A DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF TACRINE FOR ALZHEIMERS-DISEASE

The present study was designed to determine whether oral tacrine (tetr ahydroaminoacridine, THA) improves the symptoms of patients with mild to moderate Alzheimer's disease. The study was a multicentre, randomiz ed double-blind, placebo controlled, parallel group study with individ ual 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 b y NINCDS-ADRDA workgroup classification and a Mini-Mental State Examin ation score of 10 or more. Most patients were titrated to 80 mg of tac rine per day. Tacrine improved patients in clinicians' global ratings and the relatives' global rating compared to placebo (p < 0.05). Tacri ne did not significantly improve the Mini-Mental State Examination sco re, although as with other scores the trend favoured tacrine. There wa s a substantial variation in response among patients. Twelve patients in the tacrine and four in the placebo group were withdrawn from the s tudy due to raised LFTs or adverse events. No serious sequelae resulte d from these. One patient in the placebo group and two in the tacrine group died from causes which were considered unrelated to the treatmen t.