Senior Man, arms crossed, looks down at large assortment of prescription pill bottles, wrong medicines

Here we go again, with headlines that sound like they could be hype:

“Hay-fever drugs linked to Alzheimer’s” (Irish Independent)

“Over-the-counter pills could raise risk of Alzheimer’s: study” (New York Post)

“Common allergy, depression meds may increase odds of dementia” (CBS NEWS)

“Dementia ‘linked’ to common over-the-counter drugs” (BBC News Health)

These headlines are scary. Should you be concerned? In a word, yes!

Researchers studied participants in the Adult Changes in Thought (ACT) study conducted in the Seattle area (JAMA Internal Medicine, online, Jan. 26, 2015). These were older people enrolled in an integrated health care delivery system called Group Health. Over 3,000 individuals were included in the research, and none had dementia when they entered the study starting in 1994.

Scientists tracked their drug use and cognitive function over the next two decades. The higher the dose of anticholinergic drugs and the longer such medications were taken, the greater the risk of dementia. In this study the most common anticholinergic drugs were antihistamines found in over-the-counter allergy drugs and nighttime pain relievers, antidepressants that are also prescribed for nerve pain and medications prescribed to treat incontinence or symptoms of overactive bladder. The authors conclude:

“Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.”

The Evidence Keeps Accumulating:

In the BMJ (formerly the British Medical Journal) an article was published on April 25, 2018 reinforcing the relationship between anticholinergic drugs and dementia. The authors concluded:

“Many people use anticholinergic drugs at some point in their lives, and many are prescribed to manage chronic conditions leading to potentially long exposures. There are robust associations between levels of anticholinergic antidepressants, antiparkinsons, and urologicals and the risk of a diagnosis of dementia up to 20 years after exposure.”

What Are Anticholinergic Medications?

We have been writing about this category of drugs for a very long time because of a clearly established link to cognitive impairment. These medicines are known as anticholinergics because they interfere with the ability of a crucial brain chemical called acetylcholine (Ach) to attach to nerve cells. ACh is essential for muscle contraction. Without adequate amounts of this neurotransmitter you could not breathe, blink your eyes or tie your shoelaces. Body movement can only happen when ACh triggers a muscular contraction.

Acetylcholine is also critical for proper brain function. Without ACh doing its job transmitting messages between brain cells, you would become forgetful and confused.

Twilight Sleep for “Painless Childbirth”

One of the most potent anticholinergic medications, scopolamine, was used for decades with a narcotic like morphine to induce “twilight sleep.” Starting about a century ago, women were given this combo during labor and delivery so they wouldn’t remember the pain or anything else about the experience. The German researchers who developed this approach in the early 20th century said that it produced:

“clouded consciousness with complete forgetfulness.”

Modern-Day Anticholinergics

Most physicians are offered a few hours of training about anticholinergic drugs (at best). They are taught about belladonna, aka deadly nightshade. (The drugs atropine, hyoscyamine and scopolamine were derived from the plant Atropa belladonna.) Such medications have been used to treat diarrhea and what was once called “spastic colon.” The combination of atropine and diphenoxylate (Lomotil) remains popular for diarrhea.

Scopolamine (Transderm Scop) is still prescribed for motion sickness, and ophthalmologists and optometrists may use atropine drops to dilate the pupils during an eye exam. Doctors also employ other anticholinergic drugs such as ipratropium (Atrovent) and tiotropium (Spiriva) for asthma. Anticholinergics such as fesoterodine (Toviaz), oxybutynin (Ditropan) and tolteradine (Detrol) are frequently utilized to control the symptoms of overactive bladder.

Popular Antihistamines & Sleep Aids

What most modern-day physicians have not learned, however, is that many other drugs also have anticholinergic activity. As mentioned in the ACT study, first-generation antihistamines were linked to dementia. We are talking about drugs like chlorpheniramine and diphenhydramine (DPH).

You may be surprised where DPH shows up. It is the primary ingredient in many allergy and hay fever meds including the popular brand name Benadryl. But DPH is also found in a huge number of nighttime pain relievers and sleeping pills. Look at the label of Advil PM, Aleve PM, Bayer PM, Excedrin PM, Nytol, Simply Sleep, Sominex, Tylenol PM or Unisom and you will likely find diphenhydramine as a key ingredient.

