Interaction between psychological and pharmacological treatment in cognitive impairment. Design and methods of a randomized controlled trial on early speech and language therapy in patients with acute stroke and aphasia. A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. A prospective, randomized, parallel group, controlled study of the effect of intensity of speech and language therapy on early recovery from poststroke aphasia. Long-term and high-dose piracetam treatment of Alzheimer's disease.
In contrast to other kinds of psychotropic drugs, nootropics or cognition enhancing drugs may be indicated, not for the direct treatment of the pathology itself, but for improving or restoring the remaining brain functions. Brain functions are normally trained during various kinds of non-medical therapy, such as physiotherapy, speech therapy, occupational therapy, memory training etc... In research little attention has been paid to the combination of both kinds of therapeutic approaches, probably because of the important methodological difficulties. This combination however, offers various interesting perspectives: L. ISRAEL examined in two placebo-controlled studies the effects of either 160 mg/d of ginkgo biloba extractum (GBE) or piracetam 2.4 or 4.8 g/d, combined with a memory training program, in nondemented patients complaining of memory problems. The results of both studies suggest that nootropic drug treatment and memory training have each an effect on different cognitive functions and, hence, are complementary. Some functions, like attention/perception in the GBE study and learning in the piracetam study, seem to benefit from both treatments, suggesting a mutually potentiating effect of drug treatment and training. This potentiation is very clear in the treatment of dyslexic children: in a placebo-controlled study piracetam 3.3 g/d, in combination with normal school teaching and more specific logopedic therapy, allowed a normal progression during the full school year in reading accuracy and reading comprehension, while the placebo treated children getting a similar training progressed only with 50%. Recently promising results were obtained in the treatment of dysphasic patients with a combination of speech therapy and piracetam 4.8 g/d, especially when given during the first months after the stroke, or otherwise in combination with an intensive speech training. In both double-blind studies the piracetam treated group improved about 60% more than the group who only got speech therapy and placebo. All these data may be explained by the restorative or enhancing influence of nootropic drugs on neurotransmitter systems closely related to learning and memory functions. E.g. piracetam restores the availability and function of muscarinic and NMDA receptors in aging animals, most probably through a modulation of the psychico-chemical properties of the neuronal membrane such as the membrane fluidity. Most clinicians would recommend speech and language therapy (SLT) for aphasic patients. The question of when and for how long SLT should be administered still remains controversial. The aim of this trial is to evaluate the efficacy of early SLT in patients with acute stroke and aphasia in a randomized controlled trial. This report will present design and methods and discuss feasibility.
                Consecutive patients with first ever ischemic stroke and aphasia are assessed by the Amsterdam-Nijmegen Everyday Language Test (ANELT) and a short version of the Norsk Grunntest for Afasi. The treatment is language enrichment therapy, and the therapy is given 45 min/day for 15 weekdays. The primary outcome is the difference in the degree of aphasia between the SLT treated group and the control group measured by ANELT at 3 weeks.
                Around 10% of acute consecutive patients with aphasia are included. Of the first 79 included patients, 86% have completed the study according to protocol. We intend to include 125 patients, which provide sufficient statistical power to detect a clinically significant difference in the degree of aphasia.
                It is feasible to conduct a randomized controlled study on very early SLT for acute aphasic patients. A number of studies suggest that drugs which increase the release of norepinephrine promote recovery when administered late (days to weeks) after brain injury in animals. A small number of clinical studies have investigated the effects of the noradrenergic agonist dextroamphetamine in patients recovering from motor deficits following stroke. To determine whether these findings extend to communication deficits subsequent to stroke, we administered dextroamphetamine, paired with speech/language therapy, to patients with aphasia.
                In a prospective, double-blind study, 21 aphasic patients with an acute nonhemorrhagic infarction were randomly assigned to receive either 10 mg dextroamphetamine or a placebo. Patients were entered between days 16 and 45 after onset and were treated on a 3-day/4-day schedule for 10 sessions. Thirty minutes after drug/placebo administration, subjects received a 1-hour session of speech/language therapy. The Porch Index of Communicative Ability was used at baseline, at 1 week off the drug, and at 6 months after onset as the dependent language measure.
                Although there were no differences between the drug and placebo groups before treatment (P=0.807), by 1 week after the 10 drug treatments ended there was a significant difference in gain scores between the groups (P=0.0153), with the greater gain in the dextroamphetamine group. The difference was still significant when corrected for initial aphasia severity and age. At the 6-month follow-up, the difference in gain scores between the groups had increased; however, the difference was not significant (P=0.0482) after correction for multiple comparisons.
                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. To examine whether the amount of speech and language therapy influences the recovery from poststroke aphasia.
                A hospital stroke unit and community.
                A prospective, randomized controlled trial.
                Aphasic stroke patients were randomly allocated to receive 5 hours (intensive therapy group, n=51) or 2 hours (standard therapy group) of speech and language therapy per week for 12 consecutive weeks starting as soon as practicable after the stroke. Another 19 patients were recruited for 2 hours per week of therapy and were treated by National Health Service (NHS) staff (NHS group). OUTCOME MEASURE AND ASSESSMENT: The Western Aphasia Battery. Assessments were made blind to randomization at baseline and 4, 8, 12 and 24 weeks after the start of therapy. Data were analysed by intention to treat.
                The mean (SD) Western Aphasia Battery score at week 12 for the intensive, standard and NHS groups was 70.3 (26.9), 66.2 (26.2) and 58.1 (33.7), respectively. There was no treatment effect of intensive therapy (P > 0.05), but there was a statistically significant difference between the standard study and the NHS groups (P = 0.002 at week 12 and 0.01 at week 24).
                Intensive speech and language therapy (as delivered in this study) did not improve the language impairment significantly more than the ;standard' therapy which averaged 1.6 hours/week. The improvement in aphasia was least in patients who were in the NHS group. These patients received 0.57 (0.49) hours of therapy per week. Preclinical research suggests that piracetam (a nootropic drug) may improve cognitive functions, but previous studies have failed to demonstrate a clear benefit for the treatment of Alzheimer's disease (AD). We report a 1-year, double-blind, placebo-controlled, parallel-group study with a high dose of piracetam (8 g/d per os) in 33 ambulant patients with early probable AD. Thirty subjects completed the 1-year study. No improvement occurred in either group, but our results support the hypothesis that long-term administration of high doses of piracetam might slow the progression of cognitive deterioration in patients with AD. The most significant differences concerned the recall of pictures series and recent incident and remote memory. The drug was well-tolerated.
Drug treatment with piracetam may be effective in the treatment of aphasia after stroke. Further research is needed to explore the effects of drugs for aphasia, in particular piracetam. The safety of the drug should be of primary interest. Researchers should examine the long-term effects and whether it is more effective than speech and language therapy.