The People's Perspective on Medicine

Commonly Prescribed Anticholinergic Drugs Linked to Dementia

A very large study from the UK has reinforced a link between anticholinergic drugs are dementia. Which drugs are most problematic? Might you be taking anticholinergic drugs without realizing it?
An elderly woman with a tableful of medications looking overwhelmed and confused

Alzheimer’s disease is scary. It robs people of their memories and their ability to function. Many people think it’s brought on by bad genes or bad luck. But there is mounting evidence that our environment also plays a key role in the development of dementia. Over the last decade there is growing recognition that a class of medications known as anticholinergic drugs could be contributing to cognitive decline or even dementia. A new study from the UK reinforces this concern (BMJ April 25, 2018).

Anticholinergic Drugs Block a Key Brain Chemical:

Acetylcholine (pronounced ASS-se-TEEL-kol-EEN) is a neurotransmitter that plays a critical role in brain function. People with Alzheimer disease make less of this important brain chemical. Doctors suspect that medications that interfere with the function of acetylcholine, known as anticholinergic drugs, may cause cognitive impairment.

Learn about the history of anticholinergic drugs, brain fog and “twilight sleep” at this link:

New Research Adds Fuel to the Fire:

Now a large study of people in the United Kingdom has confirmed that some types of anticholinergic drugs can lead to dementia after a few decades. Researchers examined health records from primary care practices throughout the UK.

More than 40,000 people between 65 and 99 were diagnosed with dementia at some point between April 2006 and July 2015. They were matched to 284,000 control subjects of comparable age and sex, but without dementia. This is one of the largest anticholinergic drug studies to date. Over 27 million prescriptions were analyzed over the course of the research.

Investigators reviewed prescriptions for drugs with anticholinergic activity. They found that people taking an anticholinergic medicines were 10 percent more likely to develop dementia in the ensuing years.

In absolute terms, a 65 year-old-person has about twelve chances in one hundred of developing dementia by age 80 if she takes an anticholinergic prescription. The researchers found a dose-response effect, with more anticholinergic medicines linked to a higher chance of a dementia diagnosis.

Which Anticholinergic Drugs Were Worrisome?

Many of the people who developed dementia had taken drugs to treat depression, Parkinson’s disease or overactive bladder. The scientists conclude that there is:

“a robust association between some classes of anticholinergic drugs and future dementia incidence.”

Antidepressants: A Clear Association

Two specific antidepressant drugs stood out in the UK Study. Amitriptyline (Elavil) and paroxetine (Paxil) have substantial anticholinergic activity. The use of strong anticholinergic antidepressants was associated with a 30% increased risk of dementia in future years.

According to our calculations, roughly 10 million amitriptyline prescriptions have been dispensed each year over the last decade. Paroxetine averages around 15 million prescriptions per year. Millions of people take such drugs every day.

Amitriptyline is often prescribed for things other than depression. Many people take it for neuropathy or nerve pain, migraine headaches, fibromyalgia and insomnia. Paroxetine is prescribed for depression, OCD, panic, social anxiety disorder, PTSD, premenstrual dysphoric disorder and the hot flashes of menopause.

Stopping either of these drugs suddenly can produce what is called discontinuation syndrome. That’s a sanitized description of very unpleasant withdrawal symptoms. They can include dizziness, diarrhea, nausea, brain fog, brain zaps, irritability, anxiety, insomnia, sweating and fatigue. Such reactions upon stopping these anticholinergic drugs makes it hard to quit.

No one should ever stop an antidepressant suddenly. This process should always be under medical supervision. Gradual tapering may take months to accomplish if it is decided that the concerns of dementia are worrisome enough to discontinue such drugs.

Antidepressant Withdrawal Feels Like Circles of Hell

Overactive Bladder Drugs:

Two other anticholinergic drugs were found to be associated with the development of dementia over time. They were oxybutynin (Ditropan) and tolterodine (Detrol). The authors concluded that both the antidepressants mentioned above and overactive bladder drugs were:

“consistently associated with incident dementia. These relations were seen even for exposures 15-20 years before the diagnosis of dementia, suggesting that reverse causation or confounding with early dementia symptoms are less likely explanations for the effect.”

Anticholinergic Drugs and Dementia | The Editorial

Health professionals commenting on the new UK study are quick to caution patients not to stop any medications that might have anticholinergic activity. We agree that this research requires thoughtful communication between patients and prescribers. But an editorial in the same issue of the BMJ (April, 25, 2018) asks the question: “Should we be concerned?”

The authors point out that anticholinergic drugs are taken by 10-27% of older adults.

“It is well established that these drugs can cause temporary short term impairment in cognition, including attention and reaction time. Over the past decade, however, mounting evidence suggests that overall use of anticholinergics might be associated with an increased risk of dementia.”

They conclude their editorial with this recommendation:

“In the meantime, what should clinicians do until studies are conducted to further elucidate the underlying biological mechanisms and determine the risk of dementia with specific classes, including over-the-counter anticholinergic antihistamine use not captured by this or previous studies? As suggested by guidelines, anticholinergics in general should be avoided in older adults. Specifically, for most highly anticholinergic drugs, non-pharmacological and pharmacological alternatives are available and should be considered.”

