Communication
Study of the Use of Amphetamine in the Treatment of Aphasia
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In a recent study of 21 subjects with moderate to severe aphasia deficits, administration of dextroamphetamine paired with speech/language treatment during the subacute recovery period accelerated the rate of aphasia recovery, as assessed by a reliable test of communication ability. One week after drug sessions ended, there was a significant difference in recovery between the groups. There was also a significant difference in the number of subjects who achieved the predetermined clinical change score of 15 points. The 16.7-point change in PICA overall score in the dextroamphetamine group with only 10 drug treatment sessions and 33 total hours of language therapy over the 5-week study period compares favorably with previous aphasia efficacy studies that used the PICA as the primary outcome measure at a similar period of study entry. Subjects in the Veteran’s Administration Cooperative Study, who were also entered in the subacute recovery period, made an 18.2-point PICA overall change after being treated over 12 weeks and receiving between 96 and 120 hours of treatment. These results confirm previous clinical work by ourselves and others of a facilitative effect of dextroamphetamine on rate of behavioral recovery after occlusive stroke.
It cannot be determined from the present study whether recovery endures after drug treatment. Although at the 6-month follow-up the numerical difference in gain scores between the groups increased, the difference was not significant when corrected for multiple comparisons. In this study we purposely chose a conservative approach to the data analysis. However, incorporating this adjustment increases the risk of not detecting an effect when an effect actually exists. The power of this study to detect differences is also limited because the sample size was smaller than projected.
The results of this study extend previous clinical findings in motor recovery to recovery from aphasia and suggest that the dextroamphetamine effect found in animal models of stroke recovery has application to human rehabilitation. When we consider the rather moderate effects of the low dose of dextroamphetamine used in this protocol in severely aphasic subjects over 10 paced dextroamphetamine sessions with 33 hours of speech/language therapy, we have to ask what more drug and more treatment might do. It is also noteworthy that patients enrolled into this dextroamphetamine protocol suffered no adverse reactions, a finding that we have previously reported.
This study is limited because of the small group of aphasic subjects and may not represent all stroke patients. However, because many of the patients we studied had severe aphasic deficits at entry, effects in this small sample would appear to be meaningful. Additionally, from this small sample it is not possible to specify whether aphasia type predicts response. In this particular group of aphasic patients, day of study initiation (up to day 45) did not determine response or nonresponse. It should be noted that this treatment is not equally effective for all deficits, a finding also observed in the animal model. Patients with an initial apraxia of speech so severe that they had no speech output did not recover verbal ability as a means of communication, although other language areas such as writing were significantly enhanced. Larger samples to allow for greater stratification in terms of severity, types of aphasia, and age would better characterize response or nonresponse.
Conclusions
Administration of dextroamphetamine paired with 10 1-hour sessions of speech/language therapy facilitated recovery from aphasia in a small group of patients in the subacute period after stroke. Neuromodulation with dextroamphetamine, and perhaps other drugs that increase central nervous system noradrenaline levels, may facilitate recovery when paired with focused behavioral treatment.
Discussion
While the study of the relation between aphasia and areas of cortical injury originated over a century ago, the attempted treatment of aphasia has a surprisingly short history. The study considered the first investigation of "treatment efficacy" in ST used a no-treatment control group and was published in 1964. Unlike other health care specialties, ST was founded on educational principles, "the aphasic patient was to be taught language just as a child is taught."6 Only in the 1970s were outcome studies begun and reviews of the few controlled experiments describe the results as "unimpressive."7 The recent review and analysis by the Cochran group8 of the controlled studies on the efficacy of ST summarized this outcome literature as "not been shown either to be clearly effective or clearly ineffective." Given this background, the studies by Walker-Batson and colleagues are unique compared to those typically conducted on the efficacy of rehabilitation treatments a decade earlier.
Excerpted from A Double-Blind, Placebo-Controlled Study of the Use of Amphetamine in the Treatment of Aphasia by Delaina Walker-Batson, PhD; Sandra Curtis, MA; Rajeshwari Natarajan, PhD; Jean Ford, PhD; Nina Dronkers, PhD; Eva Salmeron, MD; Jenny Lai, MD; D. Hal Unwin, MD
From The Stroke Center-Dallas, Department of Communication Sciences & Disorders, Texas Woman’s University (D.W.-B., S.C., J.F.), The Mobility Foundation Center and Department of Neurology, University of Texas Southwestern Medical Center (D.W.-B., D.H.U.), and the Department of Statistical Science, Southern Methodist University (R.N.), Dallas, Tex; the Department of Physical Medicine and Rehabilitation, University of Texas Health Science Center at Houston (E.S., J.L.); and Center for Aphasia and Related Disorders, VA Northern California Health Care System (N.D.), Martinez, Calif.
Direct correspondence to Dr Delaina Walker-Batson, The Stroke Center-Dallas, Department of Communication Sciences & Disorders, Texas Woman’s University, 1810 Inwood Road, Dallas, TX 75235-7299.E-mail DWalkerBatson@twu.edu
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