주의력 및 정보처리속도 회복을 위한 약물치료

표 3-29. 주의력 및 정보처리속도 회복을 위한 약물치료

Medication	Dosing	Recommendation	Common side effects	Reference
First line: CNS stimulant (methylphenidate)
Methylphenidate	Start: 0.1mg/kg bid Max: 0.3mg/kg bid (아침 & 점심)	주의력과 정보처리속도 회복을 위해 투여가 권고됨 (INCOG-A)	Anorexia, nausea, vomiting, insomnia	INESSS-ONF 2015 INCOG 2014
Second line: methylphenidate의 효과가 없거나 유지가 어려운 경우 이차적으로 사용 고려
(1) catecholamine-augmenting agents (amantadine, bromocriptine, levodopa, bupropion, atomoxetine, modafinil)
Amantadine	Start: 100 mg bid Max: 200 mg bid (아침 & 점심)	TBI 후 PTA가 없고, 다른 약물에 반응하지 않는 환자에서 고려 (INCOG-C) VS or MCS 환자의 각성 및 의식 호전을 위해 고려 (INCOG-A)	Dizziness, insomnia, nausea	INCOG 2014 NGWG 2006 Giacino et al., 2012
Bromocriptine	Start: 2.5 mg bid Max: 10 mg bid (아침 & 점심)	주의력 결핍 호전에는 증거가 미약함 (level of evidence C) severe TBI 환자의 실행 기능 장애에 투여 고려 (level of evidence B)	Nausea, constipation	Whyte et al., 2008 McDowell, 1998
Levodopa/Carbidopa	Start: 50 mg/25 mg bid	TBI 환자에서 주의력 및 정보처리속도 회복에 관한 연구는 없음 실행 기능 장애에 amantadine과 병합 투여 고려 (level of evidence C)	Constipation, dizziness, orthostatic hypotension	Kraus MF & Maki PM, 1997
Bupropion	150mg daily	refractory motor restlessness 동반 시 투여 고려 (level of evidence C)	Dizziness, nervousness, insomnia, lightheadedness, nausea, headache, lowering seizure threhlod	Teng C et al., 2001
Atomoxetine	Start: 18 mg daily Max: 100 mg daily	TBI 환자의 주의력 결핍 호전에는 증거가 미약함 (level of evidence C)	Xerostomia, nausea, insomnia	Ripley DL, 2006 Ripley DL et al., 2014
Modafinil	Start: 100 mg bid Max: 200 mg bid (아침 & 점심)	chronic TBI 환자에서 주간 졸음을 동반한 기억력 및 주의력 장애에 투여 고려 (level of evidence C)	Headache, nausea	Saletu B et al., 1993 Teitelman E, 2001
(2) 주의력 장애가 cholinergic deficit을 반영하면 acetylcholinesterase inhibitor (donepezil, galantamine, rivastigmine)
Donepezil	Start: 5 mg daily Max: 10 mg daily	기억력 문제 동반 시 투여 권유 (level of evidence B)	Diarrhea, insomnia, nausea, headache	NGWG 2006 Khateb et al., 2005 Zhang et al., 2004
Galantamine	Start: 4 mg bid Max: 12 mg bid	기억력 저하 동반 시 투여 고려(Level of evidence C)	Diarrhea, nausea, vomiting	Tenovuo, 2005 Thomas WM et al., 2016
Rivastigmine	Start: 1.5 mg bid Max: 6 mg bid	moderate to severe memory impairment 환자에서 고려 (level of evidence B)	Diarrhea, nausea, vomiting, anorexia, dizziness	INESSS-ONF 2015 Tenovuo et al., 2009 Silver et al., 2009
(3) NMDA receptor antagonist (memantine)
Memantine	Start: 5 mg daily Max: 10 mg bid	TBI 환자에서 연구된 바 없음	Headache, diarrhea, dizziness
(4) 우울, 불안 등 다른 정서기능장애가 주의력에 영향을 끼치는 경우: serotonergic augmentation
Sertraline	Start: 25 mg daily Max: 200 mg daily	TBI 후 우울증에서 투여 고려 (Level of evidence C) 주의력 및 정보처리속도 회복에는 증거 부족 (level of evidence C)	Diarrhea, nausea, dizziness, abnormal ejaculation, reduced libido	INESSS-ONF 2015 Lee et al. 2005 Meythaler J et al. 2000
Fluoxetine	Start: 20 mg daily Max: 60 mg daily	TBI 후 우울 및 주의력 회복에 투여 고려 (level of evidence C)	Unusual dreams, decreased libido, anorexia, tremor	Horsfield et al., 2002
※ 약물 단일 요법의 효과가 부분적인 경우 다른 기전의 이차 약물을 추가하여 작용기전을 보완

