What we can learn from open-label extensions of randomized clinical trials.
Arch Neurol. 2006 Jan;63(1):18-9.
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The results of our study suggest that long-term (up to a year) use of memantine has sustained effects. We are encouraged that a high percentage of those completing the double-blind study enrolled in the open-label extension (97 percent), and that a high percentage of those who enrolled completed the open-label study (78 percent). This adds confidence to the observations that rates of change slowed down for subjects who switched from placebo to memantine, and remained slower than expected for subjects originally randomized to memantine.
Our study cannot answer the question of what happens after the first year on treatment. As in all open-label extension studies, there is gradual attrition during the open-label period, and the patients who remain in the study until the end are not formally followed after the extension period is over. In my clinical experience, moderate to severe patients maintained on a cholinesterase inhibitor and memantine seem to decline more slowly and retain more function for an extended period of time, often many years. Ethical issues related to long-term randomization of AD patients to placebo groups for longer than 6 months or so prohibit designing studies that would provide a definitive answer regarding how long the treatments should be maintained. In clinical practice, I would raise the issue of discontinuing treatment with a family if I did not see any cognitive or functional ability that we would like to retain. Practically, this is increasingly rare as AD patients who now live into very late stages of disease often succumb to another condition despite retained abilities and continued antidementia treatment.
Regarding your second point, memantine was used in Germany for many years before it began a formal development program in dementia, somewhat analogous to the use of hydergine in the U.S. and elsewhere in the world. The formal studies of memantine, performed according to draft regulatory guidelines which were not produced until the 1990s, resulted in the demonstration of efficacy in well-defined populations, and the approval of the drug here and in Europe.
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