Tens of millions of people take SSRI and SNRI-type antidepressants on a daily basis. SSRI stands for selective serotonin reuptake inhibitor. SNRI stands for serotonin and norepinephrine reuptake inhibitor. We know that sounds like medical jargon. Without going too deep into the neuropharmacology, it boils down to how these neurotransmitters are modified in the brain by popular antidepressants. Let’s not forget acetylcholine, another critical neurotransmitter. It too is affected by some antidepressant medications. What is the connection between antidepressant drugs and dementia?
What Antidepressant Drugs Might Be Linked to Memory?
Some of the most dispensed drugs in the pharmacy may be affecting cognitive function. What antidepressants are we referring to: amitriptyline, sertraline, fluoxetine, citalopram, escitalopram, venlafaxine and mirtazapine for starters.
A large analysis from Sweden raises crucial questions about a possible link between such medications and cognitive decline (BMC Medicine, Feb. 25, 2025). Over 18,000 older patients with a diagnosis of dementia were tracked for up to 11 years. The average follow-up was just over 4 years. All were part of the Swedish Registry for Cognitive Dementia Disorders.
The authors found that those taking antidepressants such as sertraline or escitalopram experienced a faster cognitive decline than those not using antidepressants. The higher the dose, the greater the risk for severe dementia, fractures and death. This is important because when pharmacologists see a dose-response curve, it frequently reinforces an association.
I like to describe the dose response relationship as the aspirin effect. If you take 1 coated baby aspirin (81 mg) the chances are pretty good that you won’t experience stomach upset. If you swallow 2 aspirin tablets (650 mg) to ease a headache, you might have a little heartburn, especially if you are sensitive to aspirin. If you swallow 6 tablets all at once (1,950 mg), there is a good change your stomach will complain even if your stomach is tough. The association between aspirin and stomach upset is firmly established because of this dose response curve.
The authors of the Swedish study state:
“In this cohort study, use of antidepressants was associated with faster cognitive decline in patients with dementia, in particular SSRIs (i.e., citalopram, sertraline and escitalopram) and mirtazapine. These effects appeared to be more pronounced in patients with more severe dementia. Compared with sertraline, escitalopram presented faster cognitive decline, while citalopram was linked to a slower cognitive decline. Additionally, higher dispensed doses of SSRIs were associated with greater cognitive decline, as well as increased risks of severe dementia, all-cause mortality, and fracture. Our study cannot distinguish whether these findings are due to the antidepressants or the underlying psychiatric indication.”
The Confusing Connection Between Antidepressant Drugs and Dementia:
We have to be perfectly transparent. Previous research has produced mixed results with regard to cognitive decline. The Swedish researchers point out that different studies have produced conflicting results.
For example:
“Population-based cohort studies have found that antidepressant use was related to no or lower risks of all-cause mortality in patients with dementia, but increased risk of fracture.”
Another study published in GMC Geriatrics (Dec. 8, 2023) involving US data found that older people receiving antidepressants were at higher risk for dementia.
“Our findings suggested that older adults with depression receiving SSRIs/SNRIs were associated with an increased dementia risk compared to those receiving psychotherapy.”
Older Antidepressant Drugs and Dementia:
So far we have been focusing on so-called newer generation antidepressant medications. But older antidepressants such as amitriptyline are still prescribed widely and not just for depression. Amitriptyline is prescribed for fibromyalgia, nerve pain, insomnia and migraines.
Amitriptyline has strong anticholinergic activity. That means it interferes with the crucial neurotransmitter acetylcholine. An article published in BMJ (April 25, 2018) reported these results:
“In this case-control study of older adults in the UK, there was a noticeable association between increasing total anticholinergic burden over the previous 4-20 years and incident dementia diagnosis. However, this dose-response effect was not seen for cumulative use of drugs with an Anticholinergic Cognitive Burden (ACB) score of 1 (possibly anticholinergic), and was only evident for certain classes of anticholinergic drugs. Antidepressants (predominantly amitriptyline, dosulepin, and paroxetine) and urologicals (predominantly oxybutynin and tolterodine) with an ABC score of 3 (definitely anticholinergic) 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:
We have been writing about the dangers of anticholinergic drugs and dementia for more than a decade. There are dozens of studies and hundreds of articles referencing anticholinergic drugs and dementia in the National Library of Medicine database. Despite the preponderance of data supporting this connection, many health professionals and patients are either unaware of this relationship or remain unconvinced that it is a real problem. What is especially worrisome is the dramatic increase in the use of anticholinergic drugs in recent decades. A study in the British Journal of Clinical Pharmacology, Aug. 18, 2021 notes that:
“Anticholinergic burden in the sample increased up to 9-fold over 25 years…”
“The greatest increase was seen in the prescribing of antidepressants.”
