Anticholinergic drugs in the elderly patients

Many drugs commonly used in the clinical practice have an anticholinergic activity. These are mostly psychotropic drugs like tricyclic antidepressants and antipsychotics, but also drugs that target other organs and apparatus, like for example first generation antihistaminics or furosemide (see table).
Anticholinergic drugs could cause gastrointestinal toxicity (for example dry mouth, nausea, constipation, abdominal cramps), urinary toxicity (acute urinary retention), ocular toxicity (cycloplegia, ocular hypertension up to acute glaucoma) and cardiac toxicity (arrhythmia). Particularly relevant is the neurological toxicity, that can manifest with mental confusion, vertigo, syncope, drowsiness, lethargy and, especially in the elderly patients, irritability, dyskinesia, insomnia.

A particular susceptibility

Elderly patients are particularly susceptible to the neurological toxicity of anticholinergic drugs because of:

• physiological and pathological modifications related to aging, such as an increased permeability of the hematoencephalic barrier and the reduction of the acetylcholine pools in the body
• use of many drugs with this effect. On this regard, it has been proved that anticholinergics are administered to 90% of over-75 people in the general population.^1,2 In long-term care patients in nursing homes, more than 30% takes two or more anticholinergic drugs and 5% takes even five of them.³

Cognitive consequences

Evidences are accumulating in literature, showing how anticholinergic drugs contribute to alter the cognitive functions in various areas, playing a relevant role in the development of acute confusional status, mild cognitive impairment (MCI), up to increase the risk of dementia.
A study carried out in 2014 over a cohort of 3435 patients with average age of 74 years and followed for 10 years has shown that a continuative exposure to anticholinergic drugs increased significantly the risk of Alzheimer dementia (HR 1.63, CI 95%: 1.24-2.14) and dementia for any cause (HR 1.54, CI 95%: 1.21-1.96).⁴ Similarly, from a prospective study that enrolled 36015 patients with average age of 83 years emerged that the use of anticholinergic drugs is associated to an increased risk of hospitalization for delirium. In particular, the risk of this event increased when the patients were administered two anticholinergic drugs (HR 2.58, CI 95%: 1.91-3.48) or three (HR 3.87, CI 95%: 1.83-8.21).⁵
In another study carried out on 372 over-60 patients, the use of anticholinergic drugs was associated to worse scores in a series of neuropsychological tests that measured reaction times, attention, verbal and non-verbal memory, language functions and visual-spatial skills.⁶
These negative cognitive effects also translate into worse physical performances for the elderly patients who take these drugs. It has been shown, in fact, that even when adverse reactions are not manifested, anticholinergic drugs can worsen mobility, muscular strength and balance and, in the end, this has an impact on the self-sufficiency of the elderly living in their own houses.¹

Non-neurological effects

Besides the neurological effects, cardiological effects of the therapy with anticholinergic drugs can cause important consequences on health. A recently published study focussed on the impact of anticholinergic drugs in the cardiopathic elderly patients and enrolled 3761 people (average age 83 years, average follow-up 1.4 years).³ In the analysis, corrected for the confounding factors, patients with low anticholinergic burden (HR 1.46, CI 95%: 1.12-1.90) and moderate-high (HR 1.41, CI 95%: 1.11-1.79) had an increased risk of major cardiovascular events. The incidence of these events was higher in the subjects with coronaropathy, suggesting that coronary diseases could provide a favorable substrate for the manifestation of the arrhythmogenic effects of anticholinergics.

Evaluation instruments

As already mentioned, there are many anticholinergic activity drugs (see table). On this regard, it should be highlighted that in the last years many instruments have been developed to measure the effect of cumulative exposure to these drugs: the Anticholinergic Cognitive Burden Scale (ACB), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Drug Scale (ADS).

Although heterogeneous, these instruments are useful to evaluate the total anticholinergic burden and can therefore become important instruments for the prescribers. In practice, it is essential that the doctor in charge of the elderly patient knows the potential anticholinergic activity of the drugs and carefully evaluate the appropriateness of prescribing a drug not only based on the guidelines, but also taking into care the anticholinergic burden, in order to avoid hospitalization and the development of disability, dementia and cardiovascular events.