참고문헌

Methylphenidate

Gualtieri CT, Evans RW. Stimulant treatment for the neurobehavioral sequelae of traumatic brain injury. Brain Inj. 1988;2(4):273–290.

INESSS-ONF Clinical Practice Guideline for the Rehabilitation of Adults with Moderate to Severe Traumatic Brain Injury. 2015

Jennie P, Mark B, Catherine WH et al. INCOG Recommendations for Management of Cognition Following Traumatic Brain Injury, Part II: Attention and Information Processing Speed. J Head Trauma Rehabil. 2014;29(4): 321–337.

Kaelin DL, Cifu DX, Matthies B. Methylphenidate effect on attention deficit in the acutely brain-injured adult. Arch Phys Med Rehabil. 1996;77:6–9.

Kim Y, Ko M, Na S, Park S, Kim K. Effects of single-dose methylphenidate on cognitive performance in patients with traumatic brain injury: a double-blind placebo-controlled trial. Clin Rehabil. 2006;20:24–30.

Plenger PM, Dixon CE, Castillo RM, Frankowski RF, Yablon SA, Levin HS. Subacute methylphenidate for moderate to moderately severe traumatic brain injury: a preliminary double-blind placebo-controlled study. Arch Phys Med Rehabil. 1996;77:536–540.

Speech TJ, Rao SM, Osmon DT, Sperry LT. A double-blind controlled study of methylphenidate treatment in closed-head injury. Brain Inj. 1993;7(4):333–338.

Warden DL, Gordon B, McAllister TW, et al. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006;23(10):1468–1501.

Whyte H, Hart T, Vaccaro M, et al. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional randomized, controlled trial. Am J Phys Med Rehabil. 2004;83(6):401–420.

Whyte J, Hart T, Schuster K, Fleming M, Polansky M, Coslett HB. Effects of methylphenidate on attentional function after traumatic brain injury: a randomized placebo-controlled trial. Am J PhysMed Rehabil. 1997;76(6):440–450.

Willmott C, Ponsford J. Efficacy of methylphenidate in the early rehabilitation of attention following traumatic brain injury: a randomized, crossover, double-blind, placebo controlled trial. J Neurol Neurosurg Psychiatry. 2009;80(5):552–557.

Amantadine

INESSS-ONF Clinical Practice Guideline for the Rehabilitation of Adults with Moderate to Severe Traumatic Brain Injury. 2015

DEBORAH L. WARDEN et al. Guidelines for the Pharmacologic Treatment of Neurobehavioral Sequelae of Traumatic Brain Injury. JOURNAL OF NEUROTRAUMA. Volume 23, Number 10, 2006, 1468–1501

Kraus MF, Maki P. The combined use of amantadine and l-dopa/carbidopa in the treatment of chronic brain injury. Brain Inj. 1997;11(6): 455–460.

Kraus MF, Smith GS, Butters M, et al. Effects of the dopaminergic agent and NMDA receptor antagonist amantadine on cognitive function, cerebral glucose metabolism and D2 receptor availability in chronic traumatic brain injury: a study using positive emission tomography (PET). Brain Inj. 2005;19(7): 471–479.

Nickels JL, Schneider WN, Dombovy ML, Wong TM. Clinical use of amantadine in brain injury rehabilitation. Brain Inj. 1994;8(8):709–718.

Schneider WM, Drew-Cates J, Wong TM, Dombovy ML. Cognitive and behavioral efficacy of amantadine in acute traumatic brain injury: an initial double-blind placebo controlled study. Brain Inj. 1999;13(11):863–872.

