Anticholinergics are among of the most common types of drug prescribed—with one study estimating that they’re used by 20 to 50 percent of Americans age 65 and older—but research is raising concerns about their safety.
A study published in April 2018 in BMJ of more than 40,000 patients in the UK found that the use of certain types of anticholinergics deployed to treat depression, Parkinson's disease and bladder conditions is associated with an increased risk for dementia.
In particular, the researchers found that people 65 and older who had used anticholinergic anti-Parkinson’s drugs 15 to 20 years earlier had a roughly 29 percent increased risk of developing dementia. Those who took anticholinergics for bladder issues during that timeframe had up to a 27 percent increased risk of dementia, and those who took anticholinergic antidepressants around that time had a roughly 19 percent increased risk of dementia.
Put another way, the study authors noted that while a typical patient aged 65 to 70 would ordinarily expect a 10 percent chance of developing dementia over the next 15 years of their lives, that risk would increase by about two percent after having taken anticholinergic antidepressants.
While it’s not certain that anticholinergic drugs are the cause of dementia, people who took them were more likely to be diagnosed with dementia, and the association was observed to be stronger with more exposure to the drugs.
But given the long timeframe used in the study, the findings may be relevant for adults currently in their 40s and 50s.
What are anticholinergic drugs?
Anticholinergics are used for a variety of conditions, not only depression, Parkinson’s and urinary incontinence, but also gastrointestinal disorders and allergies. Some of them work by preventing the neurotransmitter acetylcholine (also known as the cholinergic system) from sending messages through the nervous system. For other anticholinergic drugs, blocking acetylcholine and suppressing the cholinergic system is an unintended side effect.
Acetylcholine is involved in the production of memory and other aspects of cognition and it’s one of the neurotransmitters that becomes depleted rapidly during the onset of Alzheimer’s disease and related forms of dementia. (Acetylcholine levels also drop, but to a much lesser extent, as a result of natural aging.) It’s worth noting that most drugs used today to treat Alzheimer’s work by increasing the activity of acetylcholine.
It’s known that anticholinergics—in hindering the work of acetylcholine—affect cognition in the short term. Previous research has also linked the use of anticholinergics to cognitive decline, though it’s been unclear whether the link to dementia was a result of the drugs or the underlying condition the drugs had been used to treat.
The April 2018 study strengthens the link between use of anticholinergics and dementia risk.
What is dementia?
Dementia is a general term that describes symptoms associated with a decline in mental ability. The most common cause of dementia in people 65 and older is Alzheimer’s disease, which involves the formation of clumps of protein in the brain that are believed to interfere with the ability of brain cells to communicate with each other. Vascular dementia—the second most common type—results from damage to the vessels that supply blood to the brain, and Lewy body dementia, like Alzheimer’s, involves the buildup or proteins in the brain.
Dementia often entails impaired memory, as well as altered language abilities, confusion and disorientation, difficulty paying attention, hampered judgment, personality changes and problems with motor function. These symptoms tend to start slowly and get worse over time.
In order to diagnose dementia, a doctor will typically analyze a patient’s medical history, perform a physical exam and cognitive and neurological tests and ask the patient and loved ones about changes in cognition, behavior and daily function.
Do anticholinergics increase dementia risk?
Some may, according to the research, but not all do. The study looked at patients’ exposures to anticholinergics four to 20 years before a diagnosis of dementia and found an increased risk of dementia only for certain classes of anticholinergic drugs.
The antidepressants implicated in the study as having anticholinergic effects were tricyclic antidepressants (such as amitriptyline) and one specific kind of selective serotonin-reuptake inhibitor (SSRI), paroxetine. Other SSRIs (such as citalopram, venlafaxine, sertraline and duloxetine) were not observed to have anticholinergic properties.
The study also found a link between dementia and anticholinergic drugs used to treat bladder problems, namely, oxybutynin and tolterodine, and some Parkinson’s medications, such as procyclidine.
Anticholinergic gastrointestinal and cardiovascular drugs were not associated with increased dementia risk.
What about antihistamines?
Antihistamines are a special case. The study only found a small association between some types of anticholinergic antihistamines and dementia, but the link was not considered statistically significant. The problem is that the study only looked at prescription medications and thus may have underestimated the use of antihistamines, since these drugs are typically purchased over the counter.
In previous research, one common OTC antihistamine, diphenhydramine, has been observed to have anticholinergic properties. “Looking at the big picture of the studies I’ve conducted in this area, I’d say that antihistamines with anticholinergic properties, such as diphenhydramine, pose concerns as a risk factor for Alzheimer’s disease,” says study co-author Malaz Boustani, MD, a researcher at the Indiana University Center for Aging Research.
Newer generation antihistamines such as cetirizine or fexofenadine, Dr. Boustani notes, have only possible anticholinergic properties, and are thus less a cause for concern.
If I’m taking an anticholinergic, should I stop?
Prescribing guidelines say that patients who already have dementia should not take anticholinergics. The study authors also note that anticholinergic drugs should be avoided when treating patients with Parkinson’s, since the disease is related to an elevated risk of dementia. Patients taking anticholinergics to treat other conditions such as depression or bladder problems should check with their healthcare providers.
"My suggestion is: Anytime your doctor gives you medicine, first ask, ‘What are the potential adverse effects of this medicine on my brain health?’” says Boustani. “Demand time with your doctor to explain to you the risks and benefits of anticholinergics, including over-the-counter drugs. If your doctor doesn’t have that time, find a doctor that does.”
While you shouldn’t abruptly stop taking drugs you need without checking with your healthcare provider, there may be alternatives to anticholinergics for your condition. For example, SSRIs other than paroxetine may be smart alternatives to tricyclic antidepressants for people with depression, and both people with depression and bladder control issues may benefit from non-drug treatments such as cognitive behavioral therapy.
“There aren’t many risk factors for Alzheimer’s disease that are easy to modify,” says Boustani. “For example, it can be hard to change your diet and exercise habits, but it can be relatively easy to stop taking anticholinergic medications.”
Boustani’s recommendation? “If you already have risk factors, such as a first-degree relative with Alzheimer’s disease, don’t tip it over by taking anticholinergics.”
