Anticholinergic Burden: Why Many Medicines Together Cause Confusion

It is rarely one medicine that leaves someone confused, forgetful and unsteady on their feet. It is the sum of many preparations, each of which counts as harmless on its own — something for allergies, a sleeping tablet, something for the bladder, something for nausea. Specialists call this the anticholinergic burden. It is one of the most frequently overlooked problems in modern medicine — and one of the few cases in which confusion in old age can recede again.

1. What "anticholinergic burden" means

Anticholinergic means: a substance blocks the docking sites for the messenger acetylcholine. With some medicines that is the intended main effect — with a preparation for an overactive bladder, for example. With a great many others it is a side effect that nobody needs and that is barely noticeable on its own.

The term anticholinergic burden (in German anticholinerge Last) describes the total sum of these effects across all the preparations someone takes. And that is exactly where the core message of this article lies:

Making matters worse, some of these preparations are available over the counter. They appear on no medication plan, are not mentioned at the practice and are not recorded in hospital. Anyone who wants to add up the burden therefore has to start with the complete medication list, not with the pile of prescriptions.

2. What acetylcholine does in the body

Once you understand where acetylcholine works, you can derive the symptoms for yourself instead of learning them by heart. The messenger is particularly important in five places:^¹

• In the brain: it is central to memory, attention and learning. Block it, and those are exactly what suffer.
• In the salivary glands: it controls the flow of saliva.
• In the gut: it drives bowel movement.
• In the bladder: it makes the bladder muscle contract so that the bladder can empty.
• In the eye: it narrows the pupil and focuses the lens for close vision.

If these docking sites are blocked, a remarkably predictable series of complaints follows — though in everyday life it is rarely dramatic, more a matter of creeping change.

3. The typical chain of symptoms

This table connects the sites of action with what you actually notice:

What stands out is how unspecific all of this is. Every single symptom can be explained in another way as well: dry mouth as a sign of ageing, constipation as a lack of exercise, forgetfulness as early dementia. The decisive clue is therefore not the individual symptom but the pattern — when several of these complaints appear at the same time, and appear after a change of medication.

4. Which drug groups act anticholinergically

The list that follows is not complete — anticholinergic effects are found in many drug classes. It names the groups most often involved in everyday practice.^²

Older antihistamines

The first-generation antihistamines — diphenhydramine, doxylamine or dimetindene, for instance — have a marked anticholinergic action and are sedating on top of that. That is precisely why some of them are found in over-the-counter sleeping aids and cold remedy combinations. This is probably the most common blind spot of all: anyone taking a "harmless" sleeping tablet from the chemist in the evening is raising their anticholinergic burden considerably.

Modern second-generation antihistamines such as cetirizine or loratadine barely enter the brain and are considered far more favourable in this respect. With hay fever and hives, switching is often the easiest gain available.

Tricyclic antidepressants

Amitriptyline and related substances such as doxepin or clomipramine are among the more strongly anticholinergic medicines. Today they are frequently used not for depression but in low doses for chronic pain, migraine or sleep problems — and the anticholinergic effect remains just the same.

Preparations for an overactive bladder

Here the anticholinergic action is expressly wanted: substances such as oxybutynin, tolterodine or solifenacin damp down the bladder muscle in overactive bladder. The price is that they block the same receptors in the gut, in the eye and, depending on the substance, in the brain. There are alternatives that work by a different principle — a good topic for your next appointment.

Parkinson's medicines

Classic anticholinergics such as biperiden are used in Parkinson's and for certain side effects of antipsychotics. In older people they are prescribed cautiously today, because the risk of confusion is high.

Antipsychotics

Antipsychotics differ widely. Some are barely anticholinergic, others markedly so — quetiapine, olanzapine and clozapine are among the more relevant ones. It becomes problematic when such a medicine is given in a low dose "just to help with sleep" or for agitation in dementia — because then it reaches precisely the people who are most sensitive.

Preparations for nausea and travel sickness

Dimenhydrinate and scopolamine have a pronounced anticholinergic action and are in part available without prescription. Metoclopramide works through a different mechanism but is likewise one of the centrally acting preparations that should be used with care and for a limited time in older people.

Antispasmodics for the stomach and bowel

Butylscopolamine for abdominal cramps barely enters the brain and is less problematic centrally — but it can worsen dry mouth, visual disturbances and difficulty emptying the bladder. The same applies to some preparations used in irritable bowel syndrome. On top of these come groups with weaker effects: certain medicines for heart rhythm disturbances, individual muscle relaxants, some preparations for dizziness. Inhaled anticholinergics used in COPD formally belong here too, but act predominantly locally in the lungs.

