Common anticholinergic drugs like Benadryl linked to increased dementia risk

Beverly Merz
Beverly Merz, Executive Editor, Harvard Women's Health Watch

One long-ago summer, I joined the legion of teens helping harvest our valley’s peach crop in western Colorado. My job was to select the best peaches from a bin, wrap each one in tissue, and pack it into a shipping crate. The peach fuzz that coated every surface of the packing shed made my nose stream and my eyelids swell. When I came home after my first day on the job, my mother was so alarmed she called the family doctor. Soon the druggist was at the door with a vial of Benadryl (diphenhydramine) tablets. The next morning I was back to normal and back on the job. Weeks later, when I collected my pay (including the ½-cent-per-crate bonus for staying until the end of the harvest), I thanked Benadryl.

Today, I’m thankful my need for that drug lasted only a few weeks. In a report published in JAMA Internal Medicine, researchers offers compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia.

Anticholinergic drugs block the action of acetylcholine. This substance transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory. In the rest of the body, it stimulates muscle contractions. Anticholinergic drugs include some antihistamines, tricyclic antidepressants, medications to control overactive bladder, and drugs to relieve the symptoms of Parkinson’s disease.

What the study found

A team led by Shelley Gray, a pharmacist at the University of Washington’s School of Pharmacy, tracked nearly 3,500 men and women ages 65 and older who took part in Adult Changes in Thought (ACT), a long-term study conducted by the University of Washington and Group Health, a Seattle healthcare system. They used Group Health’s pharmacy records to determine all the drugs, both prescription and over-the-counter, that each participant took the 10 years before starting the study. Participants’ health was tracked for an average of seven years. During that time, 800 of the volunteers developed dementia. When the researchers examined the use of anticholinergic drugs, they found that people who used these drugs were more likely to have developed dementia as those who didn’t use them. Moreover, dementia risk increased along with the cumulative dose. Taking an anticholinergic for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.

The ACT results add to mounting evidence that anticholinergics aren’t drugs to take long-term if you want to keep a clear head, and keep your head clear into old age. The body’s production of acetylcholine diminishes with age, so blocking its effects can deliver a double whammy to older people. It’s not surprising that problems with short-term memory, reasoning, and confusion lead the list of anticholinergic side effects, which also include drowsiness, dry mouth, urine retention, and constipation.

The University of Washington study is the first to include nonprescription drugs. It is also the first to eliminate the possibility that people were taking a tricyclic antidepressant to alleviate early symptoms of undiagnosed dementia; the risk associated with bladder medications was just as high.

“This study is another reminder to periodically evaluate all of the drugs you’re taking. Look at each one to determine if it’s really helping,” says Dr. Sarah Berry, a geriatrician and assistant professor of medicine at Harvard Medical School. “For instance, I’ve seen people who have been on anticholinergic medications for bladder control for years and they are completely incontinent. These drugs obviously aren’t helping.”

Many drugs have a stronger effect on older people than younger people. With age, the kidneys and liver clear drugs more slowly, so drug levels in the blood remain higher for a longer time. People also gain fat and lose muscle mass with age, both of which change the way that drugs are distributed to and broken down in body tissues. In addition, older people tend to take more prescription and over-the-counter medications, each of which has the potential to suppress or enhance the effectiveness of the others.

What should you do?

In 2008, Indiana University School of Medicine geriatrician Malaz Boustani developed the anticholinergic cognitive burden scale, which ranks these drugs according to the severity of their effects on the mind. It’s a good idea to steer clear of the drugs with high ACB scores, meaning those with scores of 3. “There are so many alternatives to these drugs,” says Dr. Berry. For example, selective serotonin re-uptake inhibitors (SSRIs) like citalopram (Celexa) or fluoxetine (Prozac) are good alternatives to tricyclic antidepressants. Newer antihistamines such as loratadine (Claritin) can replace diphenhydramine or chlorpheniramine (Chlor-Trimeton). Botox injections and cognitive behavioral training can alleviate urge incontinence.

One of the best ways to make sure you’re taking the most effective drugs is to dump all your medications — prescription and nonprescription — into a bag and bring them to your next appointment with your primary care doctor.

