Drugs and Recovery: A Challenge for a Few?
To the Editor:
I read with great interest the recent article by Walker-Batson and colleagues,1 in which the authors show that the administration of dextroamphetamine and speech/language therapy facilitated recovery from aphasia.
We also investigated the efficacy of high-dose bromocriptine, prescribed according to a dose-escalating protocol, combined with speech therapy in a double-blind study.2 Patients showed a significant improvement in language (verbal latency, repetition, reading comprehension, dictation, and free speech) during treatment, yet we considered the study negative. The high frequency of contraindication to bromocriptine administration in the enrollment phase (44% of the aphasic patients) allowed us to treat only a small sample of patients. Moreover, we observed an elevated occurrence of side effects during the active phase of the drug.
Remarkably, none of the patients enrolled into the study of Walker-Batson et al had adverse reactions, and this makes the dextroamphetamine not only one of the most successful agents used in the treatment of aphasia but also the safest. Nevertheless, the small number of patients enrolled (n=25), in comparison with the relatively long study period (4 years) and the huge number of patients screened (n=850), confirms the necessity of being very selective before giving drugs that might enhance stroke recovery but also have serious side effects.
Therefore, we would like to stress that, even in presence of a relatively safe drug such as dextroamphetamine, to date the pharmacotherapy of stroke recovery remains a “luxury” that only few patients enjoy. This fact per se precludes studies from shifting focus from a condition of “explorative” studies to a wider condition.
Moreover, this strengthens the paradox that, despite the large number of stroke victims, we still have a small number of patients who might benefit by a specific treatment in both the acute and chronic phases.
While we agree with Drs Altieri, Di Piero, and Lenzi that the use of dextroamphetamine is not ready for wide acceptance as a standard of care for poststroke deficits, we disagree with their reasons. It is true that in our recently published study in aphasia we had specific exclusion criteria. We considered the exclusions necessary for an initial efficacy study of this type. However, the number of patients screened (n=850) compared with those enrolled (n=25) is fairly typical of stroke trials in general. The primary exclusion for the patients that we screened was history of a previous stroke with residual deficits. Those patients with radiological evidence of a previous stroke that was clinically silent were included in our sample. The second major exclusion for the patients we screened was aphasia so mild that subjects did not meet our inclusion definition. Included in our sample were many patients with medically complicated histories, ie, cardiovascular surgery, diabetes, and hypertension. In fact, the majority of the patients in our study had history of hypertension controlled by medication (>160/100 mm Hg). Thus, although admittedly small, our sample was special only in that it required a single stroke. The low-dose amphetamine (10 mg) that we administered was safe for a broad range of patients, a finding that we have previously reported (D.H. Unwin, MD, and D. Walker-Batson, PhD, unpublished data, 2000).
The reason that the use of dextroamphetamine is not ready for broad application is not that only a select group of patients can enjoy the effects. The reason that pharmacotherapy with the use of dextroamphetamine is not ready to become a standard of care is that there are still many gaps in our knowledge. Unanswered questions include the following: How long after stroke can amphetamine be administered and have an effect? What are the dosage and the number of drug administrations needed to provide optimum recovery? What is the amount of use-dependent practice or retraining that must be paired with the pharmacological intervention for optimal recovery? We are encouraged that ongoing trials (supported by the National Institutes of Health and the Medical Research Council of Canada) are exploring the efficacy of dextroamphetamine to enhance recovery from stroke. It is hoped that, in time, with collaborations between the basic science laboratory and clinicians, pharmacotherapy will become a standard of care for poststroke deficits.