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TACRINE IMPROVES FUNCTION IN ALZHEIMER'S PATIENTS.

Tacrine, a centrally active acetylcholinesterase inhibitor, was recently approved for treating Alzheimer's disease. These two studies strengthen our knowledge of the drug's efficacy and safety.

The first study, a randomized, controlled, parallel-group trial, compared tacrine dosages up to 160 mg/day with placebo in 653 Alzheimer's patients at 33 U.S. centers. A total of 384 patients (59%) withdrew from the 30-week study; 74 percent because of adverse events. The primary reasons for withdrawal of tacrine-treated patients were asymptomatic liver transaminase elevations and gastrointestinal complaints.

Despite the high dropout rate, tacrine-treated patients had significant dose-related improvements on three different measures of function. One instrument documented improvement in 42 percent of evaluable patients in the tacrine group versus 18 percent of the placebo group. Patients taking the highest dose were most likely to show improvement.

The second study analyzed liver function in almost 2500 patients enrolled in five multicenter clinical trials. About half the patients had abnormal serum alanine aminotransferase levels and 25 percent had levels that were over three times the upper limit of normal. Most abnormalities occurred in the first 12 weeks, and 88 percent of patients who were rechallenged were able to resume long- term therapy. There were no deaths related to hepatotoxicity.

Comment: Tacrine is far from a cure for Alzheimer's disease; side effects are common and fewer than half the patients who could tolerate the drug improved. The fact that the first study enrolled more patients than originally intended due to extraordinary interest shows how desperately a treatment for Alzheimer's is needed.

— TH Lee

Published in Journal Watch General Medicine April 19, 1994

Citation(s):

Watkins PB et al. Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. JAMA 1994 Apr 6 271 992-998.

• Medline abstract (Free)

Knapp MJ et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. JAMA 1994 Apr 6 271 985-991.

• Medline abstract (Free)