[113] How well do you know your anticholinergic (antimuscarinic) drugs?

[113] How well do you know your anticholinergic (antimuscarinic) drugs?

Anticholinergic drugs, prescribed for a variety of clinical conditions, are amongst the most frequently used prescription drugs in BC (Table 1). Also referred to as “antimuscarinics,” such drugs specifically block muscarinic receptors for acetylcholine (ACh).1 Muscarinic ACh receptors are important in the parasympathetic nervous system that governs heart rate, exocrine glands, smooth muscles, as well as brain function. In contrast, nicotinic ACh receptors stimulate contraction of striated muscles. This Letter is intended to remind clinicians of commonly used drugs that have anticholinergic (AC), or technically, antimuscarinic properties, and of their potential adverse effects.

Table 1: Anticholinergics in the Top 100 (BC Data, 2016)

Antidepressants: amitriptyline*, bupropion, citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine
Antipsychotics: aripiprazole, clozapine, olanzapine, quetiapine, risperidone
Drugs for insomnia: trazodone, zopiclone
Drugs for pain: amitriptyline*, cyclobenzaprine

* nortriptyline and other TCAs are similar to amitriptyline

Beneficial and harmful effects of anticholinergic drugs have been known for centuries. In Homer’s Odyssey, the nymph pharmacologist Circe utilized central effects of atropinics in the common plant jimson weed (Datura stramonium) to cause delusions in the crew of Odysseus. Believing they had been turned into pigs, they could be herded.2

Sometimes a drug is recommended specifically for its anticholinergic potency. Patients using drugs such as benztropine to counteract the “extrapyramidal” effects of dopamine blockade, or drugs such as oxybutynin to reduce bladder contractility, are relying on deliberate antagonism of muscarinic neurotransmission by ACh.

Many drugs have potential for AC toxicity

Anticholinergic effects are also an unwanted consequence of therapy (Table 2). The number of such drugs is larger than most clinicians realize.3 Lists vary,4 and may not include drugs whose active metabolites are potently antimuscarinic,5 or which often cause typical AC adverse effects such as dry mouth or urinary retention.6 People taking antihistamines, antidepressants, antipsychotics, opioids, antimuscarinic inhalers, or many other drugs need to know that blockade of ACh receptors can cause bothersome or even dangerous adverse effects (Table 3).

Table 2: Common drug classes with AC properties

Antidepressants: multiple
Antihistamines: found in many over the counter cold remedies and sleep aids, and in dimenhydrinate/Gravol
Antimuscarinic inhalers: all
Antipsychotics: old and new
Antispasmodics: e.g. hyoscine/Buscopan
Bladder drugs: e.g. oxybutynin, tolterodine
Opioids: all

Table 3: Anticholinergic adverse effects

Body system Potential adverse effects
Brain Visual/auditory/sensory hallucinations

Tremulousness/myoclonic jerking

Memory impairment, cognitive impairment e.g.“brain fog”, altered mental status (delirium)

Heart Tachycardia
Eyes Dry eyes

Difficulty adjusting visual focus (lens accommodation)

Sensitivity to bright light (dilated pupils)

GI tract Impaired stomach emptying/increased esophageal reflux;


Mouth Dry mouth/impaired speech articulation

Severe tooth decay

Difficulty swallowing due to lack of saliva

Skin Decreased sweating/dry skin
Bladder Difficulty starting urination/impaired bladder emptying

Urinary retention/overflow incontinence

Subtle and not-so-subtle toxicity

Students often learn the adverse effects of anticholinergics from a mnemonic, e.g.: “Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone.” This refers to pupillary dilation and impaired lens accommodation, delusions, hallucinations or delirium, flushing, hyperthermia, dry mucosae and skin, gastrointestinal and bladder paralysis, and tachycardia.7 Shorter mnemonics fail to capture the broad range of anticholinergic toxicity shown in Table 3.

Drug product monographs and Wikipedia are easily accessible online resources to identify AC toxicity by simple word searches. For example, searching for the word “anticholinergic” in the 2017 revised product monograph for Seroquel XR (quetiapine) yields a discussion of urinary retention observed in patients during post-marketing surveillance.5 The monograph also explains that this is probably due to the active metabolite, present in anyone who takes quetiapine. Monographs for all antimuscarinic inhalers specifically warn of potential AC effects.

Long term use linked to dementia

A recent narrative review examined the connection between long-term use of AC drugs and the risk of dementia and identified 4 observational studies of elderly people in France, Germany, and the U.S.8

Based on signals from 3 of these 4 studies, the review authors conclude that AC drugs may increase the risk of dementia. They also note signals that people who stop using anticholinergics are at lower risk of dementia than those who continue, and that patients who take higher doses of more potent AC drugs are at greater risk of dementia.

