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:
“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.”
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.
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:
“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.”
“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.
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:
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