Since then, three other drugs have come onto the market, all of which attempt to do the same trick of increasing acetylcholine in the brain. As expected, these drugs are all deadly rivals. Pfizer's Aricept (donepezil), has an advertising tagline that says 'when Alzheimer's hits home, Aricept can help'; Novartis' Exelon (rivastigmine) claims to be 'another step forward against Alzheimer's disease'; and Shire Pharmaceuticals/Janssen's Reminyl (galantamine) sells itself with the somewhat vague tagline 'Reminyl is now'.
So far, Pfizer is the only manufacturer to have threatened a lawsuit against the recent NICE ruling that none of these drugs is really worth taking in the early stages of AD. Will the drugmaker win their case? Our prediction is no-and, frankly, because the evidence is stacked against them.
The only large-scale, truly independent clinical trial of Pfizer's Aricept was carried out by a team of British researchers at the University of Birmingham. In a double-blind trial that lasted for more than two years, Aricept was tested head-to-head against a placebo in over 500 patients who had mild-to-moderate AD.
The study's conclusions? Aricept works, but its benefits are very small-"below minimally relevant thresholds" (Lancet, 2004; 363: 2105-15). As study director Professor Richard Grey stated in the report: "Patients and their families would probably notice no difference if the drug was stopped."
What's more, even clinical trials funded by the drug companies them-selves failed to show much benefit with any of their products. For example, Oxford University researchers recently scrutinized data from 24 separate Pfizer-sponsored Aricept trials, involving more than 5000 patients at different stages of AD, and concluded that "the treatment effects are small and are not always apparent in practice". Add to that the strong likelihood of "many adverse events" such as nausea, vomiting, diarrhoea, muscle cramps, dizziness, fatigue and anorexia, and it's little wonder that there's what the researchers politely refer to as a "debate" over whether Aricept is worth a candle (Cochrane Database Syst Rev, 2006; 1: CD001190).
The same Oxford scientists have also examined another of Pfizer's claims-which is also supported by the strictly independent Alzheimer's Society-that Aricept helps prevent the onset of AD, stopping what is classified as 'mild cognitive impairment' (MCI) from turning into full-blown Alz-heimer's. The researchers' conclusion? According to their report: "There is no evidence to support the use of Aricept for patients with MCI. The putative benefits are minor, short-lived and associated with significant side effects" (Cochrane Database Syst Rev, 2006; 3: CD006104).
What of Aricept's two other rivals, however? Again, independent studies of the clinical data have exposed the drug companies' marketing hype.
With MCI, for example, Polish researchers concluded earlier this year that the efficacy of all three cholinesterase-blocking drugs was "questionable", especially given the high incidence of side-effects, some of which-as in the case of Reminyl-apparently can be fatal (Neurol Neurochir Pol, 2007; 41: 13-21).
As for full-blown AD itself, three groups of independent researchers all agree that the three drugs, although having slightly different modes of action, all produce broadly similar effects-or rather, a lack of effects. Their benefit to Alzheimer patients is variously described as "not large" (Cochrane Database Syst Rev, 2006; 1: CD005593), "limited" (Tijdschr Psychiatr, 2006; 48: 17-26) and "small" (Drugs Aging, 2007; 24: 155-67).