Interaction between psychological and pharmacological treatment in cognitive impairment. A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Long-term and high-dose piracetam treatment of Alzheimer's disease. Effectiveness of speech therapy for aphasic stroke patients. A randomised controlled trial. Efficacy of early cognitive-linguistic treatment and communicative treatment in aphasia after stroke: a randomised controlled trial (RATS-2).
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. 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. 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. Aphasic stroke patients were randomly allocated to either a speech therapy group receiving treatment twice a week for 24 weeks or a no-treatment control group. Patients in both groups improved and there were no significant differences in language recovery between the 104 patients allocated to the treatment group and the 87 allocated to the no-treatment group. This treatment regimen, which is representative of clinical practice, is ineffective for most aphasic stroke patients. The two main approaches in aphasia treatment are cognitive-linguistic treatment (CLT), aimed at restoring the linguistic levels affected, semantics, phonology or syntax, and communicative treatment, aimed at optimising information transfer by training compensatory strategies and use of residual language skills. The hypothesis that CLT is more effective than communicative treatment in the early stages after stroke was tested in this study.
                In this multicentre, randomised, parallel group trial with blinded outcome assessment, 80 patients with aphasia after stroke were included within 3 weeks post-stroke. Patients received 6 months of CLT, comprising semantic and/or phonological training, or communicative treatment for at least 2 h per week. They were assessed before treatment and at 3 and 6 months with the Amsterdam-Nijmegen Everyday Language Test (ANELT-A, primary outcome) and semantic and phonological tests (secondary outcomes). The intervention effect was evaluated by means of analysis of covariance, with adjustment for baseline scores.
                There was no difference between the mean ANELT-A score of the CLT group (n=38) and the communicative treatment group (n=42), at 3 months (adjusted difference 1.5, 95% CI -2.6 to 5.6) or at 6 months (adjusted difference 1.6, 95% CI -2.3 to 5.6) post-stroke. On two of six specific semantic and phonological tests, the mean scores differed significantly, both in favour of CLT.
                This study does not confirm the hypothesis that patients with aphasia after stroke benefit more from CLT, aimed at activation of the underlying semantic and phonologic processes, than from general, non-specific communicative treatment (ISRCTN67723958 Current Controlled Trials).
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.