The 4 observational studies were not randomized controlled trials and thus cannot prove that anticholinergic drugs cause dementia. All study authors attempted to correct for potential confounding, but only one study used propensity score matching to minimize confounding. This did not identify a relationship between use of paroxetine and dementia in nursing home residents.8,9

We conclude that there is some reason to be concerned that long-term anticholinergic drug use might increase the subsequent risk of dementia, even though this conclusion needs to be confirmed by longer and more methodologically rigorous studies. Other long-term effects such as increased dental caries are unquestioned.3

Prescribing Principles

  • Before prescribing, consider a patient’s total anticholinergic burden by reviewing all drugs. Inform patients about anticholinergic effects of over the counter drugs (e.g. “Gravol” or “sleep aids” containing diphenhydramine).
  • Alert patients and families that using drugs that block cholinergic neurotransmission in the brain can increase the risk of cognitive impairment and may be risky long-term.
  • Prescribe anticholinergics only for a clear indication. Document the purpose in the clinical record and on prescription directions (“indication-based prescribing”). This should appear on the medication container label and will facilitate periodic review and deprescribing.
  • Use low doses for the shortest possible time; reassess often for predictable adverse effects (Table 3). Ask about subtle manifestations of anticholinergic toxicity such as impaired cognition, impaired visual accommodation, slurred speech from a dry tongue and mouth, reflux from delayed stomach emptying, or frequent urination due to incomplete voiding. If you suspect dry mouth, see whether a swish of water improves speech.
  • If unsure whether antimuscarinic effects may be in play, consult online resources, including drug monographs.

The draft of this Therapeutics Letter was submitted for review to 130 experts and primary care physicians in order to correct any inaccuracies and to ensure that the information is concise and relevant to clinicians.

The Therapeutics Initiative is funded by the BC Ministry of Health through a grant to the University of BC. The Therapeutics Initiative provides evidence-based advice about drug therapy, and is not responsible for formulating or adjudicating provincial drug policies.
ISSN 2369-8691 (Online) <||> ISSN 2369-8683 (Print)


  1. https://en.wikipedia.org/wiki/Anticholinergic; Montastruc JL, Durrieu G, Sommet A, et al. Anticholinergics, antimuscarinics or atropinics?  About the words in pharmacology. Br J Clin Pharmacol 2010; 69(5): 561-2. DOI: 10.1111/j.1365-2125.2010.03633.x
  2. https://en.wikipedia.org/wiki/Circe
  3. Nguyen CT, MacEntee ML, Mintzes B, Perry TL. Information for physicians and pharmacists about drugs that might cause dry mouth: A study of monographs and published literature. Drugs and Aging 2014; 31(1):55-65. DOI: 10.1007/s40266-013-0141-5
  4. Hsu WH, Wen YW, Chen LK, Hsiao FY. Comparative Associations Between Measures of Anti-cholinergic Burden and Adverse Clinical Outcomes. Ann Fam Med 2017;15(6):561-9. DOI: 10.1370/afm.2131
  5. e.g. norquetiapine (desalkylquetiapine); see Seroquel XR (quetiapine) revised Canadian product monograph 2017, p. 44-73. https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/seroquel-xr-product-monograph-en.pdf
    (accessed August 28, 2018)
  6. e.g. duloxetine (Cymbalta) – see Cymbalta revised product monograph 2016. https://pdf.hres.ca/dpd_pm/00035593.pdf (accessed August 28, 2018)
  7. https://en.wikipedia.org/wiki/Toxidrome
  8. Gray SL, Hanlon JT. Anticholinergic medication use and dementia: latest evidence and clinical implications. Therapeutic Advances in Drug Safety 2016; 7(5):217–24. DOI: 10.1177/2042098616658399
  9. Bali V, Chatterjee S, Carnahan RM, et al. Risk of Dementia Among Elderly Nursing Home Patients Using Paroxetine and Other Selective Serotonin Reuptake Inhibitors. Psychiatr Serv 2015; 66(12):1333–40. DOI: 10.1176/appi.ps.201500011
  • Carl Whiteside
    Posted at 08:47h, 11 September Reply

    – An Excellent summary
    – Although long, it may be helpful to id more commonly used, cross the counter, AC drugs.
    – I like the inclusion of the mechanism of action of drugs you are highlighting in the Letters
    – Can we assume residents are automatically cc on these letters? If not I may be able to help with the FP residents.