We do not worry very much about the occasional use of such drugs. But chronic use, day in and day out for both pain and insomnia, begins to add up to substantial anticholinergic exposure.

Antidepressants

The researchers noted that an older class of antidepressants called “tricyclics” was also linked with dementia. Drugs such as amitriptyline or doxepin are not prescribed as much for depression as they once were. That’s because of newer antidepressants such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac) and sertraline (Zoloft). But some physicians prescribe amitriptyline for nerve pain and doxepin for insomnia. These drugs can produce classic anticholinergic side effects: dry mouth, constipation, blurred vision, rapid heart rate, difficult urination, confusion, cognitive impairment and drowsiness.

Bladder Drugs (Urinary Incontinence)

In the ACT study the most common anticholinergic drug in the class of meds for overactive bladder was oxybutynin (Ditropan). Other medicines in this category include fesoterodine (Toviaz), and tolterodine (Detrol). By the way, an over-the-counter form of oxybutynin is now available for women under the brand name Oxytrol.

Here’s the Real Problem:

What concerns us far more than any individual anticholinergic medication is the combination of several drugs with anticholinergic activity. Physicians may not realize that the anti-anxiety agent alprazolam (Xanax) has anticholinergic activity. So does the ulcer drug cimetidine (Tagamet). The dizziness drug meclizine (Antivert, Bonine) also has this activity.

We could go on and on, but by now you get the picture. There are dozens of medications that have this property. Someone taking Tylenol PM to get to sleep who is also taking amitriptyline to ease nerve pain along with oxybutynin to control an overactive bladder could end up disoriented and forgetful. But don’t take our word for it. Here are stories from visitors to this website:

C.S. writes:

“Many years ago my urologist prescribed Ditropan and I took the drug for about four years. I had an hour’s drive to work each day and I began to realize that many days I could not remember the drive and would arrive at work with my mind in a somewhat “fuzzy” state. I happened to pick up a new prescription for Ditropan at the pharmacy and started reading the side effects of the drug.

“I saw that my symptoms could be connected to the drug. I stopped taking the drug immediately and decided that I would try to control my bladder some other way (exercises, etc). My symptoms went away and I have not had any problems since. I still cope with bladder issues but I would rather be clear-headed.”

Robert adds:

“I was prescribed amitriptyline for headaches and couldn’t stop sleeping! I also felt sluggish mentally and pretty much dead overall. It was an awful feeling.”

This comment comes from Abigail:

“I appreciate your warning about anticholinergics. I only took Lomotil for IBS [irritable bowel syndrome] when I went out for an event, so I thought my episodes of brain confusion were caused by senior moments. After your warning I realized I was taking an anticholinergic. I stopped taking Lomotil and have regained my mental clarity. Thank you!

Who Takes an Anticholinergic Drug?

You might wonder how many older people are on anticholinergic medications. According to the Seattle team of researchers, 8% to 37% are taking such drugs, despite warnings to health professionals that risks might outweigh benefits. In other words, as many as one-third of people over 65 could be taking an anticholinergic drug without even knowing it. The authors of the study point out that this may not be reversible:

“The general view is that anticholinergic-induced cognitive impairment is reversible on discontinuation of medication therapy. However, several investigators have reported that anticholinergics may be associated with an increased risk for sustained cognitive deficits, such as mild cognitive impairment or dementia. One biologically plausible mechanism for these findings is that cumulative use of these agents results in pathologic changes in the brain similar to those observed with Alzheimer disease (AD).”

Most Doctors Don’t know Which Drugs Are Anticholinergic

As mentioned earlier, medical students get an hour or two training about anticholinergic medicines. They learn about atropine, hyoscyamine and scopolamine, classic drugs in this category.

What they don’t always learn is how many other medications also have anticholinergic activity. If you ask your doctor whether cimetidine (Tagamet), Lasix (furosemide) or alprazolam (Xanax) could have anticholinergic action, the chances are pretty good that you would be told no. But the list of such drugs is surprisingly long.

