he cause of Alzheimer's disease is unknown, but many of the symptoms have been related to changes in neurotransmitters, particularly acetylcholine. Tacrine (tetrahydroaminoacridine) has a central cholinesterase inhibitory action, in addition to other actions such as monoamine oxidase inhibition and potassium channel blockade. Reversal of some of the changes in patients with Alzheimer's disease has been reported in several small trials of tacrine. However, these findings have not been replicated consistently in large numbers of patients. To determine the efficacy and safety of treatment with tacrine plus lecithin in patients with mild to moderate Alzheimer's disease, Eagger and colleagues conducted a randomized, double-blind, placebo-controlled, crossover study.
The study included 89 patients who met criteria for probable Alzheimer's disease. Each patient underwent a comprehensive baseline assessment. The patients were assigned to receive either tacrine plus lecithin or placebo for 13 weeks. After a four-week washout period, the patients were crossed over to receive the other treatment. The dose of tacrine was determined by a standard protocol in which the dosage is gradually increased from 50 mg daily to 150 mg daily, if well tolerated. Lecithin was also given in a dosage of 10.8 g daily. Nineteen patients were excluded from the study because of side effects, four because of other illnesses and one because of noncompliance. Patients were evaluated every two weeks. The principal outcome measures were the Mini-Mental State Examination (MMSE) rating and the primary caregiver's rating of the Activities of Daily Living (ADL) scale.
Of the 65 patients who completed the study, 29 (45 percent) showed an improvement of three or more points in the MMSE score while receiving tacrine, compared with seven patients (11 percent) who showed improvement in the placebo group. Overall, MMSE scores improved significantly in the patients receiving tacrine. ADL scores were not affected by treatment with tacrine. Substantial variation was found among subjects in the response to treatment. The only patient characteristic that correlated with response was dysphasia. High dysphasia scores were associated with poor response to treatment.
Side effects occurred in 64 (72 percent) of the 89 patients who received tacrine and were severe in 11 (12 percent) of these patients. Side effects were predominantly gastrointestinal and appeared to be dose related. Liver enzyme levels rose in 46 percent of the patients receiving tacrine. The study findings show symptomatic improvement with tacrine equivalent to delaying the progression of disease for six to 12 months in patients with mild to moderate Alzheimer's disease. Further studies are needed to define the role of tacrine in the treatment of patients with Alzheimer's disease, particularly because of the high incidence of side effects and the potential for hepatotoxicity. (Lancet, April 27,1991, vol. 337, p. 989.)
COPYRIGHT 1991 American Academy of Family Physicians
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