Antihistamines, MCAS and Dementia Risk
Should I Be Worried About Taking Antihistamines Long Term?
Antihistamines can be extremely useful for people with allergies, hay fever, hives and Mast Cell Activation Syndrome (MCAS).
Many people with MCAS need antihistamines more regularly than someone who simply takes an occasional tablet during hay-fever season. This can understandably raise concerns when headlines suggest that antihistamines may be linked with dementia.
The important point is that not all antihistamines are the same.
The main concern has traditionally been with older, sedating antihistamines that have anticholinergic effects, particularly when they are taken regularly over long periods.
Newer, non-sedating antihistamines have much less effect on the brain, and recent evidence is reassuring.
What Does "Anticholinergic" Mean?
Acetylcholine is an important chemical messenger in the brain. It is involved in:
memory
learning
attention
concentration
normal brain function
Some medications block acetylcholine. These are called anticholinergic medicines.
Strong anticholinergic medicines can cause:
dry mouth
constipation
blurred vision
difficulty passing urine
drowsiness
confusion
memory and concentration problems
These effects become particularly important as we get older.
Researchers have therefore questioned whether taking strongly anticholinergic medicines for many years could contribute to dementia risk.
Which Antihistamines Are We Most Concerned About?
Older, Sedating Antihistamines
These antihistamines enter the brain much more readily and generally have stronger sedating and anticholinergic effects.
Examples include:
Promethazine – Phenergan
Diphenhydramine
Doxylamine – Restavit and some sleep preparations
Dexchlorpheniramine – Polaramine
Chlorpheniramine / chlorphenamine
These are sometimes referred to as first-generation antihistamines.
They can be very effective, but they should not be taken every day indefinitely.
The concern is particularly relevant in older adults and in people taking several other medications with anticholinergic effects.
What About the Newer Antihistamines?
Newer or second-generation antihistamines include:
Fexofenadine – Telfast
Loratadine – Claratyne
Desloratadine – Aerius
Cetirizine – Zyrtec
Bilastine – Bilaxten
These generally have much less anticholinergic and sedating activity and enter the brain far less readily than older antihistamines.
Cetirizine can still cause some sleepiness in some people, but it is still considered a newer-generation antihistamine.
For someone who needs regular antihistamine treatment, including many people with MCAS, these are generally preferable to routinely using older sedating antihistamines.
What Does the Research Actually Show?
There have been studies linking long-term exposure to medications with strong anticholinergic effects with an increased risk of dementia.
One large study found that people with the greatest cumulative exposure to strong anticholinergic medications had approximately a 50% higher relative risk of dementia compared with people who did not use them.
Importantly, this was an observational study.
That means it found an association. It did not prove that the medications caused dementia.
Other factors may partly explain the association.
For example, people requiring these medicines may have other medical conditions, inflammation, poor sleep or symptoms that themselves influence dementia risk.
What About Antihistamines Specifically?
A large 2024 study looked at people with allergic rhinitis.
It found that increasing cumulative exposure to antihistamines was associated with increasing dementia diagnoses. The association was strongest with older first-generation antihistamines, although a smaller association was also reported with second-generation antihistamines.
Again, this did not establish that antihistamines caused dementia.
This is particularly important because people who need frequent antihistamines may have more severe allergic or inflammatory disease in the first place.
More recent research published in 2026 has been reassuring.
A large study examining people aged 50 and over with allergic rhinitis, chronic sinusitis or chronic urticaria found no increased dementia risk associated with second-generation antihistamine use.
So, at present, there is no convincing evidence that taking a modern second-generation antihistamine causes dementia.
What Does This Mean If You Have MCAS?
This is particularly important for people with MCAS because antihistamines may form an important part of treatment.
The answer is not to stop your antihistamines because you are frightened of dementia.
Instead, we consider which antihistamine you are taking and why you need it.