Learn More!

Here is a link to a list that we have prepared. We must emphasize that no one should EVER discontinue any drug without first checking with the prescriber! That said, the Seattle team of researchers suggests that:

“Prescribers should be aware of this potential association [the increased risk for dementia in people with higher-use of anticholinergic drugs] when considering anticholinergics for their older patients and should consider alternatives when possible. For conditions with no therapeutic alternatives, prescribers should use the lowest effective dose and discontinue therapy if ineffective.”

Would you like to know more about how medications can affect brain function? We have much more information in our chapter, “The Screwing of Senior Citizens.” In addition to a list of anticholinergic drugs, there is a long list of medications that older people should generally avoid (The Beers List). This information can be found in our book, Top Screwups Doctors Make and How to Avoid Them.

We would be derelict if we didn’t point out that this is not the first study linking anticholinergic drugs to dementia. In our book we describe the “Three-City Study” from France. These investigators concluded that

“elderly people taking anticholinergic drugs were at increased risk for cognitive decline and dementia. Discontinuing anticholinergic treatments was associated with a decreased risk.”

In addition to the long list of anticholinergic drugs, researchers have also discovered that benzodiazepine drugs frequently used to calm anxiety or aid sleep are also associated with a greater risk of dementia (BMJ, online Sept. 10, 2014). A problem became apparent in older people who had taken such medicines for at least three months, but the longer they had been on the drugs, the higher their risk of an Alzheimer’s disease diagnosis. If you would like to read more about that study, we have written about it.

What About You?

Lest you think this is only an older person’s problem, we hasten to point out that middle-aged and younger people can also experience anticholinergic side effects. Just because you are 57 does not mean you are immune to these complications.

Health professionals need to be far better educated about anticholinergic pharmacology and its consequences on the brain. And patients need to ask their physicians, nurse practitioners and pharmacists whether any of their medicines have anticholinergic activity.

You may find this article from May 14, 2018 of additional interest:

Does Popular OTC Antihistamine Increase Risk of Dementia?

Please share your own story below.

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  1. Nell M.
    UT
    Reply

    Side affects of drugs and pills have been my concern since the passing of my husband. Research showed that many of the drugs drs prescribed had the same side affects. Those made his life miserable, as he fought what the doctors said was just the affect of old age. Thank you for this article. I can see I need to be more careful even about OTC drugs.

  2. Kim
    Reply

    Please follow up with info on anesthesia and dementia for those over 65.

  3. Sue
    Greensboro,NC
    Reply

    I have searched for an antihistamine without the acetylcholine activity too, but with little success.
    And if you mention it to a Dr. or pharmacist, their eyes glaze over, and they tend to change the subject.

  4. Gary
    Utah
    Reply

    I have experienced loss of memory with Eliquis: In 2015 I was prescribed Eliquis, and immediately I started to experience memory loss: I would go into a room and not remember why. After two weeks I stopped taking Eliquis, and the condition stopped. However, after just two weeks on this drug my memory has not been as sharp as it formerly was.
    For example: I could remember names: Now I cannot remember names to the extent that I formerly could.

  5. Carlton S.
    Reply

    Dr. Perlmutter in a recent interview reported that newly published studies showed a significant increase in the risk of dementia for those taking drugs for acid reflux – PPI’s.
    A 44% risk increase

  6. Angie
    Oregon
    Reply

    I have been taking Amitriptyline since 1990. I had problems sleeping and severe depression. Over the years I had gained a lot of weight. Two years ago I warned myself off a dosage of 125 mg. I lost 60 pounds, but my problems with sleep and depression came back. I’ve tried two different antidepressants, but none help me sleep. After not sleeping well for a few days I can’t concentrate on anything and I have no energy.

    I’m to the point of throwing caution to the wind and taking Amitriptyline to get sleep and have quality of life instead of trying one medication after another, feeling sleep deprived and not enjoying my life.

    Someone mentioned a otc medication similar to Amitriptyline. What is it called?

