It still doesn’t. The wonder drug for Alzheimer’s disease has finally been put to the long-term test and shown to neither slow the onset of the disease nor delay taking the patient into care, according to a major double-blind, randomised UK trial of its effectiveness (Lancet, 2004; 363: 2105-15).

The study, funded by the National Health Service and run by the University of Birmingham, concluded that routine prescribing of the drug for dementia is a waste of NHS resources.

In this study, 565 patients with mild-to-moderate Alzheimer’s were given either donepezil or a placebo. At the end of five years, the patients given the drug showed only marginal (and non-significant) improvement in cognitive and functional ability, as measured by standardised tests - the MMSE (Mini-Mental State Examination) and BADLS (Bristol Activities of Daily Living Scales).

With the MMSE, those taking the drug scored less than one point better - of a possible 30 points - than those taking the placebo. On the BADLS, out of 60 possible points, those on the drug again did only one point better than those on placebo.

Donepezil is a cholinesterase inhibitor that slows the activity of acetylcholinesterase, which controls the breakdown of acetylcholine in the brain, a chemical considered vital for learning and memory. Patients with Alzheimer’s have been shown to have lower levels of acetylcholine. The theory is that, by slowing the process of chemical breakdown, donepezil will also slow the progress of the disease.

The drug was originally approved by the NHS National Institute for Clinical Excellence (NICE) for the treatment of Alzheimer’s after initial and subsequent studies showed promise (Rev Med Suisse Rom, 2003; 123: 471-4).

Besides not working very well, the drug‘s side-effects - agitation, aggressive behaviour, involuntary twitching and movement, even hallucinations - are strangely similar to those of the disease it is meant to treat, leaving you unsure whether Gran is getting worse or just experiencing a drug side-effect.

Other common or garden side-effects of donepezil include: diarrhoea, muscle cramp, nausea, fatigue, vomiting, insomnia, anorexia, headache, urinary incontinence and even accidents. Rarely, the drug can also cause seizures, gastrointestinal haemorrhage, gastric and intestinal ulcers, and liver dysfunction, including hepatitis.

But the biggest worry is its heart effects - including dizziness, sudden low blood pressure and syncope (abnormal heart rhythms). Drug manufacturer Pfizer admits to reports of syncope and seizures, with the possibility of a full heart block.

Nevertheless, such is medicine’s stalwart faith in drug therapy that, in three instances where patients developed abnormal heart rhythms, doctors fitted a pacemaker rather than take these patients off the drug (Europace, 2003; 5: 429-31).

Because of possible interactions, never take donepezil with: * succinylcholine-type drugs * NSAID (non-steroidal anti-inflammatory drug) painkillers * beta-blockers, for heart conditions * cholinergic or anticholinergic agents (such as antipsychotics) * paroxetine, an antidepressant * ketoconazole, an antifungal * erythromycin, an antibiotic.