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No evidence for efficacy and safety of indomethacin for treatment of mild to moderate Alzheimer's disease

Extensive evidence implicates inflammatory processes in the pathogenesis of Alzheimer's disease. Non-steroidal anti-inflammatory drugs such as indomethacin have been proposed for the treatment of patients with Alzheimer's disease. Only one study met criteria for inclusion. In this one selected trial, authors did not carry out statistical analyses on the absolute change from baseline, but on the percentage change from the baseline score. Taking into account the difficulties in evaluating a single trial, at present there is no indication for treatment of mild to moderate Alzheimer's disease with indomethacin.

Wprowadzenie

Inflammatory processes involving cytokines, prostaglandins, free radicals and glial cells have been implicated in the pathogenesis of Alzheimer's disease. Non-steroidal anti-inflammatory drugs such as indomethacin attenuate inflammatory reactions. Hence, there may be a role for some of these drugs in the treatment of Alzheimer's disease.

Cele

To examine the efficacy of indomethacin in the treatment of patients suffering from Alzheimer's disease.

Metody wyszukiwania badań

The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (which contains records from many different medical and trials databases) on 14 April 2004 using the terms "indomethacin", "indome*" and "NSAIDS". In addition two independent reviewers systematically searched relevant computerized databases and Internet sites. This was supplemented by hand searching and additional references sought from selected papers.

Kryteria doboru badań

Single or multi-centre placebo-controlled randomized trials examining the efficacy of indomethacin in patients diagnosed with Alzheimer's disease were eligible for selection for this review. Using a standard extraction form, inclusion/exclusion criteria were set to ensure design quality and lack of bias of all trials included.

Zbieranie i analiza danych

Data were collected independently by two reviewers and any discrepancies were subject to discussion. Corresponding authors were contacted for any missing data needed for statistical analysis.

Główne wyniki

Only one study was selected for this review (Rogers 1993). We detected no statistically significant difference between indomethacin treatment and placebo for the individual cognitive tests: Mini Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale ( ADAS), Boston Naming Test (BNT) and Token Test (TK). Dropouts and death rate were the only reported results that were amenable to evaluation. The dropout rate was higher in the indomethacin group (10/24) than in the control group (6/20). Gastrointestinal adverse events were more prevalent in the treatment group (5/24 compared with 1/20 in control group). There was no statistically significant difference in death rate between the two groups (p=0.9).

Wnioski autorów

On the basis of this one trial and subsequent analysis of data as reported by the authors, indomethacin cannot be recommended for the treatment of mild to moderate severity Alzheimer's disease. At doses of 100-150 mg daily, serious side effects will limit its use.

Cytowanie
Tabet N, Feldman H. Indomethacin for Alzheimer's disease. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD003673. DOI: 10.1002/14651858.CD003673.

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