  7. Sharon
    Reply

    I have a sister-in-law whose children are at their wits end dealing with her mental and physical decline. She lives in a lovely large duplex which she now will have to vacate and go into a nursing home because she is imagining that her dead husband is calling her from the lower level of her home. She was preparing to attend a wedding the other day. The trouble is there was no wedding to attend. She asked her son to give her the phone number of her dead husband, and said that he was cheating on her. She takes MANY medications!

    She told me years ago that she would get lost traveling to their acreage outside of Altoona, Iowa. Not ONE of her children have even checked her medications to see if any of them would be causing her bizarre behavior. She has taken an antidepressant for years and has had many falls causing possible concussions. Many of the heart medications and blood pressure meds warn ‘beware of falls’ on their side effects. I am sick at heart to think that if I mention this information I will be totally ignored, and their mother will be in a dreaded nursing home instead of her wonderful comfortable large duplex.

  8. Tom
    Scotland
    Reply

    I was put on a high dose (either 200mg or 250mg…can’t quite remember) of the anticholinergic drug clomipramine in 2007 (at age 19) which I took for five years. Some of the side effects I experienced include huge increases in the time I spent sleeping (up to 12 hour per night), putting on 20kg of weight and substantial increases in the amount I was sweating (had to have 2 or 3 showers a day to try combat the effects of this).

    More relevant to the article (ie. from a cognitive perspective) I found it incredibly difficult to learn new skills (to the point of dropping out of further education twice within the five years I took the drug) and struggled to learn even basic skills at the (unskilled) job in retail I had at the time. My behaviour in my social life changed as well, initially for the good but ultimately for the worse (possibly due to the combination of the antidepressant with excessive alcohol consumption) which led me to getting into some really dangerous situations, eventually concluding with a temporary brain injury and short hospital stay which made me realise just how out of hand my life had become.

    To cut a long story short – this drug is awful. It completely messed me up as a person and swallowed up a decent chunk of my life that I can barely remember (even though it was fairly recently and I’m only 29 now). I was not warned about the how badly it would affect my cognitive abilities (my memory and ability to learn has definitely improved in the five years I’ve been clomipramine free, but I feel aren’t as good as they were prior to taking it) or behaviour (I become completely oblivious to danger and made a number of really stupid decisions which resulted in both embarrassing myself and emotionally hurting people close to me). In fact some of my friends have said it changed my personality and that at times my behaviour was bizarre to witness.

    Personally, I’d recommend avoiding this drug (or others with similar side effects) at all costs and asking your doctor for something different if you’re already on it.

  9. Annette
    Chicago
    Reply

    I appreciate the information you’ve provided as I’ve been taking Wellbutrin for depression over 8 years. My concern is that you suggest a purposeful intention (by doctors or the pharmacy industry) to give seniors drugs that are known to cause harm via a title like “the screwing of seniors.” Shame on you for that!

  10. Jamie
    Virginia
    Reply

    There is an over the counter version of Elavil called Elavil OTC Sleep that is reformulated without the anti-cholinergic ingredient amitriptyline that is in the prescription Elavil.

  11. Jennifer
    Minnesota
    Reply

    I have a myriad of health issues along with a strong family history of Lewy Body Dementia. I lost both my paternal grandmother & my father to the disease.

    I am 36 years old. My father began having symptoms when he was just 50 years old, & passed away 8 years later. When I was about 25, I began taking a tricyclic antidepressant, clomipramine (Anafranil). It caused me to have horrible cognitive problems along with many other unpleasant side effects. I had difficulty finding words, & would lose my train of thought mid-sentence. I had always been an avid writer, but I found I could no longer write more than one sentence. At the time however, I was very depressed & desperate for relief, so I continued taking it in spite of the side effects, & continued for 5 years.

    Somewhere along the way, my difficulty with verbal communication ceased along with most of the other side effects, but to this day, I have not been able to write like I used to. About 2 1/2 years ago, I began taking amitriptyline (Elavil) for Fibromyalgia. It worked to help me sleep & decreased my pain by 80-90%. I didn’t experience any cognitive or memory problems, however it caused excessive daytime sleepiness in addition to the significant fatigue I was already experiencing, so I began taking bupropion (Wellbutrin) to work as a stimulant & ward off the fatigue & daytime sleepiness. It worked like a wonder in this regard, & I also notice significantly improved mental clarity & memory.