Comments:

  1. Joe

    Took a look at the study
    The diffence between the people that were in the non users and heavy users is massively different. 3x higher on EVERY risk factor stroke, obese, etc.. Odd this would get so much traction with the press.. Borderline irresponsible of Harvard to publish this on their blog. Nothing here even hints at causality

  2. Joe

    here is what the experts say. Also people have been taking bendryl for 70 years, over the counter for 30 years. If this was causing dementia the rates would be increasing..
    EXPERTS COMMENT
    Dr. Knopman said that it was “highly unlikely” that the drugs themselves were the direct cause of the dementia, adding that the ultimate underpinnings of the article have a strong biologic basis.
    Anticholinergic drugs “affect the area of the brain that facilitates learning and memory, and that’s the basis of the cholinergic model of Alzheimer’s,” he said. “That pharmacologic profile probably has negligible impact on people under 60, but with people with incipient dementia, the drug probably exacerbates the symptoms.”
    Dr. Knopman said the main limitation with a prospective study is an indication bias. He suggested that the use of these drugs might be because of incipient dementia, rather than the drugs themselves causing the dementia.

  3. Hank

    Trouble sleeping, especially past middle age?

    Worth considering: your body makes as much melatonin as it needs but only starts to do it after the last blue light goes away in the evening — if you let it.

    Blue light has a dark side – Harvard Health
    http://www.health.harvard.edu/staying-healthy/blue-light-has-a-dark-side

    http://www.health.harvard.edu/press_releases/light-from-laptops-tvs-electronics-and-energy-efficient-lightbulbs-may-harm-health

    You can find yellow “bug light” bulbs cheap, or amber “turtle safe” lights.

    (The blue light ‘wakeful/attention’ switch is evolutionarily very, very old. Daytime sky light color — Florida protects baby turtles so they go toward the ocean instead of toward the freeway)
    — or any automotive supplier has 12-volt “clearance” amber LED lights. Remember there’s a spike of blue in even “warm white” lights. You can see it.

    That’s what drives the phosphor that emits the rest of the color.

    Harvard University
    May 1, 2012 – Light at night is bad for your health, and exposure to blue light emitted by electronics and energy-efficient lightbulbs may be especially so.

  4. Karen

    I’ve been taking diphenhydramine for three years, and have been noticing a definite decline in short-term memory and the ability to retrieve the word I need. Have been blaming it on the job being more stressful than it seems. Stopped taking it around Valentine’s Day when I first came across the info being discussed here. Have just in the past day or so noticed a little lifting of the fog, but I also take supplements specifically for brain, and meditate. Maybe has something to do with quicker recovery. Experience has shown me DHA has the most noticeable effect, at least at short-term. For brain I also take B Vites and ginkgo. So I don’t know that everyone would feel some recovery that quickly, or that I’ll recover completely. But I think I will, and will use my newly recovered mental powers to search out ways to enhance that recovery. So good luck all; you’re on a computer here, won’t find a more convenient way to research what you need now.

  5. Political Cynic

    May I just point out that this article, as presented, is meaningless.

    54 percent increase FROM WHAT? Without knowing the relative distributions of people in control and non-control groups this tells us nothing.

    Was the risk 1/100 increased to 1.5 in 100? Was it 25/100 increased to 37.5/100?

    Learn how NOT to lie with statistics please…

    • Richard

      Obviously, it was not 1/100 with an increase to 1.5/100. Far more than 1% of the population acquires dementia. You make a valid point though. I was thinking the same thing you were. If 17% of the population acquired dementia without taking the suspected drugs, and 26% of those who took the suspected drugs acquired dementia, it does lead to some suspicion though. Like you said, we need to see the exact numbers.

