Cholinesterase inhibitors can slightly delay the deterioration of cognitive function

Donepezil, galantamine, and rivastigmine, the 3 cholinesterase inhibitors (ChEIs) approved in Germany for the treatment of mild-to-moderate Alzheimer's disease, can slightly delay the deterioration of cognitive function in affected patients. This is the result of a final report published by IQWiG on the Internet on 10 April 2007.

The report is part of a comprehensive project commissioned to IQWiG by the German Federal Joint Committee, which comprises the assessment of drug and non-drug interventions in patients with dementia. In this context, the Institute concludes that ChEIs can delay the onset of certain symptoms in patients with Alzheimer's disease.

In the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), which assesses cognitive function and memory on a scale ranging from 1 to 70, patients who took a ChEI for at least 4 months achieved on average a 3-point higher score than patients who took a placebo. In the ChEI arms, an absolute percentage of about 15% more patients achieved at least 4 more points than patients in the placebo arms.

There were also indications that ChEIs delay the loss of the ability to cope with daily activities.

However, a benefit of ChEIs was not demonstrated regarding health-related quality of life and prevention of placement in a nursing home. Overall, the sound studies currently available only allow assessments to be made for a period of up to 6 months of treatment.

Considerable adverse effects in some patients

All 3 drugs triggered adverse effects, which were considerable in some patients, in a dose-dependent manner (e.g. diarrhoea, nausea, and vomiting).

Benefit of ChEIs is controversial

Cholinesterase inhibitors in the treatment of Alzheimer's disease are currently being discussed controversially on a national and international level. Several scientific assessments on ChEIs are currently available; however, in part, the underlying methodology varies. In Great Britain in particular, the assessment by the National Institute for Health and Clinical Excellence (NICE) is currently being debated. A first assessment of these antidementia drugs in January 2001 led to a positive result. However, a second assessment in March 2005 led to a negative result, and subsequently ChEIs are no longer reimbursed by the National Health Service (NHS).

In a revised version of November 2006, the restricted use in moderate disease is recommended under certain conditions, but not for patients in early or late stages of disease.

Due to this restricted recommendation, NICE - for the first time in its history - is facing legal challenges by a manufacturer.

Different assessment criteria

The IQWiG report contradicts the NICE report only at first sight. NICE reached its recommendation after employing a cost-benefit model, and weighing these factors against each other. According to this, ChEIs are not recommended, or only recommended with certain restrictions, as their cost is too high compared with their relatively small benefit. In contrast, IQWiG assessed only the patient-relevant benefit. Cost assessment was not part of the commission.

IQWiG also assesses treatment alternatives in dementia

Cholinesterase inhibitors are drugs that delay the degradation of the neurotransmitter acetylcholine; consequently, greater amounts of this transmitter are available for the processing of information in the brain. A further aspect of IQWiG's commission on dementia deals with the drug memantine. Products containing ginkgo are also being assessed; the publication of the corresponding final report is planned for this summer. In addition, IQWiG is evaluating non-drug interventions.

Procedure of report production

On 8 September 2006, IQWiG presented the preliminary report for discussion. A total of 17 substantial comments were submitted on these preliminary results. Unclear aspects of these comments were discussed with the authors in a scientific debate on 14 November 2006 in Cologne. Topics addressed included the clinical relevance of the effects detected, as well as the study duration required by IQWiG. The preliminary report was subsequently revised. The meeting minutes of the scientific debate, as well as the written comments, are included in the appendices of the final report.

On 20 August 2009 the Federal Joint Committee commissioned an update search on this final report: "Cholinesterase inhibitors in the treatment of Alzheimer's disease