Long-term effects of tacrine in alzheimer's disease: An open study

To study the efficacy and safety of prolonged tacrine administration, we monitored 41 patients meeting NINCDS–ADRDA criteria for probable Alzheimer's disease while taking tacrine on an open basis for a period of up to 192 weeks. Dependent variables were the Abbreviated Mental Test Score (AMTS) and aspartate transaminase levels (AST) as a measure of liver function which was tested every 2 weeks at first and at less frequent intervals thereafter, the 10‐week measure being taken as an index of long‐term liver function. Survival analysis revealed that the median time for the AMTS score to decline from its level at the open label baseline to at least one point below on two successive occasions was 91.5 weeks (range 20–190 weeks). Fifteen patients showed liver function abnormalities during tacrine administration but these abnormalities resolved following reduction of the dose in all but two patients. We conclude that tacrine may temporarily delay the progression of symptoms of Alzheimer's disease and that administration of this drug can safely be prolonged with appropriate clinical supervision. These results may help to guide the clinical use of tacrine now that this drug has been licensed in some countries and is under consideration in others.