Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Rajesh R Tampi* and Michael B Maksimowski
Department of Psychiatry, MetroHealth, Cleveland, Ohio, USA
Corresponding Author : Rajesh R Tampi
Professor of Psychiatry, Case Western Reserve University School of Medicine
Vice Chairman for Education Program Director, Psychiatry Residency, Department of Psychiatry, MetroHealth
2500 Metrohealth Drive, Cleveland, Ohio, 44109, USA
Tel: (203) 809 5223
E-mail: rajesh.tampi@gmail.com
Received: December 15, 2015; Accepted: December 18, 2015; Published: December 25, 2015
Citation: Tampi RR, Maksimowski MB (2015) Are Stimulants Beneficial In Individuals with Traumatic Brain Injury?. J Addict Res Ther 6:e133. doi: 0.4172/2155-6105.1000e133
Copyright: © 2015 Tampi RR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Related article at Pubmed, Scholar Google

Visit for more related articles at


Traumatic Brain Injury (TBI) can be defined as an insult to the brain from an external mechanical force that can result in temporary or permanent impairments in cognitive, functions and behaviours [1]. It is estimated that an average of 1-2 million individuals each year sustain a TBI in the United States [2,3] The physical, cognitive and behavioural limitations experienced from TBI often become chronic, impacting an individual’s daily functioning, relationships and employment [4].

Despite our knowledge of the epidemiology, pathophysiology, and multifaceted consequences of TBI, there is no standardized protocol or FDA-approved medication to pharmacologically treat cognitive and behavioral symptoms associated with TBI [5] Warden et al. completed a comprehensive literature search and did not find sufficient evidence to support any treatment standards [6]. Multiple studies have shown effectiveness of SSRIs and stimulants for treatment of depressive and cognitive symptoms associated with TBI, respectively [7]. The theoretical basis for studying stimulants in individuals with TBI has always been the large body of research supporting efficacy of stimulants in individuals with Attention Deficit Hyperactivity Disorder (ADHD) [8].

Dopamine is considered an essential neurotransmitter in attention processing [9]. Stimulants are known to enhance dopaminergic activity within many brain areas but especially within the striatum and frontal cortex, regions theorized to be essential for attention [10]. TBI often results in damage to brain regions abundant with dopaminergic receptors as well as dopamine-producing areas [11] This includes the frontal lobe, which is more susceptible to traumatic forces exerted by head injury than other lobes [12,13].
Evidence for Using Stimulants

A systematic review of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration from December 4, 2014, indicates that there are a total of sixteen RCTs on the use of stimulants in individuals with TBI. Of the sixteen studies, three studied pediatric populations [14-16]. The majority of studies assessed methylphenidate (MPH) [13,17-28] while one assessed dexamphetamine and MPH16, and one assessed modafanil [29]. Over half of the studies utilized a cross-over design [14-16,24-29]. Patients ranged in severity of TBI from mild to severe, as well as in latency between TBI diagnosis and study treatment. Dosing of MPH ranged from one-time doses of 20 mg to twice-daily doses of 0.3 mg/kg. The one study that assessed dexamphetamine adhered to patients’ current dosing, which ranged from 5 to 10 mg twice daily. In the one study that assessed modafanil, dosing began at 100 mg daily which was titrated to 400 mg daily over 14 days [29]. Quantitative measures included scales of arousal, depression, and behaviour, as well as attentional tasks to assess reaction time and accuracy. Fourteen of the 16 studies utilized placebo as the only comparator to stimulant. One study compared MPH to sertraline and placebo22 and another study compared MPH or dexamphetamine to placebo [16].

Seven studies showed significant improvements in reaction time [14,20,21,23-25] while four studies showed significant improvements in accuracy [20,21,24,27]. One study reported significant improvements in caregiver-reported attentional behavioral scales [24]. One study found significantly decreased length of hospital stay with treatment [19]. One study showed significant improvements in depressive symptoms [22]. One study found a significantly decreased duration of hospital stay for patients given MPH [19]. Only one of the three paediatric studies found a significant benefit (attention tasks) with stimulant use compared to placebo [15]. Two studies included follow-up; one found significant differences in disability ratings, attention-concentration, and motor memory at 30 days but not 90 days23, while the other found no significant differences between stimulant and placebo groups at 1 year.27 Of note, the majority of studies demonstrated significant treatment effects immediately (i.e., within minutes to hours) after first-time administration of the tested stimulant. Four of the sixteen studies (2 adult, 2 pediatric) did not find benefit for stimulants when compared to placebo [15,16,18,29]. Two studies found no significant differences in self-reported side effects [17,26] although one of the two studies showed a significant difference in mean arterial pressure [17].

