No Side Effects After Low-Dose Amphetamine Administration in Stroke Rehabilitation
To the Editor:
We have previously reported the use of dextroamphetamine to enhance recovery from motor and language deficits subsequent to stroke.1 2 However, some clinicians have questioned the safety of the use of a stimulant drug in stroke patients. We have now followed a series of patients with no side effects of low-dose amphetamine administration as an adjunct to stroke rehabilitation. The protocol, which we have found to be safe, specifies that patients be entered between days 10 and 40 after stroke onset. Hemiplegic/aphasic patients are administered an oral dose of 10 mg of dexedrine or placebo 30 minutes before relevant therapies for 10 sessions. We monitor blood pressure of all patients before and within each treatment session and document any adverse reactions.3 We found no adverse reaction notations in any chart in a series of patients followed over a 1-year. Additionally, there were no differences in the blood pressure readings between drug- versus placebo-treated groups. Following are our subject definitions and blood pressure comparisons.
Forty-four stroke subjects with hemiplegia and/or aphasia and a radiologically verified lesion were studied. Criteria for entry into the study required that subjects have a single unilateral thromboembolic infarction and hemiplegia and/or aphasia, as defined by impairment level assessments. Exclusion criteria specified that none of the subjects have a terminal medical condition such as AIDS or cancer, other coincident neurological disease, history of psychiatric illness or extensive alcohol or drug abuse, unstable cardiac dysrhythmia or hypertension not controlled by medication (160/100 mm Hg), or untreated hyperthyroidism. Additionally, subjects could not be receiving α-adrenergic antagonists or agonists, major or minor tranquilizers, or be aged >80 years. Written informed consent was obtained from each subject before the study, and the research protocol was approved by the institutional review for human subjects at each of the participating medical centers.
The study group consisted of 28 amphetamine and 16 placebo patients. The mean age of the treatment group was 61 years; the mean age of the placebo group was 61 years. There were 11 men and17 women in the amphetamine group and 9 men and 7 women in the placebo group. In this blinded study, patients were entered between days 16 and 42 after onset and received an oral dose of 10 mg of amphetamine (dexedrine) or placebo on an alternating cycle of every third/fourth day for 10 sessions, paired with relevant therapies. Thirty minutes after drug/placebo administration, subjects began 1 hour to 1 hour 45 minutes of physical and/or language therapy, depending on their deficits. Documentation of side effects was made for all subjects across the study period. Blood pressure was monitored before and during the 10 treatment sessions in all subjects. Median systolic and diastolic blood pressure measurements were compared in the amphetamine- and placebo-treated subjects. The Wilcoxon rank sum test was performed on the difference of the medians between the 2 groups. Blood pressure readings of all subjects at baseline and across the 10 sessions were analyzed. Comparisons were made before drug administration (baseline) and 90 minutes into therapy sessions (within session) (see the Table⇓ for median scores for each group). There was not a significant difference from baseline to within-session measure on either systolic (P=0.1912) or diastolic (P=0.4056) differences for the 2 groups. In addition, at no time during the 12-month course of the study was there documentation of any negative event that could be attributed to amphetamine administration.
These data suggest that in patients with well-controlled hypertension, the effects of low-dose amphetamine administration are negligible. The data also support previous findings which suggest that toxic symptoms with doses <15 mg are rare.3 The subjects in this study may not represent all types of stroke subjects because of our careful exclusion criteria and patient screening. However, we did have patients with severe neurological impairments and other concomitant medical conditions who tolerated this low alternating dose without report of negative side effects.
This research was supported in part by the Mobility Foundation, Dallas, Texas; The Moody Foundation, Galveston, Texas; and National Institutes of Health grant 1-R01-DC02044.
- Copyright © 2000 by American Heart Association
Walker-Batson D, Smith P, Curtis S. Unwin H, Greenlee RG. Amphetamine paired with physical therapy accelerates motor recovery after stroke: further evidence. Stroke. 1995;26:2254–2259.
Walker-Batson D, Curtis S, Wolf T, Porch B. Amphetamine treatment accelerates recovery from aphasia. Brain Lang. 1996;55:27–29.
Physician’s Desk Reference. 46th ed. Oradell, NJ: Medical Economics Company Inc; 1992.