Drug-class library
Anticholinergic burden is not a drug class. It is a property of a whole medication list, produced by drugs from many different classes that each look harmless on their own line.
Before you read on
Never stop or change a prescribed medication without speaking to your own prescriber. Several of the classes described on this site rebound, or cause a withdrawal syndrome, when they are stopped abruptly, and some have to be reduced gradually over weeks or months under supervision. Nothing here is advice about your own medication, and nothing here is a reason to change anything on your own.
What it is
Many medicines block acetylcholine as a side effect rather than as their purpose. Each may do so weakly. Added together across a list of eight or ten drugs, the combined effect produces dry mouth, blurred vision, constipation, urinary retention, confusion and falls — and the connection to any individual drug is invisible, because no individual drug is doing much.
Which classes carry it
The largest study to quantify this classified 56 strong-anticholinergic drugs into eleven classes by main indication. Ranked by how often they appeared in the prescribing records of 58,769 people with dementia:
| Class | Prescribed to (% of cases studied) |
|---|---|
| Anticholinergic antidepressants, including tricyclics | 27.1% |
| Antivertigo agents and antiemetics | 23.8% |
| Bladder antimuscarinics | 11.7% |
| First-generation antihistamines | 11.0% |
| Gastrointestinal antispasmodics | 6.9% |
| Antimuscarinic bronchodilators | 6.6% |
| Antipsychotics | 3.1% |
| Antiepileptics | 2.4% |
| Skeletal muscle relaxants | 0.7% |
| Antiparkinson agents | 0.5% |
| Antiarrhythmics | 0.1% |
The acute harms are the well-established ones
These are not in dispute and they are in the FDA-approved labeling. The label for a common bladder antimuscarinic states that “a variety of CNS anticholinergic effects have been reported, including hallucinations, agitation, confusion and somnolence,” advises monitoring “particularly in the first few months after beginning treatment or increasing the dose,” and adds a specific caution in “patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.” It is contraindicated in urinary retention, gastric retention and uncontrolled narrow-angle glaucoma.
For delirium the relationship is temporal and measured within individuals. A prospective cohort of 278 medical inpatients aged 65 and over with delirium found that an increase in delirium severity was significantly associated with anticholinergic exposure on the previous day, adjusting for dementia and baseline severity — and dementia did not modify the association.
A systematic review of 27 studies found all but two reported an association between anticholinergic activity of medications and either delirium, cognitive impairment or dementia.
Falls
A systematic prognostic review of eight studies covering 274,647 adults aged 65 and over found all eight showed some association between anticholinergic score and increased fall risk, most clearly at moderate to high burden. The honest caveat the authors state: all eight were rated high risk of bias in at least one domain and five in three or more, and the evidence for low burden is unclear. No study compared two scales directly, so none is established as the better falls predictor.
What the evidence does and does not show
Sedating medications impair gait, balance and reaction time, and their labels say so. That part is not in doubt. What has not been shown is that a deprescribing program reduces fall rates — the trials that tested it were small, short, and mostly measured a medication count rather than a fracture. Those are two different questions, and absence of evidence from underpowered trials is not evidence that the drugs do not cause falls. What the evidence actually shows about deprescribing and falls.
The dementia question — where the overstatement lives
Two large observational studies dominate this literature and they broadly agree with each other.
- A nested case-control study within a UK primary-care database, covering 58,769 people with a dementia diagnosis and 225,574 matched controls aged 55 and over, found adjusted odds ratios rising with cumulative exposure to 1.49 (95% CI 1.44 to 1.54) at the highest band — roughly three years of daily use of one strong anticholinergic at the minimum effective dose for older people. By class at that exposure: antipsychotics 1.70, bladder antimuscarinics 1.65, antiparkinson agents 1.52, antiepileptics 1.39, antidepressants 1.29. No significant increase for antihistamines, gastrointestinal antispasmodics, antimuscarinic bronchodilators, antiarrhythmics or skeletal muscle relaxants.