5. Why the sum is what counts — a worked example

Picture a typical case: a 78-year-old woman who is managing well. She takes a low-dose tricyclic antidepressant for back pain, a bladder preparation for urge incontinence, an over-the-counter sleeping aid with an older antihistamine in the evening and something for nausea when she needs it.

Each of these prescriptions makes sense on its own, and none is a treatment error. But all four pull in the same direction — and in all likelihood no single prescriber has ever seen them together. That is exactly how anticholinergic burden arises: not through one wrong decision, but through many right decisions without an overall view.

In old age two amplifiers are added: elimination through the kidneys and liver becomes slower, and the protective barrier between blood and brain becomes more permeable. Both increase the effect at the same dose — more on this under Medications in old age.

6. Confusion in old age: the misreading with the gravest consequences

This is the heart of this article. When an older person becomes forgetful, slow, unable to concentrate and at times confused within a matter of weeks, one explanation suggests itself to relatives: it is starting. Dementia.

Sometimes that is right. Sometimes, though, it is a medication-induced cognitive impairment — and that is in principle capable of receding, once the preparations responsible are identified and adjusted by a doctor. This is precisely where the difference lies between a diagnosis that stays and a state that can disappear again.^³

There are pointers that speak for a medication-related cause:

• A connection in time — the change began days to weeks after a new medicine, a dose increase or a hospital stay.
• A rapid onset — dementia usually develops over months to years, not within a fortnight.
• A fluctuating course — clear in the morning, muddled in the evening; good days and bad days in alternation.
• Physical signs alongside — dry mouth, constipation, blurred vision and bladder problems appear together with the confusion.

7. Risk of falls: the quiet chain of consequences

The cognitive effects get most of the attention, but the physical ones carry at least as much weight. Blurred vision, light-headedness, slowed reactions and swings in blood pressure add up to an increased risk of falling — and in advanced age a fall with a fractured hip often changes more than the original illness did. The chain runs quietly: one preparation makes you drowsy, a second lowers your blood pressure, a third worsens your close vision. Nobody falls because of a single preparation — people fall because of the combination. What plays a part in this is explained in the guide Dizziness from medications.

8. The PRISCUS list and other tools

You do not have to work out the assessment yourself — established aids exist. The best known in Germany is the PRISCUS list: a German overview compiled by specialists of substances regarded as potentially unsuitable for older people, each with a rationale and with suggested alternatives. Many strongly anticholinergic substances appear on it.^⁴

Alongside it there are international rating scales that assign every substance a score for its anticholinergic strength and add those scores up across all preparations — used above all in research and in pharmacy.

9. What you can do in practical terms

The route from suspicion to clarity is manageable — above all it needs completeness.

1. Write everything down, genuinely everything. Prescription medicines, over-the-counter products from the pharmacy and the chemist, sleeping aids, cold remedies, eye drops, sprays — and food supplements, see Supplements and medications.
2. Note the symptoms and when they started. How long have you had the dry mouth, how long the forgetfulness? What was newly started or increased during that period?
3. Ask about a medication review at the pharmacy. This goes through your entire medication systematically, looking for duplications, interactions and unfavourable combinations — and the anticholinergic burden is expressly part of it.^⁵
4. Take the result to the practice. The pharmacy suggests, the practice decides. Ask for an appointment expressly devoted to reviewing your medicines.
5. Make changes one at a time. If something is stopped or replaced, then one preparation after another where possible — otherwise nobody will know afterwards what made the difference.

If you regularly take five or more preparations, the guide Polypharmacy is worth reading as well — it deals with the system behind the tidying up.

10. Never stop anything on your own initiative

This article may tempt you to have a clear-out of the medicine cabinet. Please do not do that on your own.

The one exception in the direction of taking the initiative yourself: over-the-counter preparations that you started yourself — a sleeping aid from the chemist, for example. Even here a conversation at the pharmacy makes sense, because such preparations too can produce rebound effects after prolonged use.

11. There is almost always an alternative

The good news to finish with: in most cases nobody has to simply put up with the complaints. For almost every anticholinergically burdensome group there is a more favourable route available today.^⁶

Two things call for honesty. Alternatives are not automatically more effective — sometimes the anticholinergic preparation is the only one that has worked for that particular person. And a switch is a change in its own right, with its own settling-in period. The decision always rests with the practice treating you.

12. How brite helps you with the anticholinergic burden

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