A double-blind, placebo controlled, multicentre study of tacrine for alzheimer's disease

The present study was designed to determine whether oral tacrine (tetrahydraminoacridine, THA) improves the symptoms of patients with mild to moderate Alzheimer's disease. The study was a multicentre, randomized double-blind, placebo controlled, parallel group study with individual determination of maximum tolerated dose over a period of 12 weeks. One hundred and fifty-four patients (93 women) aged 44–92 years (mean 75) were selected as having probable Alzheimer's disease as defined by NINCDS–ADRDA workgroup classification and a Mini-Mental State Examination score of 10 or more. Most patients were titrated to 80 mg of tacrine per day. Tacrine improved patients in clinicians‘ global ratings and the relatives’ global rating compared to placebo (p < 0.05). Tacrine did not significantly improve the Mini-Mental State Examination score, although as with other scores the trend favoured tacrine. There was a substantial variation in response among patients. Twelve patients in the tacrine and four in the placebo group were withdrawn from the study due to raised LFTs or adverse events. No serious sequelae resulted from these. One patient in the placebo group and two in the tacrine group died from causes which were considered unrelated to the treatment.