For regular or longer-term treatment, we generally favour newer, less-sedating antihistamines such as:
Fexofenadine
Loratadine
Desloratadine
Cetirizine
Bilastine
Older sedating antihistamines can still have a place. For example, they may occasionally be useful during a significant flare when itching, hives or other symptoms are difficult to control.
The issue is different when someone is taking a strongly sedating antihistamine every night for months and months or years, particularly simply to help them sleep.
A Simple Way to Think About It
🟢 Generally preferred for regular use
FexofenadineLoratadineDesloratadineBilastineCetirizine
These are newer-generation antihistamines with much less anticholinergic activity.
🟠 Use more thoughtfully, particularly long term
PromethazineDiphenhydramineDoxylamineDexchlorpheniramineChlorpheniramine
These are older, sedating antihistamines with greater effects on the brain and varying degrees of anticholinergic activity.
They are not necessarily "bad" medicines. The question is how often, how much and for how long they are being used.
Don't Forget the Total Anticholinergic Load
Antihistamines are not the only medicines with anticholinergic effects.
Some medications used for:
bladder problems
depression
nausea
Parkinson's disease
sleep
pain
mental health conditions
can also contribute.
Therefore, someone taking several medications may have a much greater total anticholinergic burden than someone taking one medication occasionally.
This becomes increasingly important as we get older.
What About Taking an Antihistamine Occasionally?
There is no good evidence that occasionally taking a modern antihistamine causes dementia.
Even with older antihistamines, the concern in the research relates much more to repeated cumulative exposure over long periods, rather than taking an occasional tablet when it is genuinely needed.
My Practical Approach for MCAS
If antihistamines are helping control MCAS symptoms, there is usually no reason to suddenly stop them.
Where possible:
Use a newer, less-sedating antihistamine for regular treatment.
Avoid relying on sedating antihistamines every night simply for sleep.
Use the lowest effective treatment that keeps symptoms controlled.
Once MCAS is stable, review whether the same amount of medication is still required.
Work on identifying and reducing the triggers driving mast-cell activation rather than relying entirely on medication.
If you take several medications, ask your doctor or pharmacist to review your overall anticholinergic medication burden.
For some people with significant MCAS, the benefits of controlling mast-cell symptoms, inflammation, itching, palpitations and disrupted sleep may considerably outweigh the theoretical or uncertain long-term risks of treatment.
Treatment therefore needs to be individualised.
The Bottom Line
Antihistamine does not automatically mean dementia risk.
The strongest concern has been around older, sedating and strongly anticholinergic medications used repeatedly over long periods.
Modern second-generation antihistamines have far less effect on the brain, and recent large-scale evidence has not shown an increased dementia risk with their use.
For people with MCAS who require ongoing antihistamines, newer non-sedating antihistamines are generally the more appropriate long-term option.
Do not stop a medication that is controlling significant symptoms because of a frightening headline. Instead, review which antihistamine you are taking, how often you need it and whether there is a lower-anticholinergic alternative.
Important Information
This leaflet provides general educational information only and should not replace personalised medical advice. Do not stop or change prescribed medication without discussing this with your doctor or pharmacist.
References
Gray SL, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Internal Medicine. 2015. This study demonstrated a cumulative dose-response association between strong anticholinergic exposure and dementia.
Su CH, et al. Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis. Journal of Allergy and Clinical Immunology: In Practice. 2024;12:2155-2165. The observational study reported associations for both generations of antihistamines, stronger with first-generation medicines, but could not establish causation.
Olbrich H, et al. Second-Generation H1-Antihistamines Do Not Alter Dementia Risk in Type 2 Inflammatory Diseases: A Target Trial Emulation Using Real-World Data. Journal of Allergy and Clinical Immunology: In Practice. 2026. This large study found no increased dementia risk associated with second-generation antihistamines.
Healthdirect Australia. Antihistamines. Australian guidance lists fexofenadine, loratadine, desloratadine, bilastine and cetirizine as less/non-sedating antihistamines, while dexchlorpheniramine, diphenhydramine, doxylamine and promethazine are sedating antihistamines.
By Dr Purity Carr
GP
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