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Impact of Early Pharmacological Treatment on Cognitive and Behavioral Outcome After Traumatic Brain Injury in Adults: A Meta-Analysis

Wheaton, Patricia BA(Hons)*; Mathias, Jane L. BA, BA(Hons), PhD*; Vink, Robert BSc, BSc(Hons), PhD

Journal of Clinical Psychopharmacology: October 2009 - Volume 29 - Issue 5 - p 468-477
doi: 10.1097/JCP.0b013e3181b66f04
Review Article

Early pharmacological treatment has the potential to reduce some of the disabling cognitive and behavioral problems that result from traumatic brain injury (TBI). Although a large number of treatments have been developed, clinical research has yielded inconsistent findingfss with respect to the effectiveness of these pharmacological treatments on cognitive and behavioral outcomes. Furthermore, their relative efficacy has not been evaluated, thereby hindering advances in the treatment of TBI. A meta-analysis of research that examined the impact of pharmacological treatments on cognitive and behavioral outcomes in the early stages after TBI between January 1980 and May 2008 was therefore undertaken. The PubMed and PsycINFO databases were searched using 35 terms. All articles were screened using detailed inclusion criteria. Weighted Cohen's d effect sizes, percent overlap statistics, and fail-safe N statistics were calculated for each pharmacological agent. Studies that used different experimental designs were examined separately. Eleven pharmacological treatments were investigated by 22 clinical studies, comprising 6472 TBI patients in the treatment groups and 6460 TBI controls. One dopamine agonist (amantadine) and 1 bradykinin antagonist (CP-0127 [Bradycor]) produced marked treatment benefits (d ≥ 0.8) for a single measure of arousal (Glasgow Coma Scale). Notably, drug dosage and the measure chosen to assess outcome influenced the probability of finding a treatment benefit.

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From the Schools of *Psychology, and †Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.

Received October 19, 2008; accepted after revision July 2, 2009.

Reprints: Patricia Wheaton, BA(Hons), School of Psychology, University of Adelaide, South Australia, Australia 5005 (e-mail:

This research was supported by the Neurosurgical Foundation of Australia and the Faculty of Health Sciences of The University of Adelaide in the form of a divisional scholarship to Patricia Wheaton.

Portions of this work were presented at the Seventh World Congress on Brain Injury of the International Brain Injury Association, Lisbon, Portugal, April 9 to 12, 2008.

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the Journal's Web site (

© 2009 Lippincott Williams & Wilkins, Inc.