    A few months ago, I stumbled across an article linking anticholinergic medications, including both clomipramine & amitriptyline with an increased risk of dementia. I’m already scared out of my wits about developing this devastating disease, & with my family history, I was very alarmed when I recognized medications I had been or was currently taking on the list. I began teetering down my dose of amitriptlyine immediately, & when I was able to see my Dr, I started taking gabapentin (Neurontin) in place of amitriptyline. In a previous comment, bupropion (Wellbutrin) was mentioned as having anticholinergic activity which really surprised me given that it is stimulating. Upon further investigation, I found this mentioned other places as well, though it is not on the list linked to this article.

    What I’m wondering now is, if I take a medication indicated as having anticholinergic activity, but experience a lack of cognitive, memory, or anticholinergic side effects, is it still increasing my risk? Aditionally, since gabapentin puts me to sleep, does that indicate anticholinergic activity & thus an increased risk also? And, since bupropion & has improved my cognition & memory improvement without any anticholinergic side effects, is it still increasing my risk simply based on the fact that it may have anticholinergic activity?

    Incase other people may be wondering the same thing about other medications, let me just ask this: If someone takes a medication with anticholinergic activity long term, but have a complete lack of anticholinergic side effects, is it still cumulatively increasing the risk of dementia? I am very interested in this topic, however when I google specific medications in regards to whether they have anticholinergic activity, I keep coming across the same lists repeatedly without being able to find much information in regards to other medications not listed. I would appreciate any discussion or input =)

    • barb
      Oklahoma
      Reply

      Dear Jennifer,
      You certainly can still write well!!!
      I’m so glad.

      An old editor

  12. CleverPseudonym2
    Wisconsin
    Reply

    First, thanks to all who are sharing their experiences here. I’m in my late 50’s and have been having some memory issues for a few years. Over the course of the last year, they have begun making it difficult at times to function.

    I’ve taken many anticholinergic drugs for many years – antidepressants, tranquilizers, incontinence drugs, anti-allergy drugs… and there is a strong history of dementia among my mother’s siblings. I am just now learning of the connection between these drugs and cognitive issues, thanks to a doctor who really knows her stuff. I have fears that some of the damage may be irreversible, though I have stopped taking the worst culprits.

    Memory/cognitive issues are starting to impact my daily life at this point – completely forgetting how to use equipment/objects that I have used hundreds of times, difficulties with written and oral communication/math/reading that have always come very easily to me. It sucks.

    • Stef
      Pennsylvania
      Reply

      I wonder the same thing. I have been on elavil for 20 years and ativan for 5 and my cognition is getting worse. I’m 43 and everyone I tell says it’s hogwash.

      • Cindy
        salt lake city
        Reply

        Same for me. I am 47 and have been taking Elavil for 12 years. Now having bad cognitive problems. It took me a while to figure out what the heck was going on, as I always had a sharp mind and memory. Finally, after doing research I found out that Elavil is an anticholergic drug. My doctor is prescribing me new medication. It’s really too sad since Elavil has helped my fibromyalgia. Sounds like a class action lawsuit to me.

  13. terry
    portland, oregon
    Reply

    So wondering if you are taking a drug with an anticholinergic, can one replace some of that by taking ACH or Choline? There are supplements with this in it, as well as certain foods high in choline. I take an over-the-counter sleep aid that contains doxalimine succinate and is the only medication including every RX sleep med known to man, and it’s better to sleep than to get 4 hours/night and waking up 6-8 x/night. And yes, I’ve had a sleep study as well as biofeedback, being hypnotized (really desperate obviously), exercise, Melatonin, etc. I take it every night and tried not taking it and was right back where I started with little to no sleep.

