“Hayfever pill to fight Alzheimer’s” is the headline in The Sun . The newspaper suggests that dimebon – a hayfever pill –“combats memory loss in patients with the brain disease”.
The story is based on a study in 183 Russian patients with mild-to-moderate Alzheimer’s disease. This study was small and limited to a particular setting and culture, but it highlights the potential of dimebon (previously used as an antihistamine and unlicensed in the UK) in the treatment of mild-to-moderate Alzheimer’s disease. Larger studies are likely to follow to test how well this drug might work in other countries and with other forms of the disease. Such research will be welcome for a disease with few effective treatments.
Where did the story come from?
Dr Rachelle Doody and colleagues from Baylor College of Medicine in Texas, the Russian Academy of Medical Sciences, Mount Sinai School of Medicine in New York and other medical and academic institutes across Russia and the USA, carried out this study. Several of the investigators declared a conflict of interest as they were associated in some way with the company Medivation, which manufactures the drug and funded the study. The study was published in the peer-reviewed medical journal: The Lancet .
What kind of scientific study was this?
This was a double-blind randomised controlled trial that included 183 people with mild-to-moderate Alzheimer’s disease. Patients were aged over 50 years and were recruited from 11 sites across Russia. Brain images (through MRI or CT) taken within 12 months of enrolment were available for each patient. Patients were allowed to take other medication alongside the study treatment, but they were excluded if they had taken other treatments for Alzheimer’s disease, such as cholinesterase inhibitors or N-methyl-D-aspartate receptor antagonists (amantidine), in the 60 days before the study. People whose dementia was not caused by Alzheimer’s disease were also excluded.
Patients were randomly allocated to receive daily dimebon or placebo for 26 weeks. The researchers then assessed cognitive function with a number of different measures, but their main one was a questionnaire called the ADAS-cog which assesses memory, language and coordination. Assessments were undertaken before the study (at baseline), halfway through treatment (at 12 weeks) and at the end of treatment (26 weeks). The researchers then compared the change in cognitive function over time between the groups to determine the effect of dimebon compared with placebo. The researchers also collected information on adverse events.
Some patients were enrolled in an extension of this study (up to 52 weeks). Of the 155 patients completing the 26-week phase, 134 of them agreed to this extension, and assessments were available for 120 of these at 52 weeks.
What were the results of the study?
By the end of the study, patients taking dimebon had improved by about two points on the scale used to assess cognitive symptoms of Alzheimer’s (ADAS-cog), while those taking placebo worsened by about two points. There was a statistically significant benefit of dimebon on this outcome. A similar pattern of improvement with dimebon and worsening with placebo was seen with the other measures of cognitive function.
At 52 weeks, dimebon was still significantly better than placebo on all measures and, with some measures, the effect relative to placebo increased over time. At 26 weeks, self-reported (i.e. not clinically diagnosed) symptoms of depression were greater with dimebon than placebo (though these symptoms did not lead to study discontinuation and were not reflected in a measure of depression that was included as part of the study). Other effects (including insomnia, atrial flutter and muscle pain) occurred more frequently with dimebon, but overall rates were low and the researchers say that “the clinical significance of this is unclear”. Overall, there was no difference between groups in the number of people who experienced at least one adverse event, and at week 52 there appeared to be more serious adverse events in the placebo group than in the dimebon group.
What interpretations did the researchers draw from these results?
The researchers conclude that their study has shown that people with mild-to-moderate Alzheimer’s improve when given dimebon compared with baseline and compared with people taking placebo. They suggest that the 52-week results demonstrate a continued and increasing improvement in symptoms. They conclude that the safety profile of the drug is similar to that seen with currently licensed treatments for Alzheimer’s.
What does the NHS Knowledge Service make of this study?
This randomised controlled trial is the best evidence to date of the effects of dimebon for treating cognitive symptoms in people with Alzheimer’s disease.
- The study had sound methods and applied international standards for carrying out research. Although it took place across 11 different sites in Russia (which might mean important differences in the way the study was carried out), the researchers have made an effort to ensure that the study was robust and reliable (each site followed international guidelines for high-quality research). Researchers and participants were unaware of the treatment they were receiving. This blinding is important in reducing bias in a study.
- The research demonstrates a significant improvement in overall cognition in Russian patients with mild-to-moderate disease. The researchers note that studies will be needed to confirm the results in other populations and settings. They say that their Russian sample was on average younger than people usually included in Alzheimer’s studies, and that they may have been less likely to be taking other medications alongside their study treatments.
- It is unclear precisely what clinical benefit the two-point improvement on the ADAS-cog represents. Given that the total score on this scale is 70 points, this may represent a small improvement in real-life terms.
In summary, this study – while small and limited to a particular setting and culture – highlights the potential of dimebon (previously used as an antihistamine) in the treatment of mild-to-moderate Alzheimer’s disease. Larger studies are likely in the future.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
Daily Mail, 18 July 2008
The Sun, 18 July 2008
The Guardian, 18 July 2008
The Daily Telegraph, 18 July 2008
BBC News, 18 July 2008
Links to the science
Lancet 2008; 372:207-215