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DO CHOLINESTERASE INHIBITORS WORK?
  1. Hugh Rickards

Abstract

Acetylcholinesterase inhibitors (ACHEI) are used for a range of brain disorders, particularly dementia. I reviewed the available literature to find an answer to the question of their effectiveness and efficacy based on the question “if a patient were sitting in front of me with this disorder, how best could I inform the discussion about whether or not to prescribe these medications”. The evidence from schizophrenia is that they have no effect. The evidence from Parkinson disease and related Lewy body disorders suggests a mild beneficial effect on cognition of doubtful clinical significance with a higher chance of adverse events. This was better in the purer Parkinson and dementia (PDD) group. There was a similar, but less marked, cognitive benefit in vascular cognitive impairment. Trials in MCI showed a trend to benefit but no difference in “conversion to dementia” rate. In Alzheimer dementia the evidence was strongest and showed a mean difference between treatment and placebo of 1.4 points on the MMSE with no effect on behaviour. The DOMINO trial showed, surprisingly, that patients on ACHEI were less likely to withdraw from treatment than those on placebo. Although patients in this trial taking ACHEI did better in cognition and function than those who weren't, all the groups deteriorated to some extent. The CALM-AD study showed that ACHEI did not affect behaviour in a group of patients who had BPSD. Finally, a recent meta-analysis calculated the probability of a randomly chosen patient with dementia achieving significant benefit on treatment when compared to placebo (with 1.0 being “certain of benefit” and 0.0 being “certain of no benefit”). For ACHEI in AD the probability of cognitive benefit was 0.58 and for global functioning 0.55. The probability of harm, leading to withdrawal was 0.56. In summary, “probability of benefit” was roughly equal to “probability of harm”. However, patients and carers may have specific viewpoints on these probabilities in terms of their own values and these should be discussed.

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