Piracetam for dementia or cognitive impairment (Cochrane Review)

A substantive amendment to this systematic review was last made on 19 February 2001. Cochrane reviews are regularly checked and updated if necessary.

Background: Piracetam is a drug which may exert an action in enhancing memory and other intellectual functions through mechanisms which are ill-understood and still debated. At low dosage, piracetam can produce cognitive enhancement perhaps by increasing oxygen and glucose utilisation via ATP pathways. At higher dosage, it is associated with platelet anti-aggregation and rheological effects with antithrombotic properties (Moriau 1993). Central and peripheral microcirculation is also enhanced by the promoting of red blood cell deformability and by reducing adherence of damaged red blood cells to endothelial cells. The usefulness of piracetam in patients with Alzheimer's disease and vascular dementia and unspecified dementia is still controversial with mixed results, particularly from small clinical trials, but results from larger scale trials have been more encouraging.In spite of the uncertainties about its efficacy in dementia, either unclassified or according to the major subtypes of dementia (vascular, Alzheimer's disease or mixed vascular and Alzheimer's disease), piracetam is currently a frequently prescribed drug for cognitive impairment and dementia in several continental European countries.

Objectives: To determine the clinical efficacy of piracetam for the features of dementia or cognitive impairment, classified according to the major subtypes of dementia: vascular, Alzheimer's disease or mixed vascular and Alzheimer's disease, or unclassified dementia, or cognitive impairment not fulfilling the criteria for dementia.

Search strategy: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 November 2000 using the term spiracetam, nootropic and 2-Oxo-1-pyrrolidine.In addition the pharmaceutical company responsible for marketing most of the piracetam worldwide, UCB Pharma, provided a comprehensive list of abstracts, which included many unpublished studies. As many of these unpublished, placebo-controlled studies will be reviewed as possible.

Selection criteria: All unconfounded trials specified as randomized in which treatment with piracetam was administered for more than a day and compared with placebo in patients with dementia of Alzheimer type, vascular dementia,or mixed vascular and Alzheimer's disease, or unclassified dementia, or cognitive impairment not fulfilling the criteria for dementia.

Data collection and analysis: Data were extracted independently by two reviewers. Each study was independently verified as fulfilling the inclusion criteria. Studies were rated for methodological quality by assessment of blinding and loss before analysis as described by Jadad et al. (1996). Studies were pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat analyses were undertaken. Sensitivity analyses were performed to determine if successive elimination of those studies performing most poorly on these quality criteria changed the effect estimate.

Main results: Unfortunately, many of the studies were of cross-over design and first-phase data were unavailable, or could not be extracted. Global Impression of Change was the only outcoeme for which there was a significant volume of evidence from the pooled data. There was evidence of heterogeneity in the results from the individual studies, chi-square test = 20.8 (df=5). Using a fixed effects model the odds ratio for improvement in the piracetam group compared with the placebo group was 3.55, [95% CI][2.45, 5.16]. If a random effects model was used the odds ratio was 3.47 [1.29, 9.30]. If one single-blind study was excluded, the fixed effects model yielded an odds ratio of 3.36 [2.29, 4.99] and if a random effects model was applied then the odds ratio was 2.89 [1.01, 8.24]. The evidence of effects on cognition and other measures, was inconclusive.

Reviewers' conclusions: At this stage the evidence available from the published literature 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.There is a need for further evaluation of piracetam by :1) Obtaining the data from the identified studies for an individual patient database review,2) Performing a randomized trial of piracetam in patients with diagnoses made by currently accepted diagnostic criteria. The trial should extend over for a period of at least 6 months and preferably longer. Specific cognitive instruments which are sensitive to change, Clinician Global Impression of Change, levels of dependency and caregiver quality of life scales should also be incorporated in such a study.

Citation: Flicker L, Grimley Evans J.. Piracetam for dementia or cognitive impairment (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.

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This is an abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).

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