The three cholinesterase inhibitors — donepezil, rivas-tigmine and galantamine — are currently all recommended for use in patients with Alzheimer’s disease. New NICE guidance will be finalised next month.
What is the evidence?
Evidence from randomised controlled trials (RCT) has shown that these drugs have beneficial effects on cognitive and global outcome measures.
However, a recent systematic review of 22 RCTs has shown that the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer’s is questionable (BMJ 2005; 331: 321).
Although the outcomes measuring cognition did show beneficial effects of cholines-terase inhibitors, these effects were minimal. The review found that the methodological quality of the available trials was poor.
The results of an RCT that compared both donepezil and vitamin E against placebo were deeply disappointing (N Engl J Med 2005; 352: 2379). Although an initial benefit of donepezil was seen during the first year, it was not sustained.
One study has shown that patients with dementia are now being referred earlier to specialists, which has led to more cholinesterase inhibitors being prescribed (Psychiatric Bulletin 2006; 30: 131).
Some experts believe memory clinics have spent time and money monitoring patients on cholinesterase inhibitors rather than actually ensuring the delivery of multidisciplinary care plans (BMJ 2006; 333: 491).
Various meta-analyses have shown quite consistently that these medicines have modest beneficial effects compared with placebo (Cochrane Database Syst Rev 2006; (1): CD001190, and Health Technol Assess 2006; 10: 1).
Implications for practice
When NICE adjusted costs to take account of the benefits attributed to these drugs it estimated that donepezil, rivastigmine, and galantamine had a cost per quality-adjusted life year gained of £48,000, £32,000, and £38,000 respectively.
Draft NICE guidance issued in January 2006 recommends that cholinesterase inhibitors should be considered in the treatment of patients with moderately severe disease but not for those patients who have milder symptoms.
If the proposed recommendations by NICE are adopted, the NHS would save £15 million in the first year, £45 million in the second, and more than £60 million in the third.
NICE has rejected appeals against initial guidance. The final guidance will be issued next month.
www.nice.org.uk — NICE
www.Alzheimers.org.uk — Alzheimer’s Society
Dr Louise Newson is a GP in the West Midlands and author of ‘Hot Topics for MRCGP and General Practitioners’, Pas Test 2006
Dementia is very common.
Cholinesterase inhibitors may be less effective than initially thought.
NICE guidelines may change in the near future.
The appropriate use of cholinesterase inhibitors in Alzheimer’s disease is controversial.