      • b shafer

        Meaningless? I believe data are in the article. Were there not 3500 in the study? Did not 800 acquire dementia? Was the differential 54%? Then i think x + .54x + x = 800 tells you how many would get dementia without the anticholinergics (x) . . . or . . . something like that (i took algebra a very, very long time ago . . . so i may have that wrong . . . but the data are given . . . overall chance of developing dementia would be 800/3500 . . . but for the takers of the anticholinergics, it would be 54% higher, if i remember the article right [of course i am 73 . . .]). I give my tiny dog Benadryl every night for her itchy feet–guess that has to stop! (I am not sure how a demented dog behaves, though . . . .) Memory (especially for proper nouns and then for nouns) gets worse and worse for all of us my age, far as i can tell. No point in tempting fate! As for melatonin, the dreams with melatonin seem to be disturbing for all of us . . . . most of us decide it is not worth it. – b

  6. Cece

    Hi, thanks for the informative research link. There is always the risk of any medication, and it is challenging to know which poses the greater risk-allergicic reaction, untreated depression, or insomnia.

    I have read too that Melatonin is also not without risk as the hormonal effects for older folks causes problems, and that is best used as a short term reset for sleep disorders.

    Gloves, face masks, good sleep hygiene, and increasing activities that improve our quality of life seem all the more necessary when faced with damage from the pharmacopeia approach to allergies, sleep disorders depression, and lack of physical conditioning. Just a thought.

    Thanks for a great discussion

  7. Tim

    Recently I lost my COBRA coverage. It was very expensive but they kicked me out and the only insurance I could get is MediCal. Today I met my new primary care MD (newly minted Resident). I asked for a refill of oxazepam that I have taken for 15 years without any problem. The doctor did not want to fill it. He recommended melatonin, benadryl and Elavil. So he wanted to give me a combo of anitcholinergics. I told him I have tried each in the past with poor results. I also mentioned this research as a concern. His reply, “I have read the information”. End of discussion. He suggested I might need to find another doctor unless I want to take his Rx. Disappointing.

  8. elizabeth kang

    I believe I have an early s/s of dementia caused by the benadryl and I am scared to death at this point 2/24/15. I took 200mg Benadryl for allergies in Texas (lots, lots of allergies in TX) for about 15 years. The prescription was read, Benadryl 50mg po qid. My husband is a physician, and his friend who also is a physician whote the prescription for me after seeing an horrible allergy attack and the trip to the ER for anaphylactic episode. About 5 to 6 years later I started to noticed that I was forgeting names (but could see the face of the person in mind’s eye, just can’t bring the names up), often can’t find the things. I often don’t remember what I have done minutes before I start another project thus running the car in the garage for hours… it just wanted to warm up the car before take off but changed mind to do another project. I also left house while the eggs were boiling in the kitchen… when I came home after having a lunch with friends, the house was full of the smoke… I also not showing up at the dinner party which was for my honor. They said a week before and I agreed to be there.

    My family has no history of dementia.
    No one told me about long term use of the dementia effect from the Benadryl. I told my FPs & other specialists (when I see them for other reasons, but they do the medication inventory on new pt); they never questioned me taking such a high doeses of the Benadryl for all these years… now what should I do? I understand this is a permanent state. No way to cure it. Please help me.

    • Richard

      What you are experiencing is not necessarily early signs of dementia. Talk to your husband more about this. I did similar things as you when I was in my twenties and thirties. I am not in my fifties and am not any worse. There can be many reasons for forgetting. Stress, fright, ADD, and medications to name a few, can all cause this to happen. I think 200 mg of benedryl is too much though. I have severe allergies myself. The allergist said I am one of his ten worst patients. I limit the benedryl to 25 mg a day though.

  9. Lee

    I’m a White Male age 77. I’ve been taking one Benadryl and 10 mg Melatonin for sleep for the last 27 years and haven’t noticed any dementia although I do read slower to fully comprehend what I read.

  10. Lisa

    I have been taking Benedryl for years for insomnia. Occasionally I will take Ambien or Melatonin. I never take more than 1/2 tablet and probably average 2-3 Tylenol PM/Alieve PM a week. Any suggestions as to what to take instead? And, at 52 years, will there still be long term affects if I stop now?

  11. louisabt

    Thank you for the informative article. I am worried about the medications my husband (age 81) is taking. Both over the counter (Advil PM, contains diphenylhydramine) and the prescription drugs you mentioned. He has complained about brain fog. Will double check all his medications for interactions and/or anticholinergic actions.