Stimulants were well tolerated in thirteen of the sixteen studies with the side-effect profile of the drug being similar to that of placebo. Six studies did not comment on whether side effects were or were not observed.
Summary of Evidence

The available data from a systematic review of the literature indicates that stimulants can improve attention (speed of information processing, reaction time and task performance) in individuals with TBI, immediately and for a short term period. Stimulants were also noted to reduce length of hospital stay and improve depressive symptoms. These medications were fairly well-tolerated in the studies.

Based on our current review, it would be prudent to state that stimulants can be recommended for immediate and short term treatment of attentional deficits in individuals with TBI. However, it remains to be determined whether stimulants have any benefit on other cognitive domains, mood symptoms, anxiety symptoms or behavioral issues in individuals with TBI. Additionally, the long-term treatment efficacy of these drugs in individuals with TBI is not evident at the current time.

There is evidence to suggest immediate and short-term efficacy for psychostimulants in the treatment of attentional deficits in individuals with TBI. Stimulants appear to be well-tolerated in the majority of the studies included in this review. Data from well conducted larger and longer term RCTs will be helpful in determining whether stimulants have efficacy on different cognitive, behavioral and functional domains in individuals with TBI.

  1. Capruso DX, Levin HS. Neurobehavioral sequelae of head injury. Head injury.4th ed. New York: McGraw-Hill. 2000: 525-553.

  2. Thurman D, Guerrero J (1999) Trends in hospitalization associated with traumatic brain injury.below JAMA 282: 954-957.

  3. Thurman DJ, Alverson C, Dunn KA, Guerrero J, Sniezek JE (1999) Traumatic brain injury in the United States: A public health perspective.below J Head Trauma Rehabil 14: 602-615.

  4. Prigatano GP (1999) Principles of neuropsychological rehabilitation. Oxford University Press.

  5. National GC. Traumatic brain injury medical treatment guidelines.

  6. Neurobehavioral Guidelines Working Group, Warden DL, Gordon B, McAllister TW, Silver JM, et al. (2006) Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury.below J Neurotrauma 23: 1468-1501.

  7. Silver JM, McAllister TW, Arciniegas DB (2009) Depression and cognitive complaints following mild traumatic brain injury.below Am J Psychiatry 166: 653-661.

  8. National resource center on AD/HD. Managing Medication for Adults with ADHD Web site.

  9. Brennan AR, Arnsten AF (2008) Neuronal mechanisms underlying attention deficit hyperactivity disorder: the influence of arousal on prefrontal cortical function.below Ann N Y AcadSci 1129: 236-245.

  10. Schiffer WK, Volkow ND, Fowler JS, Alexoff DL, Logan J, et al. (2006) Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine.below Synapse 59: 243-251.

  11. Chudasama Y, Robbins TW (2006) Functions of frontostriatal systems in cognition: comparative neuropsychopharmacological studies in rats, monkeys and humans.below BiolPsychol 73: 19-38.

  12. Benson DF, Blumer D. Psychiatric aspects of neurological disease. Grune& Stratton; 1982.

  13. Clifton GL, Grossman RG, MakelaME, Miner ME, Handel S, Sadhu V (1980) Neurological course and correlated computerized tomography findings after severe closed head injury. J Neurosurg. 52: 611-624.

  14. Mahalick DM, Carmel PW, Greenberg JP, Molofsky W, Brown JA, et al. (1998) Psychopharmacologic treatment of acquired attention disorders in children with brain injury.below PediatrNeurosurg 29: 121-126.

  15. Williams SE, Ris MD, Ayyangar R, Schefft BK, Berch D (1998) Recovery in pediatric brain injury: is psychostimulant medication beneficial?below J Head Trauma Rehabil 13: 73-81.

