Deleterious cognitive effects of antimuscarinic drugs

Editor, – I suggest that the article 'Anticholinergic drugs for overactive bladder' (Aust Prescr 2006;29:22-4) gives insufficient prominence to the inevitable occurrence of cognitive impairment from antimuscarinic drugs. There is overwhelming evidence that all antimuscarinic drugs cause cognitive impairment even in healthy people,¹ and this is frequently clinically significant in older people.^2,3,4 Any possibility that a treatment will worsen patients' mental function has profound implications and must be regarded with the utmost seriousness.

The therapeutic margin is narrow, or non-existent, and individual variations in blood concentrations and response mean that in practice it will be difficult to achieve a consistently favourable therapeutic effect. Many other commonly used drugs also have antimuscarinic effects so interactions are likely to be frequent. I suggest the average practitioner has insufficient knowledge of these interactions to successfully avoid them.⁵

Ken Gillman
Consultant psychiatrist
Pioneer Valley Private Hospital
North Mackay, Qld

Associate Professor KH Moore, one of the authors of the article, comments:

Dr Gillman makes an important point regarding the potential for anticholinergic drugs to induce or exacerbate cognitive impairment, especially in the elderly. However, he paints a rather black picture with very broad strokes so an examination of the evidence is needed.

Reference 1 describes a very precise psychometric analysis of scopolamine administration in 24 people, that showed significant decline in performance on spatial and pattern memory tests. This is hardly 'overwhelming evidence that all antimuscarinic drugs cause cognitive impairment'.

Similarly, references 2 and 3 describe studies with 30 and 16 users of a wide range of anticholinergic drugs. The first study showed a 19% attributable risk of mild cognitive impairment for these drugs. In the second paper, all patients were receiving the cholinesterase inhibitor donepezil for Alzheimer's disease. Not surprisingly, donepezil was less effective for preventing cognitive decline in those on anticholinergic drugs (at two years, but not at one year). Reference 4 is an interesting review article about the role of anticholinergic drugs in delirium but also discusses studies that included small numbers of patients (n = 15-34).

Reference 5 is a detailed review of the pharmacokinetics of a range of bladder-active anticholinergics. It is very informative but does not appear to support the suggestion that they should be avoided.

Nevertheless, our article could have made greater mention of the risks of anticholinergic therapy in exacerbating or precipitating cognitive impairment, especially in the elderly. These drugs should only be given in conjunction with bladder training at the lowest dose possible to achieve reduced frequency, urgency or urge incontinence, and for the shortest duration possible.