EDITOR, - As two of the authors of a paper that reports the efficacy and safety of 160 mg of tacrine (base) used over 30 weeks,1 we believe that the conclusions of Maltby et al2 are inappropriate with regard to the use of tacrine for the treatment of Alzheimer's disease for the following reasons.

Firstly, the number of patients treated with tacrine who completed the entire 36 weeks of treatment was exceedingly low (14 patients). It is surprising that the authors are willing to make such negative comments about the drug, given the results of our study and another recently published, well controlled, multicentre study,³ the combined results of which are based on over 500 patients who completed the protocols.

Secondly, the maximum dose of tacrine used in Maltby et al's study was 100 mg (hydrochloride salt, equivalent to 80 mg base), with an average dose of 77.3 mg. The efficacy of tacrine begins to become apparent at these dosage levels, and the benefit of the drug is greater at doses of 120 and 160 mg (base). As opposed to the contention of the authors, a dose of 160 mg of tacrine is well tolerated by many patients, and it is safe.

Thirdly, in Maltby et al's study, the group treated with tacrine had an average duration of illness of 5.4 years, and the placebo group had an average duration of illness of 2.5 years. One would expect the viability of the brain's intrinsic cholinergic system to become increasingly compromised as Alzheimer's disease progresses, and therefore the response to tacrine to become less. Thus, to compare a tacrine group with a placebo group that has a duration of illness of less than half is inappropriate.

Fourthly, the liver dysfunction observed by the authors during the course of …