Ginkgo extract or cholinesterase inhibitors in patients with dementia: what clinical trials and guidelines fail to consider.

Dementia of Alzheimer's type (DAT), together with vascular dementia, is the most important indication for Ginkgo biloba extract (EGb). The therapeutic efficacy of this extract is founded on neuroprotective, metabolic and rheological effects. In addition to these mechanisms--which also form the basis of the activity of the older synthetic nootropics--the hypothesis that DAT is due to a "cholinergic deficit" at central synapses has led, over the last decade, to the development of a new group of drugs for this indication, the cholinesterase (ChE) inhibitors. Thus nowadays, EGb is competing, on the synthetic side, with the ChE inhibitors tacrine, donepezil, rivastigmine and galantamine. No direct comparative trials have been undertaken, but long-term studies lasting 24-56 weeks to demonstrate efficacy have been carried out with both groups of substances in accordance with current EU guidelines. To date, only one psychometric scale has gained general acceptance as the primary criterion of efficacy, namely the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), whose scores range from 0 to 70 (the lower the better). The initial scores of patients in the trials were between 20 and 30; the improvements after 6 months treatment (less those seen with placebo) were about 2 points under Ginkgo extract and 2 to 4 points with the ChE inhibitors. However, the relatively small differences are called into question by the occurrence of drug-specific side effects with the ChE inhibitors. Unlike the treatment with EGb, up to 90% of the patients given the ChE inhibitors developed nausea and vomiting, so there is a suspicion that methodological reasons in the sense of an "unblinding" of the treatment groups caused the apparent superiority in the intensity of the effect. In addition, the benefits of treatment were rapidly reversed after ending administration of ChE inhibitors, which did not occur to the same extent with EGb. Adverse drug reactions are more than 10 times more common with the ChE inhibitors and the treatment costs about five times higher than with EGb. Given the limited therapeutic options for DAT, treatment with EGb still appears to be the method of choice compared to the ChE inhibitors.