  • Melodie Herbert
    Posted at 13:26h, 11 September Reply

    Thank you for another very informative drug review. It is dismaying to see that the SSRI’s, as well as older antidepressants have sufficient anticholinergic effects to be included in the list of drugs of concern. The recommendation overall is to use all of these drugs (with anticholinergic side effects) for indication, in the lowest effective dose, for the shortest possible time. However, it is also desirable for people with a recurrent mood disorder, to probably continue to take their SSRI forever, if it is helpful and tolerated, because discontinuation is associated with a very high rate of relapse.

    I wonder if you could quantify the degree of anticholinergic side effects a bit more? I suspect that Amitriptyline is much more anti-muscarinic, than is Citalopram, for example, based on the side-effect profile that most family doctors are familiar with.
    With respect to the risk of dementia, I wonder what effect anticholinergic drugs might (or might not) have on the development of neurofibrillary tangles and plaques, and death/drop out of cognitive neurons, with grey matter atrophy, as are seen in Alzheimer’s dementia? I would like to understand the process by which anticholinergic drugs might increase the actual risk of dementia, rather than this association noted in these studies.

  • Susan Inman
    Posted at 09:55h, 25 November Reply

    Susan: You wrote:

    If the purpose of this article is to improve ‘how well’ people know their anticholinergic drugs, shouldn’t it also include the abundant research on the value of anti-psychotic medications in helping people with schizophrenia recover from and maintain recovery from the psychotic part of their disorder? The spread of unbalanced messages like this does this population real harm.
    Seeing this level of bias makes me doubt any recommendations coming from this group.

    This Letter is intended to remind clinicians of commonly used drugs that have anticholinergic (AC), or technically, antimuscarinic properties, and of their potential adverse effects.

  • John Harrington
    Posted at 03:33h, 18 August Reply

    I understood that bupropion does not have anticholinergic properties. Could you cite your source for stating that it is?

    • Aaron M Tejani
      Posted at 14:25h, 18 November Reply

      Thank you for the question. We refer you to the product monograph that:
      1. Documents an adverse event profile that is similar to medications that are antimuscarinic
      2. States that bupropion has weak affinity (as opposed to no affinity) for muscarinic cholinergic receptors

      Source: https://pdf.hres.ca/dpd_pm/00040677.PDF

      These are the reasons we listed bupropion in Letter 113.

  • Alice
    Posted at 10:23h, 13 September Reply

    Prozac 50 mg daily…
    can this cause tachycardia!
    Will it lead to dementia?

    • Alan Cassels @ TI
      Posted at 16:08h, 16 September Reply

      Alice, as we mentioned in the letter, SSRI antidepressants are among those anticholinergic drugs associated with tachychardia and cognitive impairment so you should check with your own physician to consider your concerns about these side effects.

    Posted at 16:56h, 09 October Reply

    is lyrica safe to take

    • Alan Cassels @ TI
      Posted at 10:44h, 24 October Reply

      That drug goes by the generic name pregabalin and we have done a recent Therapeutics Letter on it, found here:
      We write that pregabalin “increases somnolence, dizziness, ataxia, weight-gain, peripheral edema, blurred vision, diplopia, and headache.”
      These are issues you’d probably want to discuss with your physician.
      cheers, Alan Cassels

      • Kathy keeler
        Posted at 21:20h, 18 November Reply

        What about GABA? Ty

  • Lana Langevin
    Posted at 11:57h, 07 April Reply

    I was under the assumption that Trazodone was not anticholinergic (ie. has no affinity for the muscarinic acetylcholine receptors).
    Can you explain why it is on the list?

    • Therapeutics Initiative
      Posted at 11:26h, 12 April Reply

      We have looked again and not found confirmation that trazodone blocks muscarinic cholinergic receptors (in vitro). However, the product monograph clearly indicates that trazodone does cause dry mouth and blurred vision, along with its many other adverse effects. One possible explanation for reduced salivation is blockade of salivary gland alpha-1 receptors (Settimo L, Taylor D. Evaluating the dose-dependent mechanism of action of trazodone by estimation of occupancies for different brain neurotransmitter targets. J. Paychopharmacology 2018, available open access here: https://journals.sagepub.com/doi/full/10.1177/0269881117742101). Another possible action could be via a metabolite (analogous to the potent anti-muscarinic effect of norquetiapine, an active metabolite of quetiapine), although we have not identified any report showing this.

  • Kathi Thibodeau
    Posted at 06:45h, 13 August Reply

    I would like to hear more about the findings of long term use of zoplicone.

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