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. [The effect of piracetam on involuntary movements in Huntington's disease. A double-blind, placebo-controlled study]. Piracetam in elderly motorists. Piracetam in alcoholic organic mental disorder: a placebo controlled study comparing two dosages. On the efficacy of piracetam in geriatric patients with acute cerebral ischemia: a clinically controlled double-blind study. Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study. [Effect of piracetam on the brain-organic psychosyndrome in cerebrovascular insufficiency. Results of a double-blind study in 40 cases]. Moclobemide in elderly patients with cognitive decline and depression: an international double-blind, placebo-controlled trial. Effects of donepezil adjunctive treatment to ziprasidone on cognitive deficits in schizophrenia: a double-blind, placebo-controlled study.
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. Piracetam and its derivatives, a group of "nootropic" drugs thought to act as metabolic enhancers in the brain, have been widely used to treat a variety of cognitive disorders. Two studies have reported that this compound reduces the severity of involuntary movements in acute onset hemichorea. We therefore randomly assigned 11 patients with Huntington's disease to receive high doses of intravenous piracetam (12 g in 250 ml of saline) or placebo on different days. A blinded observer then rated the severity of involuntary movements over a period of 4 hours. Significant aggravation (p < 0.05) of chorea was seen in patients taking piracetam, in comparison with ratings for both baseline and placebo, 4 hours after administration but not during earlier assessments. Although the mechanism causing this effect is unidentified, we believe that our findings indicate that piracetam should not be used to treat the cognitive disorders accompanying Huntington's disease. 101 elderly motorists with reduced reaction capacity were examined under real traffic conditions with regard to their driving ability. They were given a daily dose of 4.8 g piracetam or placebo over a six-week period in a randomised double-blind study. The percentage of correctly solved sign-observance items, which reflects orientation and perception in real traffic conditions, increased in the placebo-treated test-group from 79.86% in the pretest to 80.07% in the retest, whereas the test subjects of the piracetam-treated group improved their performance from 77.08% to 84.16%. After being treated with piracetam for 6 weeks, the drivers showed a significantly better performance than the placebo-group. Of particular interest is the finding that the test-subjects who had scored less than 80% in the pretest improved without exception in the retest after treatment with piracetam. The following paper presents an investigation of the efficacy of piracetam in alcoholic organic mental disorder. A double-blind placebo-controlled study design was used to compare 2 dosages of the substance (2 X 3 g vs. 2 X 12 g). Cognitive function was assessed on days 0, 7, 14, 28, 42. Analysis of the results from 24 patients showed a clear-cut amelioration of cognitive functions in all 3 treatment groups. No difference could be demonstrated between the administration of placebo and the lower dose of piracetam. Patients on the higher dose showed an earlier improvement on one of the tests, but the final scores were similar in all three treatment groups. Using a randomized, double blind group comparison, the efficacy and tolerance of piracetam as an additional therapy of hydroxyethyl starch, venous infusion and low dose heparin treatment, which are the basis of therapy in our hospital, has been studied in patients displaying acute cerebral ischemia. A total of 56 patients were enrolled, of whom 27 were given piracetam and 29 served as a control during a 28-day period. Using single photon emission computer tomography (SPECT) analysis, we observed that in 23 piracetam-treated patients (85.2%) a reduction in the area of brain regions displaying an impaired flow rate occurred (P < 0.001; Fisher's exact two-sided test). Only six of placebo-treated patients (20.7%) showed an improved flow rate. Analysis of the recorded computer tomography map gave an improvement coefficient >2 (flow rate marginally or better improved) for 23 piracetam patients as compared with 5 placebo patients (P < 0.001, Uleman test). Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation.
                The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure.
                The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003).
                Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated.
                ClinicalTrials.gov identifier NCT00190008. nan The new reversible MAOl moclobemide was compared with placebo in the treatment of elderly patients with DSM-III diagnosis of dementia and/or of major depression.
                Six hundred and ninety-four elderly patients with symptoms of depression and cognitive decline entered an international, multi-centre, double blind trial in which they were randomly allocated to treatment with either moclobemide 400 mg daily or placebo for 42 days. Five hundred and eleven patients met DSM-III criteria for dementia and were also depressed (DEM+D); 183 did not meet DSM-III criteria for dementia but met the criteria for DSM-III major depressive episode and also suffered from cognitive decline (MDE+CD).
                Analysis of the 17 and 24-item Hamilton Depression Scale scores showed that moclobemide, compared with placebo, produced significantly greater improvement in both the demented and depressed groups (P = 0.001 both diagnostic groups). There was an improvement in cognitive function as measured by the SCAG Factor 1 in moclobemide treated patients (P = 0.005 DEM+D; P = 0.02 MDE+CD). There was no evidence of decline in cognitive function as the result of treatment. Clinical global assessment of tolerance was 'excellent' and 'good' in 88% of the moclobemide and in 92% of the placebo treated patients. The proportion of patients discontinuing treatment prematurely was similar in both treatment groups. There were no significant differences in side-effects between treatment groups. There were no significant changes in vital signs, ECG or laboratory findings in either treatment group. There were no dietary restrictions and no report of any tyramine reaction.
                Moclobemide was shown to be a safe, well tolerated and effective antidepressant, which did not cause impairment of cognitive function in elderly patients with a DSM-III diagnosis of dementia and/or DSM-III major depression. The objective of this study was to examine the effects of adjunctive treatment with the acetylcholinesterase inhibitor, donepezil, on cognitive deficits and psychopathology in schizophrenic patients treated with the antipsychotic, ziprasidone. The design of the study was double blind, placebo controlled, and longitudinal. Patients were treated with ziprasidone for 8 weeks, thereafter randomized to 4 months of double-blind adjunctive treatment with either donepezil (dose, 5-10 mg) or placebo. The severity of psychopathology (PANSS) and the cognitive deficits were examined at baseline and after 4 months. A total of 21 schizophrenic patients were enrolled, of whom 11 patients completed the trial (donepezil, n = 7; placebo, n = 4). There were no within- or between-group differences in changes on the Positive and Negative Syndrome Scale scores or a global cognitive score. Within-group improvements (all at trend level P = 0.07) were seen in the placebo group on Trail-Making Test B, immediate verbal recall, and set-shifting errors. The donepezil group showed a significant deterioration on planning efficiency (P = 0.04). Between-group differences were found between the lack of improvement in immediate verbal recall in the donepezil group and the improvement in the placebo group (P = 0.02), and between the deterioration of planning efficiency in the donepezil group and the stability in the placebo group (trend level, P = 0.07). Linear regression analyses showed that neither baseline psychopathology scores, baseline levels of cognitive deficits, nor psychopathology changes over time accounted for these changes in cognitive scores. The study found no evidence of improved cognition after treatment with donepezil, although the conclusions that can be drawn are limited by the small sample size.
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.