- A case-control study in a different UK database, covering 40,770 patients aged 65 to 99 with dementia and 283,933 controls, found an adjusted odds ratio of 1.11 (95% CI 1.08 to 1.14) for any drug scored as definitely anticholinergic, with risk rising for antidepressant, urological and antiparkinson drugs — and, again, no distinctive link for gastrointestinal drugs.
Neither study establishes causation, and both say so. The first states plainly that it “has shown associations, but is not able to evaluate causality,” that residual confounding and indication bias are possible, and that it is “impossible to entirely exclude protopathic effects arising from treatment for very early preclinical effects of dementia.”
Reverse causation, demonstrated inside the data
The clearest demonstration of the problem comes from inside the study most often used to make the claim. Its antipsychotic association — the largest in the whole analysis, at 1.70 — was not significant once prescriptions in the five years before diagnosis were excluded. The authors say this “suggest[s] that the association may be due to protopathic bias”: the antipsychotics were being prescribed for the early behavioral symptoms of dementia, not causing it.
Dementia has a long prodrome. Depression, urinary symptoms and behavioral change are themselves early features of it, and they are treated with exactly these drugs. That is why the phrase “anticholinergics cause dementia” goes beyond what this literature supports, and why the population-attributable fraction reported in that study — which its authors present explicitly as conditional on causality — should not be quoted as a fact.
The acute harms are reason enough to add up the burden. The dementia question does not need to be settled for the review to be worth doing, and overstating it costs credibility that the solid findings would otherwise have.
The scales, and why the number needs a name attached
Four are in common use. The Anticholinergic Cognitive Burden scale grades drugs 0 to 3 by anticholinergic activity and is the most frequently validated. The Anticholinergic Drug Scale was validated against serum anticholinergic activity — though it explained under 10% of the variance in that measure, which its own authors report. The Anticholinergic Risk Scale showed adjusted relative risks of 1.3 to 1.9 for anticholinergic adverse effects across two validation cohorts. The Drug Burden Index is different in kind: it is dose-based rather than an expert ranking, and covers sedative as well as anticholinergic exposure.
They disagree. A systematic review of seven expert-based scales found the ratings inconsistent, with quetiapine rated high anticholinergic activity in one, moderate in another, and low in two others. The authors conclude “there is not one standardised tool for measuring anticholinergic burden.” Any burden score recorded in a chart should name the scale that produced it, or it is not interpretable by whoever reads it next.
Why the Drug Burden Index is worth knowing about
In 3,075 well-functioning community-dwelling adults aged 70 to 79, a one-unit increase in the Drug Burden Index was associated with a 0.15-point deficit in physical function — more than three times the effect associated with a single comorbid illness — and a 1.5-point deficit on a cognitive processing test. That is the best available answer to the question of what medication burden actually costs a person.
Common questions
Do anticholinergic medicines cause dementia?
The association is real in two large observational studies. Causation is not established, and both sets of authors say so. The clearest evidence against a simple causal reading comes from within the larger study itself: its strongest single association disappeared once prescriptions in the five years before diagnosis were excluded, which is what reverse causation looks like. The acute harms — confusion, delirium, constipation, urinary retention, falls — are not in dispute. Assessment of individual care needs.
What should be done with an anticholinergic burden score?
Treat it as a prompt to look at the list with a prescriber, not as a threshold that triggers stopping something. The scales disagree with each other, they measure exposure rather than an individual’s response, and some of the drugs carrying the burden are treating something that matters. The medication review.
Back to the drug-class library.
Antidepressants are a major source of this burden
An older adult prescribed amitriptyline for sleep or for neuropathic pain is carrying anticholinergic burden whether or not anyone has used that word. The tricyclics — amitriptyline, nortriptyline, doxepin, imipramine — are among the most anticholinergic drugs in common use, and among the SSRIs, paroxetine carries meaningful anticholinergic activity where most others do not.
