Dimebon For Dementia: Promising Clinical Trial Results

Editor's Choice
Main Category: Alzheimer's / Dementia
Also Included In: Clinical Trials / Drug Trials
Article Date: 21 Jul 2008 - 8:00 PDT

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A new study published in The Lancet has some promising results for treating Alzheimer's disease (AD) with the drug dimebon. Researchers show that in patients with mild-to-moderate AD, dimebon significantly improves the clinical course of the disease. Unlike any other approved AD therapy, dimebon resulted in increasing benefits over a 12 month period.

Dimebon has an interesting history, beginning in Russia where it was approved as an antihistamine designed to be taken orally. When other antihistamines entered the market, dimebon was removed for commercial reasons, and now it is not marketed anywhere. However, researchers maintained interest in the drug due to its ability to block the N-methyl-D-aspartate receptor signaling pathway and cholinesterase - neurological pathways that are important in neurodegenerative diseases. As interest in the pathway-blocking ability of dimebon subsided, researchers were able to show that the drug has neuroprotective effects in models for AD and Huntington's disease. This evolution of dimebon has led to this recent trial that was designed to analyze the safety, tolerability, and efficacy of dimebon for treating patients with mild-to-moderate AD

Dr. Rachelle S Doody (Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA) and colleagues conducted a randomized controlled trial consisting of 183 patients at 11 sites in Russia. The patients were all diagnosed with mild-to-moderate AD due to a score of 10 - 24 on the mini-mental state examination (MMSE). Randomization led to 89 patients in the group receiving dimebon 20mg three times a day and 94 patients in the group receiving placebo. The study forbade use of other antidementia drugs. Using the Alzheimer's disease cognitive assessment scale (ADAS-cog) and four other secondary measures, the researchers assessed the patients over a course of six months. Of the total, 155 (85%) patients completed the double-blind study - 78 (88%) in the dimebon group and 77 (82%) in the placebo group. For the following six months, 134 patients continued (and 120 finished) taking dimebon or placebo, and neither scientist nor patient knew which therapy the patient was receiving.

The main outcome measure was the ADAS-cog - a collection of questions that ask patients to track dates, understand instructions, follow commands, memorize words, and perform simple tasks such as copying drawings or addressing an envelope. Using the ASAS-cog, the researchers found that patients who received dimebon averaged about 4 points higher than patients who received placebo - a significant improvement for the dimebon group. In addition, dimebon patients improved by 1.9 points on the ADAS-cog compared to baseline and placebo patients demonstrated a significant decline. By the end of the trial, the difference between the two groups was 6.9 points on the ADAS-cog in favor of the dimebon group. Side-effects related to dimebon included dry mouth and depression, but the two groups saw about equal proportions of other adverse events.

"[Our] study of patients with mild-to-moderate Alzheimer's disease has shown that patients given dimebon were significantly improved compared with baseline, and compared with those taking placebo, for all five outcome measures. These outcome measures included assessment of cognition, function, and behaviour...The continued and increasing benefit of dimebon over the course of this study is especially important because at present no approved therapies for mild-to-moderate Alzheimer's disease have shown increasing improvement over 12 months," conclude the authors.

Professor Alistair Burns (Psychiatry Research Group, University of Manchester, UK) and Professor Robin Jacoby (Department of Psychiatry, University of Oxford, UK) write in an accompanying comment: "Addition of treatment options is good news for patients and clinicians-it promotes choice and offers the possibility of bespoke treatment packages which maximise the chances of response. Doody and colleagues' trial shows that dimebon is better than placebo-which is no mean feat considering the positive placebo responses in dementia. Further work will establish its efficacy (or otherwise) in addition to, or compared with, established treatments, and indeed a second phase III trial has recently been announced."

Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-tomoderate Alzheimer's disease: a randomised, doubleblind, placebo-controlled study
R S Doody et al.
The Lancet (2008). 372[9634]: pp. 207 - 215.
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Written by: Peter M Crosta
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