BACKGROUND: Tacrine is one of the first drugs to be widely marketed for the loss 
of memory and intellectual decline in Alzheimer's disease. The alleged success 
of tacrine in the treatment of these symptoms has been heralded as confirmation 
of the cholinergic theory of Alzheimer's disease. However, the efficacy of 
tacrine for symptoms of dementia remains controversial. This is reflected by the 
low rate of prescription of tacrine in countries where it is approved and the 
lack of approval by several regulatory authorities in Europe and elsewhere. The 
uncertainty about the efficacy of tacrine is due to the difficulties in 
interpretation of the results from the clinical trials. The reasons for this are 
the small effects of tacrine compared to placebo for all outcomes; the high 
incidence of adverse events; the lack of benefit observed in several trials; the 
use of cross-over designs and their associated methodological problems in a 
disease like dementia; the use of different measurement scales to assess outcome 
in different trials; and the problem of high dropout rates.
OBJECTIVES: To determine the clinical efficacy of tacrine for the symptoms of 
Alzheimer's disease.
SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was 
searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the 
Group's search strategy for full details).
SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which 
treatment with tacrine was administered for more than a day and compared to 
placebo in patients with dementia of the Alzheimer's type.
DATA COLLECTION AND ANALYSIS: Data were extracted independently by two 
reviewers, 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 data were used.
MAIN RESULTS: This review produced no clear results. The results were compatible 
with tacrine producing improvement, no change or even harm for those with 
Alzheimer's disease. It was not possible to use many of the published results in 
a combined analysis. For measures of overall clinical improvement, the 
intention-to-treat analyses failed to detect any difference between tacrine and 
placebo (OR 0.87; 95%CI 0.61 - 1.23). Behavioural disturbance, as measured by 
the Alzheimer's Disease Assessment Scale-noncognitive, failed to detect any 
difference between tacrine and placebo (SMD -0.04; 95%CI -0.52 - 0.43). For 
cognition function, the effect of tacrine was not statistically significantly 
different from placebo for the MiniMental State Examination score (0-30; high 
=good) (SMD 0.14; 95%CI -0.02 - 0.30) and was barely statistically significantly 
in favour of treatment for the Alzheimer's Disease Assessment Scale-cognitive 
scale (SMD -0.22; 95%CI -0.32 - -0.13). Adverse events were not reported in a 
systematic way in the different trials, making formal comparison difficult. 
Raised serum liver enzymes was the major reason for withdrawal. The odds ratio 
for withdrawal due to an adverse event was significantly different from one, the 
control group experienced fewer events (OR 5.7; 95%CI 4.1-7.9). Gastrointestinal 
side effects (diarrhoea, anorexia, dyspepsia and abdominal pain) were the other 
major cause of adverse events and for withdrawal, and the odds ratio for 
withdrawal was also significantly different from one in favour of the control 
group (OR 3.8; 95%CI 2.8-5.1). No deaths were reported in any of the studies 
during the trial period, up to six months.
REVIEWER'S CONCLUSIONS: This review provides no convincing evidence that tacrine 
is a useful treatment for the symptoms of Alzheimer's disease. However, as so 
few trials presented data in a format suitable for pooling, the results of this 
review may be modified when further data from all relevant trials are included. 
There is an urgent need for the independent evaluation of the data already 
existing in the trials but not accessible through published or grouped data. A