Anticholinergic drugs have been used for a variety of medical conditions for a very long time, but recent studies have drawn this class of medicine under scrutiny for unanticipated side effects.

The Anticholinergic Effect

An observational study published a few years ago, showed that the use of “medicine with definite anticholinergic effects” was associated with greater decline in the Mini Mental State Examination (MMSE) scores, indicating possible cognitive impairment. The study also pointed to a possible increase in mortality as well(1). However, there were contradictory findings also on this topic, which further baffled the medical community(2).

Earlier last year, scientists from University of Washington, Seattle published a similar study in JAMA Internal Medicine that provided the "strongest evidence yet" to associate the use of anticholinergic medicines with cognitive decline(3). The study team included commonly used drugs such as antihistamines and cough medicines that were widely available in pharmacies and clinics.

“We found an obvious dose-response relationship between anticholinergic drug use, and risk of developing dementia: the higher the usage, the greater the risk”, commented study lead scientist, Dr. Shelly Gray, PharmD(4).

The Research Method

The study team recruited over 3,400 participants who were 65 years or older, and who did not suffer from pre-existing dementia at the time of study enrolment. The patients were followed up every two years or until death occurred, and results were adjusted for demographic characteristics, health behaviours and baseline health status(3). This adjustment was conducted to filter the effects of these confounding factors.

In order to accurately calculate the exposure to anticholinergic medicines, and to standardize such effects across different types of drugs, the scientists adopted a previously published method of standardized conversion of different anticholinergic doses into a single exposure parameter. This allowed the scientists to correctly and consistently measure the “anticholinergic burden” of the study population. In addition, the study also defined “anticholinergic” as medicines that exhibit strong anticholinergic activity in accordance to a panel of experts.

Findings from Research

The result of the study reaffirmed the findings from previous trials. Over follow-up periods, 797 study subjects developed dementia (23.2%), and among these subjects 637 (79.9%) were shown to develop possible or probable Alzheimer's disease. A cumulative dose-response relationship was observed for both dementia and Alzheimer's disease too. The increased risks for both diseases were most severe for those who consumed the highest amount of anticholinergics.

In order to translate the study findings into actionable information, Dr. Gray provided a layman’s explanation “…that taking the minimum daily effective dose of one of the anticholinergic agents every day for 3 years would put people in the highest risk category”. In addition, she also mentioned that people could end up in this highest category by even taking these medications at minimum effective daily doses intermittently over a period of time, or by taking higher dosages over a shorter period of time(4).

While the study discovered an association between the abovementioned variables, it does not prove that anticholinergics definitively cause dementia, but rather simply showed that the two were linked. Another important factor to consider is that the study population was restricted to 65 years and above; there was no data to support the same findings among a younger population.

It is understandable that the results raised concerns within the medical community. In particular, the study’s authors urged healthcare professionals especially family doctors to be more cautious when they prescribe these medicines. Alternatives should be considered if the perceived risks outweigh the benefits. MIMS

References:
1. Fox C, Richardson K, Maidment ID, Savva GM, Matthews F, Smithard D, et al. Anticholinergic Medication Use and Cognitive Impairment in the Older Population: The Medical Research Council Cognitive Function and Ageing Study. J Am Geriatr Soc. 2011;59(8):1477–83.
2. Fox C, Livingston G, Maidment ID, Coulton S, Smithard DG, Boustani M, et al. The impact of anticholinergic burden in Alzheimer’s dementia-the laser-AD study. Age Ageing. 2011;40(6):730–5.
3. Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative Use of Strong Anticholinergic Medications and Incident Dementia Shelly. JAMA Intern Med. 2015;175(3):401–7.
4. Hughes S. “Strongest Evidence Yet” Links Anticholinergic Drugs, Dementia [Internet]. Medscape Pharmacist. 2015 [cited 2016 May 11]. Available from: http://www.medscape.com/viewarticle/838788#vp_1


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