attention

Speech et al., 1993

II Sustained 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

II Cognitive function

Evidence (II)

Sivan M et al. Clin Rehabil. 2010 Feb;24(2):110-21

Methylphenidate in TBI 之建議劑量

1. Enhance attentional function Dose: 0.25–0.30 mg/kg bid2. Enhance the speed of cognitive processing Dose: 0.25–0.30 mg/kg bid3. Enhance learning and memory Dose: 0.30 mg/kg bid4. 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

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

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。

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

Thank you for your attention

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

Attention

Focused Sustained Divided Alternating Selective