Gabe Allen recently posted Do Certain Medications Like Benadryl Boost the Risk of Dementia? | Discover Magazine about how medications like Benadryl (diphenhydramine) can “boost the risk of dementia.”1 As Allen reports, there is a large body of evidence over the past 20 years indicating that medications with anticholinergic effects impact dementia. There are over 140 ingredients with anticholinergic properties! I say ingredients, because many medications (Rx and OTC) have multiple ingredients. For example, sleep agents (including the so-called OTC “PM” pain relievers), cold medications and others contain at least one anticholinergic agent. Students of pharmacology learn to connect the word “dry” with anticholinergics. That is, side effects are dry mouth, urinary retention, and drowsiness. Allen points out that labels list these side effects. But anticholinergics also contribute to the risk of cognitive impairment and falls.
When the FDA held hearings in 1984 on whether Benadryl should go over the counter, I was one of many who provided testimony against the move. Benadryl was approved for OTC in 1985 and now there are at least 16 other OTC ingredients with anticholinergic properties.
Some anticholinergic ingredients have mild side effects, some moderate and some strong anticholinergic effects. I co-chaired a measure group for the Pharmacy Quality Alliance (PQA) to develop a quality measure, PolyPharmacy, Use of Multiple Anti-Cholinergic Agents regarding older adults prescribed two or more strong anticholinergics.2 Boustiani and others3 first identified these agents as particularly problematic. They were incorporated into the famous “Beers Criteria” (Named after Dr. Mark H. Beers who first published a list of prescription medications that are potentially inappropriate in older adults.)4 The PQA multiple anticholinergic measure is now part of the CMS “STARS” program as a display measure and will move to a full STARS measure in 2026.5
Over the years, it has become clear that it is the total anticholinergic burden that is concerning. (3) For example, two Rx medications with a high score of 3 each are no worse than 3 Rx medications each with a low score of 1 along with a strong OTC anticholinergic such as diphenhydramine. We report a case study of an individual with a high anticholinergic burden from 5 RX and 2 OTC medications with anticholinergic effects!6
ActualMeds has a robust set of medication risk rules including the entire set of Beers 2023 rules, PQA measures, and CMS STARS measures. And now, ActualMeds has introduced its InConcert Anticholinergic Burden Calculator showing the Rx and OTC medications taken by a patient along with each individual contribution to the burden score. The ActualMeds InConcert medication system alerts the pharmacist around these medications and enables them to quickly initiate an action plan for the prescribers.
Health plans partnering with ActualMeds now have a rapid mechanism to identify and characterize the totality of anticholinergic effects and associated risks. Action plans facilitate remediation of risks with a goal of mitigating the contribution of anticholinergic medications to cognitive impairment.