Antidepressants are taken by millions of people. Amitriptyline (Elavil), for example, is prescribed to about two million people annually. It is considered old-fashioned, but many doctors now prescribe it for insomnia. Paroxetine (Paxil) is more “modern.” about two million people take it regularly. Both drugs have anticholinergic activity.
Older allergy medicines with sedating antihistamines are also problematic. Millions of people take such drugs either to ease their stuffy noses or fall asleep at night.
As a result, many people are taking a number of anticholinergic drugs simultaneously. A new study in Neurology (online, Sept. 2, 2020) suggests that may hasten cognitive decline. It confirms the results from a study in JAMA Internal Medicine (June 25, 2019). What is the big picture on anticholinergic drugs and dementia?
Brain Fog, Anticholinergic Drugs and Dementia:
This reader shares a story of brain fog associated with anticholinergic drugs:
Q. Several years ago I read your article about anticholinergic drugs. At that time, my husband and I were taking a sedating antihistamine every night for allergies and to help us sleep.
We immediately stopped, and within days noticed a major difference in brain function. All the “fog” cleared; no more “cotton” in the brain. At last, I could recall names and words that often escaped me previously.
My mom died of Alzheimer’s and I feared that I might be in the early stages of early-onset Alzheimer’s. I am grateful to you for providing this very important information.
A. Researchers keep confirming the connection between anticholinergic (AC) drugs and the risk of cognitive impairment (Neurology, online, Sept. 2, 2020). Many people are not aware that medications they take for granted could have anticholinergic activity. Sedating antihistamines, drugs for overactive bladder, some antidepressants and motion sickness medicine are just a few examples of AC drugs.
What is Acetylcholine and Why Is It Important?
Let’s nail down the basics. Acetylcholine (ACh) is a critical neurotransmitter. It can be pronounced a couple of different ways (ASS-se-TEAL-coal-EEN; AS-i-TILE-Koh-LEEN; uh-settle-COAL-lean). This crucial compound is responsible for a great many vital functions. Without ACh we would die in short order. It activates muscles. You could not walk, breathe or pick up a pencil without acetylcholine on board.
Acetylcholine and the Brain:
ACh is also essential to the central nervous system. It plays a critical function for learning and memory. When our cholinergic neurons (that make acetylcholine) become dysfunctional, we end up with memory problems and/or Alzheimer’s disease. The few barely effective drugs that are prescribed for Alzheimer’s are designed to boost the cholinergic nervous system.
Doctors should have realized that acetylcholine was crucial for brain function over 100 years ago. That’s because German obstetricians were intentionally trying to help women forget the pain of childbirth. They administered a cocktail of morphine and the drug scopolamine during labor and delivery. Women had no memory of what happened.
The doctors in Germany called this amnesia experience Dammerschlaf. It meant “twilight sleep.” They described the process as “clouded consciousness with complete forgetfulness.” You might think this would have been a red flag for neuroscientists. Instead, they assumed it was a short lived effect. That may have been true. But there is growing evidence that interfering with ACh over many years with drugs like scopolamine could well lead to cognitive dysfunction.
What Are Anticholinergic Drugs?
Scopolamine is a classic anticholinergic (AC) drug. It interferes with the ability of acetylcholine to reach and activate ACh receptors. Scopolamine is prescribed to prevent the nausea and vomiting of motion sickness (Transderm Scop). Scopolamine diminishes bodily secretions and intestinal contractions. The drug is sometimes given prior to surgery to reduce salivation.
Most health professionals know that scopolamine, and its chemical cousin atropine, are powerful anticholinergic drugs. The drug Lomotil (diphenoxylate plus atropine) is prescribed for people with diarrhea or a diagnosis of IBS (irritable bowel syndrome with diarrhea).
Stealth Anticholinergic Drugs and Dementia:
What many health professionals do not realize is that there are scores of drugs on the market with anticholinergic activity. They include antihistamines such as diphenhydramine, the active ingredient in Benadryl and most over-the-counter PM pain medicines. Health professionals may not realize that some of the drugs they prescribe for anxiety, depression, Parkinson’s disease, overactive bladder or chronic obstructive pulmonary disease have anticholinergic activity.
