Oral Tetrahydroaminoacridine in Long-Term Treatment of Senile Dementia, Alzheimer Type

TLDR

Further observations are needed to clarify the role of THA in Alzheimer’s disease. The study employed a three‑phase design: an initial open‑label treatment, a double‑blind placebo‑controlled crossover, and a long‑term open‑label phase with oral THA. THA produced significant cognitive improvements versus baseline and placebo, with sustained benefits over 12.6 months and no serious adverse events, indicating potential temporary palliative benefit in Alzheimer’s patients. Published in N Engl J Med 1986; 315:1241–5.

Abstract

We treated 17 patients who had moderate to severe Alzheimer's disease with oral tetrahydroaminoacridine (THA), a centrally active anticholinesterase, in a three-phase study. In the nonblinded first phase of the study, significant improvement occurred in subjects who received the drug, as compared with their pretreatment status, on the global assessment (P = 0.001), the Orientation Test (P = 0.001), and the more sophisticated Names Learning Test (P = 0.001). During the second phase, the subjects served as their own controls in a double-blind, placebo-controlled, cross-over study in which the order of administration of the drug and placebo was randomly assigned. Among the 14 subjects completing Phase II, THA treatment produced significantly better results than placebo on the global assessment (P = 0.003), the Orientation Test (P = 0.004), the Alzheimer's Deficit Scale (P = 0.003), and the Names Learning Test (P = 0.001). Twelve subjects have entered Phase III, which involves long-term administration of oral THA. The average duration of treatment in these subjects at present is 12.6 months; symptomatic improvements have occurred, and no serious side effects attributable to THA have been observed. These encouraging initial results suggest that THA may be at least temporarily useful in the long-term palliative treatment of patients with Alzheimer's disease. We stress that further observations will be required before a clear assessment of the role of this agent can be made. (N Engl J Med 1986; 315:1241–5.)