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Anticholinergic drugs: some questions and answers

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A small group of researchers from Primary Care and from Psychiatry & Applied Psychology, led by Professor Carol Coupland, has been addressing the question of whether receiving medications with anticholinergic properties is a possible risk factor for subsequently developing dementia. This is an important question as there are a lot of medications that have anticholinergic properties and they are used to treat a variety of conditions from depression to incontinence, also including gastrointestinal problems and asthma. There had been some other studies previously but not all with the same findings. Our group was able to use data from a very large general practice database that provides information about drugs prescribed and diagnoses, so it was possible to look at whether people who had received anticholinergic drugs were more likely to develop dementia at a point in the future.

Our findings, reported in the prestigious journal JAMA Internal Medicine this week, were that indeed the risk did seem to be increased and this was increased by higher doses and longer periods of exposure. However, although this suggests that anticholinergic drugs may contribute to causing dementia, it is far from proving it. Even though we took several statistical precautions, it is still possible that something called reverse causality or protopathic bias might occur – that is, the prescription of the drug might result from rather than cause the process leading eventually to the dementia.

These findings have implications for the large numbers of people who may be taking anticholinergic drugs, so it’s really important for us to get our message across clearly so that patients are not thrown into panic. We were on the BBC News and in several UK and US papers so there is a level of interest in the study. In short though, don’t panic and stop all your drugs but discuss it with your doctor.

I received this email and I have agreed with its author that we can include it in Dementia Day to Day, so I am most grateful for this permission. I have changed some details.



I was very interested to read your study today looking at the relationship between anticholinergic drug exposure and the risk of dementia.

Earlier in life, I became depressed and was prescribed a drug called Seroxat [paroxetine]. When I tried to stop taking this sometime later, I had severe withdrawal symptoms, despite very slow and extended titration of doses under medical supervision. (My Drs acknowledged that this was an issue with withdrawal rather than a reoccurrence of the original illness.) As a result I was switched to Prozac and then clomipramine but unfortunately I still experienced withdrawal problems. This has led to me being on a dose of around 25mg of clomipramine for 15 years.

I am concerned about the possible resulting impact on my memory and would be grateful if you are able to direct me towards any further reading.



Thank you for your enquiry. Obviously you probably want to discuss your situation with your doctor. A couple of comments though. My experience is that Seroxat (paroxetine) is one of the more likely antidepressants to give problems on its withdrawal. Both Seroxat and clomipramine (though not Prozac) were in the list of drugs that we included as having significant anticholinergic properties.

The degree of risk we observed was related to both the duration of taking the drugs and also to the dose (we calculated a measure called total cumulative anticholinergic drug exposure as our main exposure variable). We mainly looked at the period between 1 and 11 years before the diagnosis of dementia, since in the year prior to diagnosis it would be difficult to tell what was cause and effect. However, we also looked as far back as 20 years before diagnosis and there still seemed to be a comparable level of risk.

Apart from the fact that you are on a low dose of clomipramine, this information is probably not very reassuring. However, it also important to consider that we are talking about a level of risk here, which is far from a certainty that an individual will develop dementia. Indeed, more than half of the controls in our study (i.e. people without a diagnosis of dementia) had been prescribed anticholinergic drugs too. The other factor to consider is obviously that it isn't good to have depression either, so continuing with effective treatment if it is needed seems like a good idea, just that it needs to be balanced against future risk. Only you and your doctor can decide how this looks in your case.

As for further reading, the paper itself is open access (https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2736353and contains references to all the other important papers that have been published. I imagine that material written for the public may need to be revised as a result of our findings though.



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