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Can Benadryl and other anticholinergic drugs give you dementia?
Dementia has become a national health care crisis. This Disease affects not only patients but also families and caregivers. Early signs of dementia include difficulty writing and speaking, misplacing items, confusion, frustration, and memory loss.
Brain failure is an easy way to describe this Disease.
Alzheimer’s Disease, the most common form of dementia, progresses very slowly. Other types, such as vascular dementia may strike immediately after a stroke. Unfortunately, we are all just one stroke away from becoming a potential dementia patient.
Dementia patients will eventually depend on others for their complete care.
For More Information On Lewy Body Dementia, See My Previous Post By Clicking The Box Below:
What is an anticholinergic drug?
An anticholinergic drug is one that blocks acetylcholine. Acetylcholine is one of the neurotransmitters located in the brain and other parts of the body.
It is quickly destroyed by an enzyme called acetylcholinesterase and has a very short duration of action.
Acetylcholine has many functions:
- Decreases heart rate, acts as a vasodilator, decreases heart muscle contraction.
- Causes urinary smooth muscle contraction of the bladder.
- Helps move food through the digestive tract by increasing peristalsis.
- Stimulates gland secretion.
- Causes bronchoconstriction in the lungs.
- Effects memory and learning
There is no single scale available to rate medications for anticholinergic burden.
More than 600 medications have various levels of anticholinergic effects.1
In my practice, I primarily use the Beers List and two research articles to get this information.
I will list a few examples in each category below. Please reference the following articles if you require an extensive list of agents:
The two articles I utilize currently are:
- Mohammed Saji Salahudeen, Stephen B Duffull & Prasad S Nishtala.Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systemic review. BMC Geriatrics volume 15, Article number: 31 (2015)
2. Durán C, Azermai M, Vander Stichele R. Systematic review of anticholinergic risk scales in older adults. European Journal of Clinical Pharmacology. 2013;69(7):1485-1496. doi:10.1007/s00228-013-1499-3.
Anticholinergic medications are used for a variety of indications. Some of these are listed below:
First-generation antihistamines have a high level of anticholinergic activity.
Diphenhydramine (Benadryl) is the most common. This drug is used in its injectable form in hospitals to treat acute allergic reactions along with epinephrine.
It is also used for seasonal allergies, motion sickness, Parkinson’s Disease, and as a sleep aid.
Diphenhydramine is available over the counter (OTC). Benadryl and memory loss has become a recent study subject.
I tell my patients to steer clear of any OTC medications that end with “PM.”
Most of these products contain diphenhydramine in combination with a pain reliever.
Diphenhydramine is a poor choice to help elderly patients sleep.
Like all anticholinergics, it may lead to blurred vision, dry mouth, and an increased risk of falls.
Antihistamines with high anticholinergic activity:
- Diphenhydramine (Benadryl)
- Dimenhydrinate (Dramamine)
- Cyproheptadine (Periactin)
- Hydroxyzine (Atarax, Vistaril)
Antidepressants are primarily used to treat depression and anxiety disorders.
Some antidepressants also possess anticholinergic properties. This is especially true of the older tricyclic antidepressants.
These are rarely used at high doses currently as SSRI’s, such as sertraline (Zoloft) are much safer and have fewer side effects.
Paroxetine (Paxil) is an SSRI that has a higher anticholinergic burden.
It is best to avoid paroxetine in elderly patients.
Antidepressants with high anticholinergic activity:
- Amitriptyline (Elavil)·
- Clomipramine (Anafranil)
- Desipramine (Norpramin)
- Desipramine (Norpramin)
- Doxepin (Sinequan)
- Imipramine (Tofranil)
- Nortriptyline (Pamelor)
- Paroxetine (Paxil)
All antipsychotics have some anticholinergic activity. Unfortunately, they are the most effective agents we have for the behavioral and psychological symptoms of dementia, so they are often used in this population.
As with the antidepressants, different agents have various levels of anticholinergic activity. Clozapine (Clozaril) and olanzapine (Zyprexa) are the most anticholinergic atypical antipsychotic agents.
Antipsychotics with high anticholinergic activity:
- Chlorpromazine (Thorazine)
- Clozapine (Clozaril)
- Fluphenazine (Prolixin)
- Thioridazine (Mellaril)
Urinary antispasmodics are indicated for overactive bladder symptoms. The most common is oxybutynin (Ditropan). I have personally witnessed these being used in patients who were incontinent. I believe these drugs should be avoided when possible. These medications should not be used in patients with dementia or delirium. The risk in these cases is likely much higher than the benefit.
Drugs such as dicyclomine are used for irritable bowel syndrome. Many dementia patients are incontinent of bowel as well as urine. These medications should be avoided in this population.
Anticholinergic medications for combating antipsychotic side effects
Benztropine (Cogentin) and trihexyphenidyl (Artane) are used to combat dystonia or pseudo-parkinsonism from antipsychotics. This is a case where benefit outweighs risk. These side effects can be debilitating and controlling them is a priority.