This matters for two reasons. First, it is the largest single category in the exposure data: anticholinergic antidepressants including tricyclics were prescribed to 27.1% of the cases in the largest study to quantify this — more than any other class. Second, the indication is often not depression. Low-dose amitriptyline prescribed for sleep or pain delivers the same muscarinic blockade as a full antidepressant dose delivers, in a person who may also be on a bladder antimuscarinic and an antihistamine.
The mechanism is muscarinic blockade, not GABA-A modulation, and the effect estimates on this page — modest, hedged, and observational — are the right ones for it. Do not read the benzodiazepine memory material across to this class; they are different drugs doing different things. Benzodiazepines.
It is also not a statement that all antidepressants carry equal cognitive load. They do not, and which one a person is on matters a great deal.
References
- 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 Internal Medicine. 2019;179(8):1084–1093. PMID 31233095 · DOI 10.1001/jamainternmed.2019.0677.
- Richardson K, Fox C, Maidment I, et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018;361:k1315. PMID 29695481 · DOI 10.1136/bmj.k1315.
- Han L, McCusker J, Cole M, Abrahamowicz M, Primeau F, Elie M. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Archives of Internal Medicine. 2001;161(8):1099–1105. PMID 11322844 · DOI 10.1001/archinte.161.8.1099.
- Campbell N, Boustani M, Limbil T, et al. The cognitive impact of anticholinergics: a clinical review. Clinical Interventions in Aging. 2009;4:225–233. PMID 19554093 · DOI 10.2147/cia.s5358.
- Stewart C, Taylor-Rowan M, Soiza RL, Quinn TJ, Loke YK, Myint PK. Anticholinergic burden measures and older people’s falls risk: a systematic prognostic review. Therapeutic Advances in Drug Safety. 2021;12:20420986211016645. PMID 34104401 · DOI 10.1177/20420986211016645.
- Salahudeen MS, Duffull SB, Nishtala PS. Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review. BMC Geriatrics. 2015;15:31. PMID 25879993 · DOI 10.1186/s12877-015-0029-9.
- Boustani M, Campbell N, Munger S, Maidment I, Fox C. Impact of Anticholinergics on the Aging Brain: A Review and Practical Application. Aging Health. 2008;4(3):311–320. DOI 10.2217/1745509X.4.3.311. Not indexed in PubMed; verified through Crossref. Cite by DOI.
- Carnahan RM, Lund BC, Perry PJ, Pollock BG, Culp KR. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. Journal of Clinical Pharmacology. 2006;46(12):1481–1486. PMID 17101747 · DOI 10.1177/0091270006292126.
- Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Archives of Internal Medicine. 2008;168(5):508–513. PMID 18332297 · DOI 10.1001/archinternmed.2007.106.
- Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to define the functional burden of medications in older people. Archives of Internal Medicine. 2007;167(8):781–787. PMID 17452540 · DOI 10.1001/archinte.167.8.781.
- Fox C, Richardson K, Maidment ID, et al. Anticholinergic medication use and cognitive impairment in the older population: the Medical Research Council Cognitive Function and Ageing Study. Journal of the American Geriatrics Society. 2011;59(8):1477–1483. PMID 21707557 · DOI 10.1111/j.1532-5415.2011.03491.x.
- By the 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 2023;71(7):2052–2081. PMID 37139824 · DOI 10.1111/jgs.18372.
- Lee J, Negm A, Peters R, Wong EKC, Holbrook A. Deprescribing fall-risk increasing drugs (FRIDs) for the prevention of falls and fall-related complications: a systematic review and meta-analysis. BMJ Open. 2021;11(2):e035978. PMID 33568364 · DOI 10.1136/bmjopen-2019-035978.
- 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 Internal Medicine. 2019;179(8):1084–1093. PMID 31233095 · DOI 10.1001/jamainternmed.2019.0677.
- By the 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 2023;71(7):2052–2081. PMID 37139824 · DOI 10.1111/jgs.18372.
Bibliographic records on this page were retrieved from PubMed. Every reference links to its DOI or PubMed record.
Written and medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP, founder and medical director of DWARAA. Last reviewed . This page is educational. DWARAA does not prescribe, deprescribe, diagnose or treat.