People’s Pharmacy Perspective:

There will be situations when anticholinergic drugs may not be avoided. In such situations it is important for the patient, the family and the physician to weigh the benefits and the risks of a large anticholineric drug burden on the long-term health of the patient.

To help with that conversation we include a link to a list of anticholinergic drugs:

Share your own thoughts on anticholinergic drugs in the comment section below.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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I have been taking Paroxetine (Paxil) for many years for mild depression, and I asked to have my prescription doubled from 20 mg to 40 mg when thoughts of suicide became frequent. The medicine keeps this under control, but this article worries me. I’m 77 and in good health. Suggestions?

This large study confirms that some anticholinergic drugs can raise the risk of dementia — but it should also put minds at ease as there appears to be no dementia risk with anticholinergic drugs used to treat common conditions like hay fever, travel sickness, and stomach cramps,” said Doug Brown, MD, of the Alzheimer’s Society in London.

What low dosage of amitriptyline might be considered safe in regards to memory loss?

I can’t think of a single drug — either Rx or OTC — that I didn’t assume was safe and later heard scary, if not horrible, things about. My policy now is to put NOTHING in my mouth except quality food. Oh yeah, and a designer beer or 2. Perhaps one Tylenol if I’ve gone berserk gardening or skiing. That’s it.

I took a tri-cyclic antidepressant for twenty years to help me sleep. It definately made my memory worse. I have been off of it for perhaps 8 years, but my memory continues to get worse. I will probably have real dementia in a year or two.
Dee

Thank you, Peoples Pharmacy, for publishing this list of drugs. I was belittling my neighbor who took Benadryl for years and now has dementia; and, lo and behold, I am taking a number of meds on the list. All the OTC drugs that I was taking on the list will be substituted with home remedies such as honey and lemon juice. I will continue taking the prescribed drugs. Thank you again.

Both my mother and mother-in-law were diagnosed with Alzheimer’s, Mom age 76, m-i-l 72. They lived very different lifestyles, Mom dealt with severe anxiety and depression, m-i-l a happy go lucky, very active and vivacious health nut. The only common denominator they share is they both took Benadryl to sleep. Their “doctors” advised this! Recently an older friend at church said her doctor had advised her to do the same. I cautioned her! Of course, our mothers could have had Alzheimer’s anyway. I do believe Benadryl exacerbated in tendency. We must be our own health care advocates and advocate for our elderly loved ones as well.

Several years ago I had surgery for stress incontinence, but the only solution for urge incontinence was an anticolinergic, so I took Oxybutynin, which seemed to work. But within the past two or three years I started reading about the possible dementia connection, so I quit taking them and told my doctor why, altho she expressed some skepticism. I think my brain is sill OK because I can still do the Sunday crosswords and haven’t noticed any problems. I’m 84, and just visit the bathroom more often. as a precaution, and use panty liners just in case.

I wonder whether this is a chicken/egg issue. Perhaps, in the very early stages of dementia, people are depressed, anxious, nervous, can’t sleep, etc. and are put on these types of drugs.

I think I’m going to try to drop my evening 50mg of diphenydramine. I’ve lessened down to 1/80mg Propanol. Is propanolol anticholinergic?

I am very sensitive to anticholinergics and try to stay away as much as possible. I have the list you printed years ago as well as the article on which it was based on my laptop’s desktop. I had a list of drugs that I knew made me crazy but your article gave me the connection I sought; they were all anticholinergics. My mother has been gone for 10 years. To this day I believe a sudden onset of dementia (not alzheimer’s) was due to Ditropan. I am shocked when I hear seniors say that their MD told them to take benadryl and would wear a diaper before I took an overactive bladder drug. Thanks for continuing to highlight this dangerous situation.

Even though it is said that the cause of overactive bladder condition is low levels of estrogen, given that they are purported to help ‘relax’ the bladder, wouldn’t the so-often discussed gin-soaked raisins help to alleviate overactive bladder? Has anyone tried this?

Someone commented that doxylamine succinate is not listed as having anticholinergic effects, but she needs to look again or simply search on line asking. It certainly does have strong effects according to one source I found. I believe also that it is on one of these lists in some form such as Unisom.

Doxylamine succinate most certainly does have anticholinergic effects. I stupidly took it daily for sleep (even though the label tells you it’s not for extended use) for about 6 years. The two best words to describe the way I felt in the 5th and 6th year was “cognitive decline”. It wasn’t until I saw the big report in the news that I put it all together. I’m 47 and have memory issues that scare me for the future. Yikes.

Stay away from anticholinergics.

I understand the probable cognitive effects of anticholinergic drugs, and I appreciate your work to make us more aware. I do take exception to your confusing uses of the terms “Alzheimer’s”, “dementia” and “memory problems.” My understanding is that Alzheimer’s is a specific disease with effects well beyond the cognitive ones, even though those are the most obvious ones. While cognitive decline is indeed serious and frightening, it may well not be Alzheimer’s. I hear people regularly say Alzheimer’s when they mean unspecified dementia. Please use these terms clearly and distinctly.

My wife took Ditropan for many years and was diagnosed with Dementia when she was 72. Her Urologist did not know the facts about Ditropan and older people. I had to tell her I wanted her prescription changed to another class of drug

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