The paper reviewed here caused quite a sensation when it first came out and the reverberations are still being felt.This is the Dimebon study in mild-to-moderate Alzheimer’s Disease which took place in Russia. According to the Editorial in the same issue, in Russia there is a place for inpatient care with an emphasis on medication perhaps helping to explain the timing and location of this remarkable finding. The authors begin by referring to an open-label pilot study of Dimebon 20mg tds (over 8/52) providing sufficient evidence for the current study to take place.
In the current study, due to a limitation of resources the researchers focused on a single dosing schedule of 20mg tds in order to sufficiently power the study. This was a multicentre study (11 centres in Russia) including patients over the age of 50 with mild-to-moderate Alzheimer’s Disease (using DSM-IV and NIND criteria). MMSE scores were 10-24 and the Hachinski Ischaemic Score was less than or equal to 4. Written consent was obtained from participants and carers or legal guardians. The primary outcome measure was the ADAS-cog, with a number of secondary outcome measures including the MMSE, NPI for behaviour and ADCS Activities of Daily Living.
180 patients were recruited to the study. This was an intention-to-treat analysis with last observation carried forward. This was a randomised placebo controlled trial. The average age of participants was 68, all participants were white and 72% of patients were women (62% of controls), with an average of 12 years in education and 5 years of symptoms. The average MMSE was roughly 18.
89 people received Dimebon with 94 receiving placebo. In the Dimebon group 11 people discontinued, 5 of whom had adverse events. On the Dimebon arm of the trial, at week 26, there was an improvement on the ADAS-cog of 1.9 points compared to baseline and this was significant at the 0.001 level. The placebo group’s peformance decreased by an average of 2.1 points compared to baseline and this was significant at the 0.002 level. Interestingly the effect of Dimebon over Placebo was significant at the 0.0001 level!
There were similar trends in the MMSE, ADL measure and NPI with the Dimebon group increasing over baseline by 26 weeks and the Placebo group decreasing by this time. As an example, at 26 weeks the MMSE had increased by 1.8 points and the placebo group had decreased very slightly (0.5 points). There were some further results at 52 weeks, again with LOCF, showing that the placebo group continued to decline and also showing a slight dip in the Dimebon group scores. In the Dimebon group dry mouth was a common side effect (14% at 26 weeks) as was depressed mood (14% compared to placebo).
This is a very important study, showing that the drug Dimebon may be very important if further studies corroborate these findings. The MMSE scores in the Dimebon group were 18.7 at baseline and so even with an increase of 1.8 points there would still be impairment. Another feature of the results was the shape of the ADAS-cog improvement which showed a dip at 52 weeks. From the shape of the graph alone, the peak effect appeared to be at 39 weeks. However the study was best suited to looking at results at 26 weeks and so perhaps further studies might be able to look at those trends. Another finding was the increase in depressed mood in the Dimebon group over the placebo group and it would be interesting to see how treatment for depression impacted on scores.
The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.
Rachelle Doody, Svetlana Gavrilova, Mary Sano, Ronald Thomas, Paul Aisen, Sergey Bachurin, Lynn Seely, David Hung and ‘the dimebon investigators’. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomised, double-blind, placebo-controlled study. Lancet. Volume 372. Issue 9634. 19.7.8-25.7.8. pp207-215.