The Increasing Burden of Anticholinergic Medicines

Anticholinergics are drugs that block acetylcholine receptors in both the central and peripheral nervous systems, leading to an inhibition of the parasympathetic nervous system (also known as the rest and digest system).1 It is through this blockade that anticholinergics exert effects such as decreased respiratory secretions, gastrointestinal motility, and increased bronchodilation.1 These medications are used to treat many conditions including Parkinson’s disease, chronic obstructive pulmonary disease (COPD), urinary incontinence, allergies, asthma, the symptoms of coughs and colds, and motion sickness. However, due to their widespread activity across different body systems, anticholinergics are notorious for causing unintended adverse effects.1,2 Commonly used drugs with well-known anticholinergic effects include tricyclic antidepressants, sedating antihistamines, antipsychotics and bladder antispasmodics.1 However, there are other drug classes that possess low level anticholinergic activity such as SSRIs and opioids (See Table 1).2,4 The cumulative effect of taking multiple medicines with anticholinergic activity has been termed anticholinergic burden.5 As the burden increases, so too does the possibility of experiencing side-effects.6

Anticholinergic side effects can be more pronounced in people aged 65 years and older due to age related changes in pharmacodynamic and pharmacokinetic processes, existing frailty, and polypharmacy.6 Literature reports that 20-50% of older patients are prescribed drugs with anticholinergic properties.8 In this population, anticholinergic burden is associated with poor health outcomes including a 60% increase in fall-related hospitalisation, 50% increased risk of dementia and a 30% increase in mortality.8 The number of patients experiencing anticholinergic burden appears to be increasing over time, thus understanding, assessing, and reducing anticholinergic burden (where possible) is an important aspect for improving patient health outcomes.6-8

Currently, there is no standardised way to assess anticholinergic burden.6,7 To date there have been several tools developed such as the Anticholinergic Drug Scale (ADS), the Anticholinergic Cognitive Burden Scale (ACB) and the Anticholinergic Risk Scale (ARS). Some tools, such as the Drug Burden Index (DBI), which is used throughout Australia, measures both anticholinergic and sedative drug use.6 Typically, the tools classify all medications a patient takes based on their anticholinergic potential, usually on a scale of 0 (low potential) to 3 (high potential) points.6,7 The major drawback to the use of these tools is the variation between the scales, as they all use different criteria to assess anticholinergic potential and may weigh the same drug differently. For example, the ACB scores paroxetine with an anticholinergic burden of 3, while the ARS scores it as 1.4,9

Although, the score may differ depending on the tool used, they may be useful to identify anticholinergic medicines and their overall burden.2,4,9

Deprescribing is a patient-centred process which aims to cease potentially inappropriate medications that may be contributing to adverse effects, have minimal treatment benefit or are no longer required as the goals of care have changed. It can be an effective way of reducing polypharmacy and subsequently a patient’s anticholinergic burden.6,10 This optimisation of medication may result in decreased falls, reduced frailty and improved quality of life.6,10 The Primary Healthcare Network in Tasmania has a number of deprescribing guides, including an anticholinergic specific guideline which can assist clinicians with the process.11 Importantly, the key to effective deprescribing is ensuring that it is a shared-decision making process, actively involving the patient at all stages. If it is necessary for an anticholinergic medicine to continue, other strategies include reducing the dose to the minimum required, trialling alternate medications or non-pharmacological therapies, or pre-emptively managing potential side effects.6,12

A thorough medication review can be helpful in recognising over-the-counter anticholinergics such as antihistamines, travel sickness medications and antidiarrhoeals (See Table 2).

A medicine review completed by a pharmacist can assist in highlighting anticholinergic burden, adverse effects, and recommending potential medicines that could be deprescribed.

The main goal in assessing anticholinergic burden is to highlight the potential adverse effects this cumulative effect can have on an older patient’s cognitive and functional capacity.

Table 1: Common Prescription Medications with Anticholinergic Activity4,14

Alprazolam, Aripiprazole, Asenapine, Atenolol, Buproprion, Captopril, Codeine, Colchicine, Diazepam, Digoxin, Fentanyl, Furosemide, Fluvoxamine, Haloperidol, Hydrocortisone, Isosorbide, Metoprolol, Morphine, Prednisolone, Risperidone, Warfarin, Oxycodone, Tramadol

Amantadine, Carbamazepine

With vigilance and action of all healthcare providers and a patient-centred approach, there is a great potential for harm minimisation and improved patient outcomes.

Acclidinium, Amitriptyline, Atropine, Clozapine, Chlorpromazine, Doxepin, Glycopyrronium, Ipratropium Nortriptyline, Olanzapine, Oxybutynin, Paroxetine, Tiotropium, Umeclidinium, Tapentadol

Table 2: Over-The-Counter Medications with Anticholinergic Properties4,14

Drug Formulation Examples

Pseudoephedrine Oral decongestants

Brompheniramine, Chlorpheniramine, Dimenhydrinate, Diphenhydramine, Cold and allergy medicines

Doxylamine, Promethazine

Fexofenadine, Cetirizine, Loratadine, Desloratadine, Levocetirizine, Ipratropium

Atropine Hyoscine

Loperamide Metoclopramide

Sleep aid, sedating allergy medications

Non-sedating allergy medications

Anti-diarrhoeal medication

Travel sickness or stomach cramps

Anti-diarrhoeal medication

Migraine associated nausea medication

References are available on request.