Long-term and high-dose piracetam treatment of Alzheimer's disease. Piracetam in elderly psychiatric patients with mild diffuse cerebral impairment. Piracetam in chronic brain failure. A controlled trial of piracetam in intellectually impaired patients with Parkinson's disease. Interaction between psychological and pharmacological treatment in cognitive impairment. [The significance of quantified EEG in Alzheimer's disease. Changes induced by piracetam]. Drug therapy and memory training programs: a double-blind randomized trial of general practice patients with age-associated memory impairment. Piracetam-induced improvement of mental performance. A controlled study on normally aging individuals. Haemorheological pattern in initial mental deterioration: results of a long-term study using piracetam and pentoxifylline.
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. In a 12-week double-blind study, piracetam at two dose levels (2.4 and 4.8 g/day) was compared to placebo in the treatment of 60 elderly psychiatric patients with mild diffuse cerebral impairment, but no signs of focal brain lesion. The psychiatric illness, schizophrenia or affective disorder, of patients selected was in remission at the time of the study. Monthly evaluations by the nurse revealed that piracetam improved overall functioning, particularly alertness, socialization, and cooperation, relative to the control group. Patients treated with 2.4 g/day piracetam also showed significant improvement in scores for the full IQ and the memory quotient on the Wechsler Adult Intelligence and Memory Scales; greater response was seen in those with lower initial scores. Piracetam at 4.8 g/day had a more rapid onset of action on behavioral variables than 2.4 g/day, but its therapeutic effect tended to diminish at 12 weeks, possibly as the result of overstimulation. Piracetam did not appear to interfere with concomitant psychotropic maintenance medication or affect the psychiatric illness itself. A double-blind, placebo-controlled trial was carried out on 109 aged patients with minimal or with moderate chronic brain failure to assess the effectiveness of piracetam (2.4 g per day) in preventing the progression of dementia. Patients received piracetam or placebo each for 6 weeks, the order of treatment being at random. The results of 19 psychological tests, repeated at 6-weekly intervals, showed that piracetam produced statistically significant improvement in only one of them and then only during the first 6 weeks of treatment. These findings, therefore, do not support the usefulness of piracetam in the treatment of such patients. Twenty patients with Parkinson's disease and marked intellectual impairment or dementia participated in a double-blind placebo controlled trial of the nootropic, piracetam. A standardized neurological examination, a neuropsychological test battery, and a functional scale, The Sickness Impact Profile, were completed for all patients. They were then assigned by blind randomization to drug or placebo conditions receiving 3.2 g of piracetam or an identical amount of placebo for 12 weeks. The dose was increased to 4.8 g for an additional 12 weeks. Neurological, psychological, and functional measures were rated as improved, unchanged, or worsened in comparison to baseline performance. Twenty-five percent of the patients did not complete the trial for reasons unrelated to the medication. Although there was a significant improvement on one subtest of the functional scale, no significant effects were demonstrated in cognitive or neurological measures. 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. One study was performed in 12 patients with presenile Alzheimer's disease (group I), the other one in 16 patients with mild senile dementia of Alzheimer type (group II). In each study, patients were divided into two randomized parallel groups, one receiving placebo, the other piracetam (9 g daily in group I piracetam and 2.4 g daily in group II piracetam) during three months, piracetam induced a decrease in EEG power on the 2-6 Hz range (group I piracetam), 3-5 Hz and 7 Hz (group II piracetam) and an increase of EEG power in the 9-11 Hz range (group I piracetam) and in the 10 Hz and 13 Hz frequencies (group II piracetam). There was also a significant improvement in the Trail Making Test part A in group II piracetam. Correlations between decreased EEG low frequency components and improvement in some psychometric tests were found significant in the two groups. It seems that the main effect of piracetam was to induce increased alertness. The same results were found in both studies; the good reproducibility suggests that EEG spectral analysis is a reliable tool in the assessment of psychotropic drug effects. A double-blind randomized trial was performed involving 162 patients with age-associated memory impairment (AAMI) selected and followed by their general practitioners. Two intervention methods--a drug and a cognitive therapy--were assessed in combination. Three randomized parallel groups of 54 patients each, aged 55 years and over, were followed and treated for 3 months. After a placebo wash-out period of 10 days, one group received 2.4 g of piracetam, another group, 4.8g, and the third, a placebo. A total of 135 patients, 45 in each group, completed the study. Combined therapy was most effective in patients whose baseline performance on memory tests was lowest. The best results were observed with 4.8 g of piracetam, especially when training sessions began after 6 weeks of drug treatment. This result was confirmed by the global impression of the principal investigator. A double-blind, intra-individual cross-over comparison of the mental performance of 18 aging, non-deteriorated individuals during two 4-week periods of piracetam (1-acetamide-2-pyrrolidone) and placebo administration was performed using conventional and computerized perceptual-motor tasks. In a majority of these tasks the subjects did significantly better when on piracetam than on placebo, a finding consistent with ratings completed by two independent observers. The findings indicate new avenues for the treatment of individuals with reduced mental performance possibly related to disturbed alertness--a neglected group of psychiatric conditions. A group of 80 elderly subjects affected with recent onset (less than 6 mth) slight to moderate mental deterioration was observed before and after oral drug treatment for a period of 28 wk. The study consisted of four randomized groups of subjects homogeneous for age, sex and life habits. The first group received a placebo, the second group received piracetam (1600 mg 3 times a day), the third group received pentoxifylline (400 mg 3 times a day), and the fourth group received a combination of piracetam and pentoxifylline. At the beginning and end of each phase of the study, neuropsychological and haemorheological parameters were evaluated in all subjects. The results show that the most evident improvement in psycho-intellectual performance, associated with an increase of whole blood filtration values, was obtained in the group treated with the two-drug combination.
Published evidence does not support the use of piracetam in the treatment of people with dementia or cognitive impairment. Although effects were found on global impression of change, no benefit was shown by any of the more specific measures of cognitive function.
The evidence indicates a need for further evaluation of piracetam.