  12. Gioia

    I have panic attacks and allergies and the best alternative to some drugs (xanax and 12/24hr. allergy pills that didn’t work). I have been taking Benedryl almost regularly for the past 5 yrs. I would take up to 4 doses a day during my allergy season and at least 1 or 2 doses every other day! My question is since I quit taking it about 2 wks ago…..will the effects be reversed or am I simply keeping the dimentia symptoms from coming on faster and harder or whatever. Will I get better and be back to me? Or am I screwed!!!!

  13. Allie

    Where does one find ACB scores for specific drugs?

    • Hugh

      Hello. The article has a link to most drugs that can be categorized A, B or C in the last paragraph. The point is that all of these drugs have some degree of “anti-muscarinic” effect. They are all anticholinergics. If your meds are not on this list, they are probably not anticholinergics. You can google your specific drugs and just read to see if any of them are anticholinergics. This is the key word: anticholinergic.

  14. aditidung

    Your information is really useful and interesting..Thanks for sharing this great article…

  15. Leiza

    These results and understandings on the detriment to memory by many commonly prescribed and over the counter medicines is just beginning to be written up in medical literature. Your family physician might not be aware of the information. Print this and other articles and bring them with you to the doctor. Ask your doctor to look into these findings. Changing medications is a viable alternative, and in some cases discontinue using others. You are your own best advocate for health and well being. Doctors are well learned and intelligent- but that doesn’t mean they always know what is best for you and your loved ones. In the end you are in charge of your own body and possibly the body of someone who relies on you to be their eyes and ears.

    • ben

      And I like to find the physician that will take the time to actually go through this bag of meds. We are lucky to get face to face time with the physician for more than 8 minutes and to answer one or two of our questions…..

      • Marg

        I really think that a lot of physicians do not realize the results of this study. As a medical transcriptionist, sometimes an elderly patient would be taking over 25 drugs, the majority prescribed. A pill to alleviate the symptoms of another pill. Polypharmacy is rampant. A good doctor will study the pharmaceuticals. Another will just prescribe. Don’t doubt me. I typed these patient’s clinic notes, discharge summaries and consults for 43 years.

  16. colleen

    I still believe that it’s Diabetes of the brain.

  17. vimeo.com/49417426

    I would like to promote my Video on Vimeo about water scarcity around the world and the humanitarian crises in Sudan.
    HALEEMA was screened on countless festivals and is now available on Vimeo.

  18. deg

    Do the researchers have any advice for those already suffering from dementia? My wife has dementia, and just last week I questioned her urologist about the medications she was taking. He said they were standard and effective drugs to help control her bladder. After seeing this article, I checked lists of anticholinergic drugs and found imiprimine, one of the drugs she takes, on the list. Is this likely to make her mental condition worse?

    • Andrea

      I don’t know about researchers, but I know from my own experience about my mother suffering dementia and being on lots of anticholinergic drugs (including oxibutinine, an incontinnece drug), for many many years, that discontinuing the drugs can ameliorate dementia symptoms and in some extent halt its progress. Doctors are however reluctant to admit this and to advice drug discontinuation (I discontinued all of my mom drugs and found out they were doing no good at all: actually incontinence problems were caused by another anticholinergic drug from the benzodiazepines family. I am not in the US or Europe where probbaly I could face legal problems by not following Drs instructions).

      • pharmd

        First of all, it is obvious you are not in the US. We in America are free and do not have to take meds if we so choose so why would you think you would face legal problems? Secondly, NO benzodiazepine is an anticholinergic!!! You obvously have no medical knowledge so don’t post about things you know nothing of

      • PNW

        You are right , Andrea, that caretakers in the United States who disagree with treating doctors and want second opinions face legal abuse. Justina Pelletier was just once case that got a lot of publicity.

      • FionaM

        There isn’t any risk of legal problems in the UK either, and I would be very surprised if there would be any in other European countries.

        In the UK ,and probably many other countries, its illegal to use drugs like morphine,heroin or cocaine , but I don’t think that you are talking about those. And that is about *taking* a drug where its illegal, not *stopping taking* a medicine.