  14. Debbie
    MI
    Reply

    I’m 48. I have bad allergies and asthma, and I’m on an antidepressant. I just recently stopped taking benadryl for my allergies, I’m finding they are worse than I recall. I take Celexa for the depression, but we are in the process of weaning the dosage back. I also take Sudafed. I don’t see how I can stop this one though. The pressure in my sinuses can be horrible. I’m also forgetful. I have a full time job and three kids. How much of my memory issues are due to the drugs and how much for being really busy?

  15. yuki
    toronto
    Reply

    Are antibiotics that are prescribed for gum disease anticholinergic? They said some antibiotics are but not sure which are and which would be better to use. Dementia runs in the family and would not like to add to the risk but gum disease is rather serious.

  16. Brian
    Pennsylvania
    Reply

    My thoughts about this subject also pertain to the dangers of certain prescription drugs in general.

    I have always tried to emphasize to ANYONE taking an RX med; please, please educate yourself about what you are putting in your body. Just because it was given to you by a medical professional, doesn’t mean that you can nagivigate this territory with blind faith.

    And also, as “The People’s Pharmacy” tell us time and again; pharmaceutical companies don’t ALWAYS have our best interests in heart. (see generic medication debacle for example)

  17. Heather
    Milwaukee County
    Reply

    It is vry frightening that the drug companies have sold us as remedies the very compounds that may lead to our dementia. Tell me that they didn’t know about this!

    I wonder if there is any way to reverse the effects of anticholinergics that many of us have taken for years. I would sure appreciate an article or show about putting acetylcholine BACK into our brains. Is it possible? If so, is it risky? If it is ok, then how do we do that?

    Thanks!!

  18. Mark
    St. Louis
    Reply

    I’m a 54 year-old male who was diagnosed with a sleep disorder about 18 years ago. Basically, my mind went in and out of rem 60 times within 4.5 hours of sleep. I was prescribed Amitriptyline which changed my sleep tremendously for the good.

    About 5 years ago Bupropion was added to my medication list due to depression. I didn’t make a negative association with my medications until reading on this subject: In the past 3-4 years my eyesight has worsened to the point of getting prescription glasses last year, and my memory is worsening. My memory has been so bad that I got to the point of going to a specialist to test my memory. I was told my memory was, “typical for a man your age”, but I knew better. I am having problems at work; arguments have increased between my wife and I in the last year due to my forgetfulness on simple things like forgetting to put food away or forgetting to simply put a dish in the oven.

    My wife just read an article in our newspaper mentioning the Amitriptyline, and although it’s not a sure thing, it certainly makes sense to relate it to my increasing loss of memory of simple things these days. It’s time to look into this deeper. Thanks for the info on this site!!

    • Omicron
      Northampton, MA
      Reply

      That sleep disorder is called narcolepsy. Narcolepsy can also cause serious memory problems. Interestingly, people with narcolepsy have about 60% MORE histamine in their brains than people without narcolepsy. Doctors at Stanford now believe that histamine kills the neurons that secrete the chemical hypocretin (aka orexin), which is essential for maintaining proper sleep/wake cycles. Hypocretin neurons are completely, permanently dead in people with narcolepsy.
      I am beginning to wonder what role anticholinergics play in the development of narcolepsy…

  19. Toni
    Jamaica
    Reply

    I was diagnosed with depression as a teenager in the 90s, and was prescribed amitriptyline. I was drowsier than ever, and a “cloud” / “fog” was in my head, and my legs felt heavy and dead until I stopped. Is there any study on anticholinergic drugs in teens and young adults? Thanks.

    • Toni
      Reply

      Also, are SSRIs shown to have any such effect?

  20. JANET
    WA. STATE
    Reply

    I have been taking bupropion for chronic depression for over 20 years. I recently became aware of the increased risk of dementia as a result of taking anticholinergic drugs. (Dr. Shelly Gray’s research published this year in jama internal medicine, and other articles.)

    I’ve also recently been prescribed propranolol for essential tremor, and have occasionally taken zolpidem for insomnia. Add to that a number of orthopedic surgeries with accompanying rxs for such drugs as meloxicam and gabapentin. I’m in my early 70s and am noticing memory problems. Can you advise as to whether the above medications have anticholinergic activity? thank you so much.

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