Giacino, J. T., Whyte, J., Bagiella, E., Kalmar, K., Childs, N., Khademi, A., . . . Sherer, M. (2012). Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med, 366(9), 819-826.

Bromocriptine

Whyte J, Vaccaro M, Grieb-Neff P et al. (2008). The effects of bromocriptine on attention deficits after traumatic brain injury: a placebo-controlled pilot study. Am J Phys Med Rehabil 87: 85–99.

McDowell S, Whyte J, D’Esposito M. Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients. Brain. 1998;121:1155–1164.

Levodopa

Kraus MF, Maki PM. The combined use of amantadine and l-dopa/carbidopa in the treatment of chronic brain injury. Brain Inj. 1997;11(6): 455–460.

Kraus MF, Maki PM. Effect of amantadine hydrochloride on symptoms of frontal lobe dysfunction in brain injury: case studies and review. J Neuropsychiatr Clin Neurosci. 1997;9(2):222–230.

Bupropion

Teng C, Bhalerao S, Lee A, et al. The use of buproprion in the treatment of restlessness after a traumatic brain injury. Brain Inj 2001;15:463-467.

Atomoxetine

Ripley DL. Atomoxetine for individuals with traumatic brain injury. J Head Trauma Rehabil. 2006;21(1):85–88.

Ripley DL, Morey CE, Gerber D, et al. Atomoxetine for attention deficits following traumatic brain injury: results from a randomized controlled trial. Brain Inj. 2014;28(12):1514–1522.

Modafinil

Saletu B, Saletu M, Grunberger J, et al. Treatment of the alcoholic organic brain syndrome: Double-blind, placebo-controlled controlled clinical, psychometric and electroencephalographic mapping studies with modafinil. Neuropsychobiology 1993; 27:26-39.

Teitelman E. Off-label uses of modafinil. Am J Psychiatry 2001;158:1341.

Donepezil

DEBORAH L. WARDEN et al. Guidelines for the Pharmacologic Treatment of Neurobehavioral Sequelae of Traumatic Brain Injury. JOURNAL OF NEUROTRAUMA. Volume 23, Number 10, 2006, 1468–1501

Khateb A, Ammann J, Annoni J et al. (2005). Cognition-enhancing effects of donepezil in traumatic brain injury. Eur Neurol 54: 39–45.

Zhang L, Plotkin R, Wang G et al. (2004). Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil 85: 1050–1055.

Galantamine

Tenovuo, O. (2005). Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury - Clinical experience in 111 patients. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 29(1) p.61-67.

Thomas W McAllister et al. Randomized Placebo-Controlled Trial of Methylphenidate or Galantamine for Persistent Emotional and Cognitive Symptoms Associated with PTSD and/or Traumatic Brain Injury. Neuropsychopharmacology. 2016 Apr;41(5):1191-8

Rivastigmine

INESSS-ONF Clinical Practice Guideline for the Rehabilitation of Adults with Moderate to Severe Traumatic Brain Injury. 2015

Tenovuo O, Alin J, Helenius H (2009). A randomized controlled trial of rivastigmine for chronic sequels of traumatic brain injury—what it showed and taught? Brain Inj 23: 548–558.

Silver JM, Koumaras B, Chen M, et al. Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology. 2006 Sep 12;67(5):748-55.

Sertraline

INESSS-ONF Clinical Practice Guideline for the Rehabilitation of Adults with Moderate to Severe Traumatic Brain Injury. 2015

Lee H, Kim S-W, Kim J-M, et al. Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury. Hum Psychopharmacol. 2005;20:97-104.

Meythaler J, Lawrence D, Devivo M, et al. Sertraline to improve arousal and alertness in severe traumatic brain injury secondary to motor vehicle crashes. Brain Inj 2000;15:321-331.

Fluoxetine

Horsfield, S.A.; Rosse, R.B.; Tomasino, V.; Schwartz, B.L.; Mastropaolo, J.; Deutsch, S.I. Fluoxetine’s effects on cognitive performance in patients with traumatic brain injury. Int. J. Psychiatry Med. 2002, 32, 337–344.