If you opened your medicine cabinet right now, chances are you’d find an anticholinergic medication. These drugs have been around for decades and are used for a range of common conditions including allergies, depression, chronic pain, nausea, and more.
Growing evidence suggests long-term use of anticholinergic medications can be harmful to your brain health and may even raise your risk of dementia, says neurologist Glen R. Finney, MD, director of the Geisinger Memory and Cognition Program in Wilkes Barre, PA.
Finney sat down with WebMD to discuss exactly how anticholinergics affect your brain and what you can do to safely manage these medications.
WebMD: What conditions do anticholinergic medications typically treat?
Finney: There are two rough buckets where you would put anticholinergic medications. First, there are anticholinergic medications that we use for their anticholinergic effect. Second, there are medications that have other primary chemical functions but still have significant anticholinergic effects.
Of the first group, some of the classic ones have historically been used to treat tremor, like benztropine and trihexyphenidyl. Other powerful anticholinergic drugs, like scopolamine, have been used for nausea. A lot of the medications used for urinary incontinence are anticholinergic drugs. For example, oxybutynin and tolterodine.
For the second bucket, tricyclic antidepressants as a drug class are a big one. These are medications such as amitriptyline that were originally used as antidepressant medications, but people also use them for sleep and for pain. Some of the older antihistamines, like diphenhydramine and hydroxyzine, also have strong anticholinergic side effects. People use these, obviously, for severe allergy responses, but they're also used a lot for sleep and sometimes for anxiety.
WebMD: How do anticholinergic medications affect your brain function?
Finney: When anticholinergic drugs get into the brain, they block the neurotransmitter acetylcholine, which is essential for a huge amount of the brain's neurons to function.
Acetylcholine plays a central role in memory function. For short-term memory, acetylcholine helps you retain information in your working memory so you don’t forget. For your long-term memory, it enables you to organize and code important information. Acetylcholine is essential to those functions and other high level brain functions. Anticholinergics don’t interfere with all of it, but they interfere enough that you see decreased firing in those neurons.
WebMD: What are some cognitive effects from using these medications? How long do these effects usually last?
Finney: We have seen emerging evidence that anticholinergics are never great for your memory and thinking. The longer you're on it, the harder it is to get that effect to go away.
There are three windows of risk here:
You can get memory problems from the get-go when you take them, even one-time use. Now, we don't think you'll get permanent damage immediately, but even with short-term use, you can have a memory problem.
Then there is when you've been on them a while, chronic use. Let's say months. It can take months for that effect on your memory to wash out. Usually, in our clinic, we want to see people at least three months out from stopping an anticholinergic drug to reassess how their memory and thinking are doing.
Then there are long-term effects. There has been mounting evidence over the decades that there is an association between anticholinergic drugs and dementia, specifically Alzheimer's disease. Alzheimer's disease pathology, preferentially, hits the networks of the brain that use acetylcholine.
WebMD: Are some people more at risk for negative brain effects than others?
Finney: As you get older, you get more susceptible to drug side effects. When you're young, you can really get thrown off-kilter by various health factors, and your body snaps right back. The older you get, the harder it gets to snap right back to center and stay healthy. So we have to be more vigilant. And that's doubly so for anticholinergic drugs. The other part is we know that the things that cause neurodegenerative dementias – those pathologies are age-related. The older you get, the more likely you are to start accumulating the start of those pathologies.
A recent study in Neurology found that anticholinergic drugs increased the risk of mild cognitive decline and cognitive decline, especially for people who have a genetic risk for Alzheimer's disease (the apolipoprotein E4 or ApoE4), increased sensitivity for dementia, and those already showing signs through a biomarker for Alzheimer's pathology.
Another analysis in JAMA Internal Medicine found a link between anticholinergic medications and increased dementia risk for people 55 and older. The study found older people who had total anticholinergic exposure of more than 1,095 total standardized daily doses within a 10-year period had 50% higher odds of experiencing dementia. That’s equivalent to three years of daily use of a single strong anticholinergic medication at the minimum effective dose recommended for older people. The associations were strongest for anticholinergic antidepressants, bladder antimuscarinics, antipsychotics, and antiepileptic drugs.
WebMD: What advice do you have for people taking anticholinergic medications?
Finney: I would say if you're having a one-time severe reaction to something and you need an anticholinergic antihistamine like Benadryl, that might be reasonable. One-time use is probably not a big deal. It's more frequent use that is the problem. Even for severe motion sickness, you might take an anticholinergic medication, but just realize you might lose some memories for a little bit.
However, we really ought to be exhausting all other behavioral, environmental, and non-anticholinergic medication and treatment options before we're even thinking of turning to one that's anticholinergic. If you’re unsure whether the medication you’re taking has anticholinergic effects, ask your provider. Overall, avoiding anticholinergic drugs and drugs with anticholinergic effects is important for your brain health.
WebMD: What are some alternatives for managing conditions like allergies, depression, and some of the other conditions we discussed?
Finney: If you’ve got sleep problems, really, the first goal is good sleep habits. Make sure you're going to bed at the same time every night. Nothing with a screen after bedtime. Stay in bed if you can, but after 15 minutes, if you're not asleep, get up and do something else for 15 minutes without the light, without the screens, and then go back to bed. You can use over-the-counter melatonin if you need to.
For anxiety and depression, we have a lot of medication options without the anticholinergic effects. Duloxetine, for instance, can treat depression and pain. Counseling is still a really powerful tool. We usually recommend at least every other week to make progress, ideally weekly. Even with severe anxiety and depression, we've got other tools. For example, transcranial magnetic stimulation.
For urinary incontinence, there are some newer-generation medications that don't have this anticholinergic risk, like mirabegron. For most chronic pain, physical therapy is the mainstay and has more evidence of helping pain than drugs do. For allergies, we do have a lot of over-the-counter newer class options, like cetirizine, fexofenadine, and levocetirizine. But be careful of any over-the-counter medications that have DM on the end. More often than not, they have diphenhydramine in them.
I think the good news is we've got a lot more options than we used to for treating these really important conditions.