  16. Nikles CJ, McKinlay L, Mitchell GK, Carmont SA, Senior HE, et al. (2014) Aggregated n-of-1 trials of central nervous system stimulants versus placebo for paediatric traumatic brain injury--a pilot study.below Trials 15: 54.

  17. Alban JP, Hopson MM, Ly V, Whyte J (2004) Effect of methylphenidate on vital signs and adverse effects in adults with traumatic brain injury.below Am J Phys Med Rehabil 83: 131-137.

  18. Hart T, Whyte J, Ellis C, Chervoneva I (2009) Construct validity of an attention rating scale for traumatic brain injury.below Neuropsychology 23: 729-735.

  19. Khalili HA, Keramatian K (2008) Effect of methylphenidate in patients with acute traumatic brain injury; a randomized clinical trial. Progress in Neurotherapeutics and Neuropsychopharmacology.3: 189-197.

  20. Kim J, Whyte J, Patel S (2012) Methylphenidate modulates sustained attention and cortical activation in survivors of traumatic brain injury: A perfusion fMRI study. Psychopharmacology (Berl) 222: 47-57.

  21. Kim YH, Ko MH, Na SY, Park SH, Kim KW (2006) Effects of single-dose methylphenidate on cognitive performance in patients with traumatic brain injury: a double-blind placebo-controlled study.below ClinRehabil 20: 24-30.

  22. Lee H, Kim SW, Kim JM, Shin IS, Yang SJ, et al. (2005) Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury.below Hum Psychopharmacol 20: 97-104.

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

  24. Whyte J, Hart T, Schuster K, Fleming M, Polansky M, et al. (1997) Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial.below Am J Phys Med Rehabil 76: 440-450.

  25. Whyte J, Hart T, Vaccaro M, Grieb-Neff P, Risser A, et al. (2004) Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial.below Am J Phys Med Rehabil 83: 401-420.

  26. Willmott C, Ponsford J, Olver J, Ponsford M. (2009) Safety of methylphenidate following traumatic brain injury: Impact on vital signs and side-effects during inpatient rehabilitation. J Rehabil Med. 41: 585-587.

  27. Willmott C, Ponsford J (2009) Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: A randomised, crossover, double blind, placebo controlled inpatient trial. J NeurolNeurosurg Psychiatry. 80: 552-557.

  28. Gualtieri CT, Evans RW (1988) Stimulant treatment for the neurobehaviouralsequelae of traumatic brain injury.below Brain Inj 2: 273-290.

  29. Jha A, Weintraub A, Allshouse A, Morey C, Cusick C, et al. (2008) A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury.below J Head Trauma Rehabil 23: 52-63.

Select your language of interest to view the total content in your interested language
Share This Article
Relevant Topics
Recommended Journals
Disc Engineering Journals
Disc Surgery Journal
Disc Journal of Nanomedicine & Biotherapeutic Discovery
  View More»
Recommended Conferences
Disc International Conference on Physics
New Orleans, USA
Disc 5th Agriculture &Horticulture Conference
June 27-29, 2016 Cape Town, South Africa
Disc 5th Tissue Science and Regenerative Medicine Conference
September 12-14, 2016 Berlin, Germany
Disc Geophysics Conference
Sept 29-Oct 1, 2016 Vancouver, Canada
Disc 5th Alzheimer’s Disease & Dementia Conference
Sept 29-Oct 1, 2016 London, UK
Disc Human Genetics Conference
Oct 31- Nov 02, 2016 Valencia, Spain
Disc 2nd Global Summit on Plant Science
October 31-November 02, 2016 Baltimore, USA

2nd Pregnancy and Child Health
Sao Paulo, Brazil

Article Tools
Disc Export citation
Disc Share/Blog this article
Article usage
  Total views: 0
  [From(publication date):
- - May 24, 2016]
  Breakdown by view type
  HTML page views :
  PDF downloads :

Post your comment

captcha   Reload  Can't read the image? click here to refresh

OMICS International Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
OMICS International Conferences 2016-17
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish


1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A


1-702-714-7001Extn: 9037

Business & Management Journals



1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw


1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson


1-702-714-7001Extn: 9042

Engineering Journals

James Franklin


1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason


1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa


1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl


1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner


1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green


1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison


1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna


1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T


1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon


1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry


1-702-714-7001 Extn: 9042

© 2008-2016 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version