Cyclobenzaprine (Flexeril) and methocarbamol (Robaxin) are used to help with pain and muscle relaxation.
Again, these medications are often necessary for patient comfort. I suggest using the agent with the lowest anticholinergic burden possible.
Unwanted Side Effects Caused By Anticholinergic Drugs
- blurred vision
- dry mouth and eyes
- urinary retention
- Increased risk of falls
Treatment Of Anticholinergic Side Effects
- Exercise to help relieve constipation.
- Sugarless candy or gum for dry mouth.
- Increasing fluid intake for constipation and dry mouth.
- Saliva substitutes, mouthwashes or fluoride rinses for dry mouth.
Effects Of Aging
As we age, our bodies react differently to medications.
Our liver and kidneys are not as efficient, and we are composed of more fat and less muscle.
We have less protein circulating in our bloodstreams to bind to medications.
We do not excrete drugs as well as a younger person.
All of these factors lead to an increased effect from the medications we ingest.
Dementia patients also have lower acetylcholine levels.2
Anticholinergic medications block a portion of the remaining acetylcholine leading to a further decrease in cognition.
Clinical Studies On Anticholinergics And Dementia
A clinical review of twenty-seven studies, published in 2009, found all but two discovered an association between the anticholinergic burden of medications and either dementia, delirium, or cognitive impairment.9
A study of 1473 individuals without dementia was conducted over a six-year period to determine whether anticholinergic drugs had an effect on memory decline.
The subjects in this study were between the ages of sixty to ninety years. Several aspects of cognition were measured.
Even though only 2% of the subjects used anticholinergic drugs (n=29), the results indicate these medications may lead to a more rapid cognitive decline in older adults without dementia. 10
The final study I would like to discuss was the subject of our journal club luncheon last week.
This is a new nested case-control study of 58,769 dementia patients and 225,574 controls.
These patients were from England, and data was obtained via the QResearch primary care database.
The purpose of this study was to determine the association between cumulative anticholinergic drug exposure and the risk of dementia.
This study found an increased risk of dementia in patients who used the following types of anticholinergic agents:
- Bladder antimuscarinics
- Anti-epileptic drugs
We were surprised to discover they found no significant increase in dementia risk for:
- Gastrointestinal antispasmodics
- Antimuscarinic bronchodilators
- Skeletal muscle relaxants
Our journal club group consisting of three psychiatrists, a psychiatric nurse manager and myself. We discussed the reason for antihistamines not causing a significant increase in dementia risk.
As a group, we came up with the following possible explanations:
The information obtained was from drugs dispensed. There is no way to determine if the patients ingested the medications.
Patients may not take antihistamines on a consistent basis. Many times they are only utilized for seasonal allergies or to help with insomnia.
Diphenhydramine is available over-the-counter and may not be included in the data obtained by the investigators.
The study also found the link between anticholinergics and dementia was stronger before the age of 80 and in those with vascular dementia as opposed to Alzheimer’s disease.
The increased risk of vascular dementia could be attributed to the anticholinergic agents increasing stroke risk.
We know that antipsychotics increase the risk of heart disease and stroke as well as diabetes.
I want to point out that this study only looked at medications on the Beers list.
This list is created by The American Geriatrics Society and lists drugs that should be avoided if possible in geriatric patients.
There are several medications that we often use which are not on this list. Almost all of the antidepressants, with the exception of paroxetine, are rarely used first line.
Several antipsychotics are also not included. This will undoubtedly affect the study results.
The researchers concluded that there was an almost 50% increase in dementia risk in those who took an equivalent of one single strong anticholinergic medication daily for a three year period.
This leads us to the recommendation that anticholinergic drugs should be avoided when possible, especially in middle-aged and older individuals.
Physicians and pharmacists should look for alternative agents that have fewer anticholinergic side effects in this patient population.11
I practice as a Clinical Pharmacy Specialist on a psychiatric unit which cares for dementia patients.
As a pharmacist on the unit, one of the first tasks I set out to achieve is to minimize the anticholinergic load of the patient.
I have noticed many patients taking anticholinergic medications unnecessarily.
My suggestion is always to eliminate any medications that are not critical to the patient’s health. This applies to all agents, not only anticholinergics.
There are times when anticholinergic drugs must be used. We can employ the strategies described above to reduce the side effects caused by these agents.
There appears to be an increased risk of developing dementia when taking these medications for an extended period of time.
My recommendation is to use anticholinergic drugs only when clearly indicated.
This applies to all individuals, regardless of age.
Sleep aids and allergy medications should only be used when symptoms are present. This also increases the effectiveness of the agents. The body can become tolerant, especially to sleep aids if used chronically.
The main lesson here is to minimize the use of medications possessing anticholinergic properties.
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Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. Published online June 24, 2019179(8):1084–1093. doi:10.1001/jamainternmed.2019.0677.