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. An independent meta-analysis of the individual-patient data is required. The results and conclusions of this update are unaltered by further searching as the additional studies do not add any further valid/eligible data.