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Horn, Lawrence J. MD

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Journal of Head Trauma Rehabilitation: August 2002 - Volume 17 - Issue 4 - p v-vi
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One of the most challenging but important roles for the brain injury rehabilitation medicine specialist has been the appropriate use of pharmacotherapy for people with brain injuries. This applies not only to the prescription of drugs that may improve cognitive, neurobehavioral, or other functions but also to the elimination of medications that may impede recovery. Over the past 20 years, we have learned a great deal about the neurochemical systems involved in acute injury and which systems and subsystems are involved, at least in some way, with certain specific behaviors or neurological activities. Nonetheless, many of the drugs we use, we use on the basis of analogous data for other populations of individuals with other diseases or disabilities. It is interesting that now, when presenting a lecture on brain injury, the list of questions from the sponsoring authority includes not only those related to any “financial interest” in proprietary drugs, but also whether “non-FDA-approved” use will be discussed. Virtually all the psychopharmacological interventions we have are based on “non-FDA-approved” use. That is, although the drugs are usually FDA approved for something, nowhere is there a specific approved use to “wake up” the minimally conscious patient, shorten posttraumatic amnesia, improve memory, facilitate controlled behavior, treat neglect, or facilitate motor recovery in traumatic brain injury (TBI). This underscores the fact that “evidence-based” pharmacological brain injury rehabilitative medicine remains in relative infancy.

The articles in this issue provide updated reviews and original research on specific pharmacological agents. Dr. Glenn begins the issue by discussing the general “differential diagnosis” approach to the individual with TBI. He focuses less on the pharmacological management than on the variety of other variables requiring attention from the managing physician. His article helps the clinician to clearly identify target behaviors and functions before implementing medications.

The next article, by Dr. Whyte et al, is both a thorough review of evidence-based data about psychostimulants and a presentation of some pilot data on methylphenidate. Studies of both methylphenidate and amphetamine are reviewed. The pilot study seeks to more clearly identify those measures of neuropsychological function specific to TBI that may respond to methylphenidate. The study also incorporates more global functional measures. Dr. Whyte concludes the article with several pertinent questions about how best to study the psychostimulants. However, the studies reviewed and the one presented do support the potential beneficial effects of these medications in brain injury rehabilitation.

Dr. Meythaler and his colleagues present a very exciting original research study that for the first time, in a meticulous double-blind placebo-controlled design, demonstrates the clear effectiveness of amantadine for improving several measurable areas of performance in the first 12 weeks after brain injury. Although amantadine has been used to enhance generic cognitive function for many years, this use has been supported only by small, rarely controlled, studies or case reports…until now. Unfortunately, because of the design of the study, it is difficult to distinguish the effectiveness of the drug in the early phases of recovery from spontaneous recovery during the interval when the latter is most robust. “Spillover” of the early group into the late group confounds this type of analysis. Nonetheless, this is the first study to demonstrate the effectiveness of amantadine for TBI pharmacological rehabilitation with a rigorous evidence-based design.

The remaining four articles in this issue are reviews of commonly used classes of medications. Dr. Blount et al reviews the cholinergic agents available and the data to support their use in TBI, primarily for memory impairments. Unfortunately, there are few well-controlled/designed studies specific to people with TBI, and much of the research on effectiveness is from people with dementia. Thus far, there is no clear evidence to support the use of newer agents such as donepezil for memory impairment after TBI. However, these medications are generally safe and anecdotal support for their use persists.

Dr. Zafonte and his colleagues provide a very detailed review of serotonin agonists, particularly the selective serotonin reuptake inhibitors, to help guide the clinician in using these medications for neurobehavioral and emotional sequelae of TBI. Included is a thorough discussion of serotonin physiology. From a clinical perspective, the need to carefully titrate the dose and the admonition against sudden discontinuation are very useful practical points.

Finally, the review article by Thaxton and Myers addresses the clinical and pharmacological management of sleep disorders. Dysfunctional sleep is one of the most common confounding variables in the assessment and management of cognitive, behavioral, and affective impairment after brain injury. The authors provide a clinical approach to assessing sleep disturbances and suggestions for management, including, but not limited to, pharmacological agents.

Overall it is hoped that this issue of JHTR (17:4), combining reviews and original research, provides a useful condensed update on pharmacological rehabilitation after brain injury.

© 2002 Lippincott Williams & Wilkins, Inc.