Cochrane reviews – in their own words

Rivastigmine for Alzheimer's disease
Jacquleine Birks
Centre for Statistics in Medicine, University of Oxford , Oxford , UK

“Alzheimer's Disease is associated with the loss of neurons in the brain. Drugs that might enhance the action of the remaining neurons may help to slow the impairment that follows. Rivastigmine is an acetylcholinesterase inhibitor, a type of drug that might do this.

Although the acetylcholinesterase inhibitors appear to have a beneficial effect, there have been concerns about their costs. For example, in the UK, it costs £1300 a year to treat a patient with rivastigmine. This has limited their use and the National Institute for Health and Clinical Excellence (NICE), the agency that reviews drugs and treatments for the National Health Service in the UK, has recommended that they should be restricted to people with moderate disease.

In the earlier versions of our Cochrane review of rivastigmine for mild to moderate Alzheimer's Disease, we showed that doses of 6 mg to 12 mg per day of rivastigmine improved the rate of decline of cognitive function and a person's ability to do activities of daily living (1). However, acetylcholinesterase inhibitors are often accompanied with adverse events typically gastrointestinal problems such as nausea, vomiting, diarrhoea, abdominal pain and lack of appetite, as well as dizziness, fainting and weakness.

It is important, therefore, to know if smaller, more frequent doses of rivastigmine might reduce the incidence of adverse events, while keeping the beneficial effects. A new study, which included nearly 2000 patients, set out to do this and we are able to include the results of this trial in the updated review (2). It tested the safety and effectiveness of two strengths of a rivastigmine skin patch: a 10 cm2 patch, this is about a quarter of the size of a credit card, delivering 9.6 mg/day and a patch twice the size, which delivers 17.4 mg/day. I was really interested in how these would perform against each other and what we found is that there doesn't seem to be any difference in efficacy; but the larger, higher dose patch is associated with more adverse events.

Patients using the larger patch scored similarly on cognitive function tests to those using the smaller patch. But, 66% of patients with the larger patch had at least one adverse event, compared to only 51% of patients with the smaller one. For example, about 19 in every 100 patients with the larger patch experienced vomiting, compared to about 6 per 100 with the smaller patch. Gastrointestinal adverse events in general were less common with the smaller patch. Patients using the smaller patch also had lower rates of adverse events when compared to patients who took a 6 mg to 12 mg daily dose of rivastigmine capsules.

Our updated Cochrane reviews seem to show that the smaller patch is an improved method for administering rivastigmine. It has the same efficacy, but a better adverse event profile, compared with the larger patch or capsules.”