Researchers have begun speaking about the “anticholinergic burden” patients bear when they take more than one medicine with AC activity (BMC Geriatrics, March 25, 2015).
“The cumulative effect of taking multiple medicines with anticholinergic properties termed as anticholinergic burden can adversely impact cognition, physical function and increase the risk of mortality.”
Research on Anticholinergic Drugs and Dementia:
A study in the journal Neurology (online, Sept. 2, 2020) reports that older people taking at least one anticholinergic drug have an increased risk for developing mild cognitive impairment over the next decade. Those at higher genetic risk for Alzheimer’s disease were at far greater risk from such medications. The senior author cautions her medical colleagues to try to deprescribe such drugs before people begin to develop signs of cognitive impairment.
In last year’s study, British researchers reviewed the medical records of more than 250,000 people in primary care practices in the UK (JAMA Internal Medicine, June 25, 2019). There were nearly 59,000 individuals who had been diagnosed with dementia. Each one was matched to five controls of similar age who had no dementia diagnosis.
In looking back over more than a decade of prescriptions, the investigators found that people who had taken anticholinergic medicines were almost 50 percent more likely to get a dementia diagnosis. Those with greater total exposure had a higher risk. Pharmacologists call this a dose response curve. It is often considered convincing evidence that the effect is real. This also corresponds to other research on this general topic.
The authors conclude:
“Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.
“The present study adds further evidence of potential risks associated with strong anticholinergic drugs, particularly those that are antidepressants, bladder antimuscarinic drugs, antiparkinson drugs, and epilepsy drugs.”
An accompanying editorial notes (JAMA Internal Medicine, June 25, 2019):
“The authors report an association between long-term use of strong anticholinergic medications and the diagnosis of ADRD [Alzheimer disease and related dementias], replicating findings from similar studies from various international populations.”
These scientists also call for “deprescribing trials” that would test whether taking people off anticholinergic drugs would lower their likelihood of developing dementia.
Other Research Linking Anticholinergic Drugs and Dementia:
As we mentioned, this is not the first study to suggest that anticholinergic drugs are associated with Alzheimer’s disease and/or other dementias. Eleven years ago we wrote about Catholic priests and nuns who had cognitive declines associated with anticholinergic drug exposure. You may find this early research of interest.
Some Drugs Dull Mental Edge
A surprising number of drugs can blunt a person’s mental edge, especially in older individuals.
More than three years ago we posed this question:
Are Anticholinergic Drugs Bad for Your Brain?
How Would You Know if You Were Taking Anticholinergic Drugs?
Many health professionals are surprised to learn how many medications they prescribe have anticholinergic activity. Antidepressants like amitriptyline (Elavil) and paroxetine (Paxil) have significant anticholinergic activity. So do medicines for overactive bladder or incontinence such as oxybutynin (Ditropan) and tolterodine (Detrol).
You can learn more about the various drugs with AC activity at this link:
Commonly Prescribed Anticholinergic Drugs Linked to Dementia
Never stop any medicine without checking first with the prescriber. Some drugs with anticholinergic activity cannot be stopped suddenly. Others may be absolutely crucial for a serious health condition like Parkinson’s disease or congestive heart failure. If you are concerned about your anticholinergic “burden,” ask whether a difference medicine could be substituted.
If you would like to see a comprehensive list we have drawn up about anticholinergic drugs and dementia, here is a link:
Where Can I Find A List of Anticholinergic Drugs?
Share your own experience with anticholinergic drugs in the comment section below. If you found this article of value, please share it with friends and family by scrolling to the top of the page and clicking on the icon for email or social media. You can also support our work by signing up for the ad-free option at this link. Thank you for helping us provide breaking health news and in-depth drug information you won’t find anywhere else.
Citations
- Coupland, C. A., et al, "Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study," JAMA Internal Medicine, June 25, 2019, doi:10.1001/jamainternmed.2019.0677
- Campbell, N.L., et al., "Preventing Alzheimer Disease by Deprescribing Anticholinergic Medications," JAMA Internal Medicine, June 25, 2019, doi:10.1001/jamainternmed.2019.0676
- Wang, G.H-M., et al, "Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study," BMC Geriatrics, Dec. 8, 2023, doi: 10.1186/s12877-023-04475-z
- Mo, M., et al, "Antidepressant use and cognitive decline in patients with dementia: a national cohort study," BMC Medicine, Feb. 25, 2025, doi: 10.1186/s12916-025-03851-3
