Clinical studies with galanthamine

The use of galanthamine in Alzheimer's disease dates back to 1986. A small-scale open pilot study was conducted with 9 patients at the psychiatric clinic in Gugging, Austria, in the following year. Two other pilot studies, performed in Austria and Great Britain, showed mixed results that could be explained by weaknesses of their designs; however, these were sufficient to arouse attention. In a subsequent multicenter, placebo-controlled study, 167 Alzheimer patients entered a 3-week single-blind, dose-titration phase, with an upper limit of 50 mg galanthamine per day. The 141 drug responders were randomized either to continue galanthamine therapy, or to receive placebo for the following 10-week double-blind phase. At endpoint, those who had remained on galanthamine had improved by an additional 1.66 ADAS-Cog points, while those switched to placebo had deteriorated by 1.40 points. Several other studies, some still ongoing, and data from Austria where galanthamine has been licensed for mild to moderately severe Alzheimer's disease, confirm that the optimal dose range is between 30 and 45 mg/day, that side effects are mild and transient, and do not include hepatotoxicity. After 3 years of continuous therapy, a group of outpatients who received galanthamine in addition to other drug treatment still showed cognitive benefit relative to a control group. Therefore, galanthamine should be regarded as an excellent representative of the emerging second-generation acetylcholinesterase inhibitors.