OBJECTIVE: To see whether combined treatment with oral tacrine 
(tetrahydroaminoacridine; THA) and lecithin improves the symptoms of patients 
with Alzheimer's disease.
DESIGN: Multicentre double blind, placebo controlled, random order crossover 
trial with individual determination of maximum tolerated dosage and four month 
follow up.
SETTING: Outpatient departments at six university neurological centres.
PATIENTS: 67 Outpatients (24 men, 43 women) aged 53-81 (mean 66 (SD 7.3)) 
selected according to the following criteria: probable Alzheimer's disease as 
defined by the National Institute of Neurological and Communicative Disorders 
and Stroke and the Alzheimer's Disease and Related Disorders Association; 
absence of mood disorder; mini mental state score lower than 26; availability of 
a close relative able to complete questionnaires; and informed consent of the 
patient or his or her closest relative, or both.
INTERVENTIONS: Mean of 114 mg tacrine or placebo daily plus 1200 mg lecithin 
daily given in three divided doses for one four week active treatment period and 
one four week control period without washout at crossover.
MAIN OUTCOME MEASURES: Cognitive state as assessed by Folstein's mini mental 
state rating scale, behavioural state as assessed by the Stockton geriatric 
rating scale, and overall state as assessed with a visual analogue scale rated 
by both the relative and the physician.
RESULTS: Compared with placebo tacrine did not improve either the mini mental 
state score (mean 14.9 (SD 7.3) v 14.8 (7.3)) or the Stockton geriatric score 
(28.2 (15.7) v 28.7 (17.8)), but a slight and statistically significant 
improvement occurred in the physician's score on the visual analogue scale (6.3 
(10.2) v 11.6 (17.9)). Seven patients dropped out. Six patients were excluded 
because of acute hepatitis and one withdrew for personal reasons not related to 
treatment. Two other patients developed acute hepatitis at the end of the eight 
week crossover trial and another during the follow up study. Twenty patients 
complained of gastrointestinal side effects.
CONCLUSIONS: Neither short term nor long term treatment with oral tacrine at 
dosages lower than 125 mg/day improves the symptoms of Alzheimer's disease. 
Moreover, these dosages may induce hepatitis (nine of 67 patients in this 
series).