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Effects of Methylphenidate on Attention Deficits After Traumatic Brain Injury

A Multidimensional, Randomized, Controlled Trial

Whyte, John, MD, PhD; Hart, Tessa, PhD; Vaccaro, Monica, MS; Grieb-Neff, Patricia, MA; Risser, Anthony, PhD; Polansky, Marcia, ScD; Coslett, H. Branch, MD

American Journal of Physical Medicine & Rehabilitation: June 2004 - Volume 83 - Issue 6 - p 401-420
doi: 10.1097/01.PHM.0000128789.75375.D3
Research Articles: Brain Injury
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Whyte J, Hart T, Vaccaro M, Grieb-Neff P, Risser A, Polansky M, Coslett HB: Effects of methylphenidate on attention deficits after traumatic brain injury: A multidimensional, randomized, controlled trial. Am J Phys Med Rehabil 2004;83:401–420.

Objective: To evaluate the effects of methylphenidate on a variety of aspects of attention, ranging from laboratory-based impairment measures to caregiver ratings and work productivity, in individuals after traumatic brain injury.

Design: A total of 34 adults with moderate to severe traumatic brain injury and attention complaints in the postacute phase of recovery were enrolled in a 6-wk, double-blind, placebo-controlled, repeated crossover study of methylphenidate, administered in a dose of 0.3 mg/kg/dose, twice a day. A wide range of attentional measures was gathered weekly, including computerized and paper-and-pencil tests of attention, videotaped records of individual work in a distracting environment, real-time observational scoring of attentiveness in a classroom environment, and caregiver and clinician rating scales of attentiveness. Participants also attempted to guess their drug condition each week. Data from the first ten participants were used for pilot purposes, to develop attentional factors for composite scoring, and to identify attentional dimensions suggestive of a treatment effect for independent replication. The remaining 24 participants' results were used to confirm potential treatment effects seen in the pilot sample, using Wilcoxon's signed-ranks test on composite factor scores and individual variables.

Results: A total of 54 dependent variables were reduced to 13 composite factors and 13 remaining individual variables. Of the 13 attentional factors, five showed suggestive treatment effects in the pilot sample. Of these, three showed statistically significant treatment effects in the replication sample: speed of information processing (effect sizes, &minus;0.06 to 0.48; P < 0.001), attentiveness during individual work tasks (effect sizes, 0.15–0.62; P = 0.01), and caregiver ratings of attention (effect sizes, 0.44–0.50; P = 0.01). Of the individual variables, four showed suggestive treatment effects in the pilot sample, but only one showed significant treatment effects in the replication sample: reaction time before errors in the Sustained Attention to Response Task (effect size, 0.20; P = 0.03). No treatment-related improvement was seen in divided attention, sustained attention, or susceptibility to distraction. None of the variables showed suggestive or definite negative treatment effects. Effect sizes for those performance measures positively affected by methylphenidate were in the small to medium range and included both impairment and activity level measures. Improvements in processing speed did not seem to come at the expense of accuracy.

Conclusions: Methylphenidate, at 0.3 mg/kg/dose, given twice a day to individuals with attentional complaints after traumatic brain injury, seems to have clinically significant positive effects on speed of processing, caregiver ratings of attention, and some aspects of on-task behavior in naturalistic tasks. Further research is needed to identify the optimal dose and to extend these findings to less carefully selected individuals.

From the Moss Rehabilitation Research Institute, Albert Einstein Healthcare Network, Philadelphia, Pennsylvania (JW, TH, MV, PGN, AR, HBC); the Department of Rehabilitation Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania (JW, TH); the Department of Symptom Research, University of Texas, M. D. Anderson Cancer Center, Houston, Texas (AR); the Department of Biostatistics, Drexel University, Philadelphia, Pennsylvania (MP); and the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (HBC).

Disclosures:

Supported, in part, by grant R01NS39163 from the National Institute on Neurological Diseases and Stroke, National Institutes of Health, and grant R24HD39621 from the National Center for Medical Rehabilitation Research, National Institute on Child Health and Human Development, National Institutes of Health.

Correspondence:

All correspondence and requests for reprints should be addressed to John Whyte, MD, PhD, Moss Rehabilitation Research Institute, 1200 West Tabor Road, Suite 213, Philadelphia, PA 19141.

© 2004 Lippincott Williams & Wilkins, Inc.