    • Andrea

      Posted a reply but I don’t see it

      • Rich Riffe, JD

        My Dear Andrea:

        While it is true that benzos are not anticholinergic, PharmD misses the forest for the trees when s/he scolds you for not being – well, a PharmD. Moreover, PharmD’s rant about your commenting on something “you know nothing about” is from waaay out in left field. You have raised a GREAT issue.

        What PharmD MEANT to say is that “while benzodiazepines are not anticholinergic, you have made the important discovery that they aggravate your relative’s dementia”. Thirty years of litigation have lead me to conclude that folks worry more about legal liability than need be; however, you can help alleviate your fears by becoming her medical power of attorney. If no relatives will contest your application you don’t even need a lawyer and can get the proper forms from the office of the Clerk of the Court which handles guardianship and conservatorship in your venue.

        Oh, and PharmD, since you are claiming the “doctorate” title, please use proper grammar and punctuation. Your rant should end, “about things of which you know nothing”, and put one of those little “dots” (aka a period) at the end of your sentence.

  19. Haym Solomon

    Perhaps one should consider that Parkinson’s and other Dementia- spectrum diseases have an early symptom of not being able to get to sleep. That being said, did the research consider that study participants might self medicate for insomnia ….years before the onset of Dementia , or recognition and diagnosis by a health care provider? Cart or the Horse?

  20. Helen

    The information is useless unless the specific drugs are named. My husband has Parkinson’s, which drug should he not be taking and what is the substitute? Is there any place other than Harvard where I could find out more?

    • John Traylor

      My wife has parkinsons disease also. Would you mind sharing with me what you might have learned about which medications to take and not to take. Would appreciate your sharing any other data or experiences, or anything that might be helpful.
      Thank you,
      John Athens, Ga.

    • MH White

      You can probably find out about specific drugs by asking your pharmacist. A good one may be more up-to-date about the side effects of particular drugs than physicians have time to be. Also, check the website for “The People’s Pharmacy,” the radio show. I believe they have a list in one of their books.

  21. pmw

    Scary article considering I have been using benedryl every night for sleep for the past ten years. My primary care doctor told me it’s fine and that’s why most people take the drug. My question is whether stopping will reverse the damage.

    • Terry

      I have been taking them for sleep also for years…my doctor knew this and did not warn me of dementia side -effects either. I wonder if the damage will subside some if we stop taking them..or is the damage permanent?

      • Francios

        I wouldn’t worry about it. I have been taking benadryl for years also. Although, I will stop taking the drug and replace it for melatonin,

    • Carol

      I too have been taking Benadryl to help me sleep for about two years. I only take half a caplet but still very scary. Need to find something else or just not sleep, better than the alternative. Thanks for your post.

  22. Taufiq Zuhdi

    Thanks for sharing. I will wait for your writing again.

  23. Malcolm Kyle

    All of these dangerous medications can be replaced with a far healthier alternative, marijuana.

    Researchers have found that there are no differences between daily marijuana users and those using no marijuana in their use of the emergency room, in hospitalizations, medical diagnoses, or their health status.
    
”Researchers from Boston Medical Center (BMC) and Boston University School of Medicine (BUSM) studied 589 adults who screened positive for drug use at a primary care visit. Those patients were asked about their drug use, their emergency room use and hospitalizations, and their overall health status. In addition, information about other medical diagnoses was obtained from their medical records. They found the vast majority of the study sample (84 percent) used marijuana, 25 percent used cocaine, 23 percent opioids and eight percent used other drugs; 58 percent reported using marijuana but no other drugs. They also found no differences between daily marijuana users and those using no marijuana in their use of the emergency room, in hospitalizations, medical diagnoses or their health status.”

    • Hugh

      Hi Malcolm. I don’t doubt that you have found an article supporting your use of marijuana and it may indeed have veracity. However, chronic smoking of marijuana can have detrimental effects on the lungs; and of course smoking it can make it difficult to control the dose. I know of anecdotal accounts of marijuana helping with insomnia but I’m not sure that has been proven and paranoia is a known side effect which would, of course, inhibit sleep. I’m all for the drug being legal, but we need more data.