The prevalence of potent anticholinergic use in the older population in England nearly doubled between 1990/93 and 2008/11. After adjustment for demographic variables, we found that participants in the later study (CFAS II) were 1.9 times more likely to be on potent anticholinergics as compared to participants in the earlier study (CFAS I). This was mainly due to increases in the availability and use of anticholinergic urologicals (common drugs were oxybutynin, solifenacin and tolterodine) and antidepressants (the most common being amitriptyline). More than one in five of those with an impairment in activities of daily living, and one in six of those with MMSE less than 21, indicating clinically significant cognitive impairment including dementia, reported use of a potent anticholinergic medication in CFAS II, both significantly higher than in CFAS I [21]. This is despite guidance suggesting cautious use of these drugs. Those with IADL disability had the greatest disproportionate increases in potent anticholinergic use. Women and older participants also had disproportionately greater increases in total anticholinergic burden between study periods.
A number of studies have described changes in the rates of anticholinergic prescribing [16, 17]. A study in Scotland examined changes in the numbers of prescriptions of anticholinergic medications, from 1995 to 2010, and found a statistically significant but modest increase in the number of older people prescribed any anticholinergic (20.7% vs 23.7%, p < 0.001) [16]. A repeated cross-sectional analysis of office-based outpatient visits for older people in the USA found that the prevalence of high-risk anticholinergic prescriptions was stable from 2006 to 2015; it increased from 6.1% in 2006–07 to 6.8% in 2008–09 and decreased to 4.7% by 2014–15 [17]. However, previous studies have not been able to include over-the-counter medication use nor describe use in vulnerable patient groups; the US study also only included prescriptions issued by the physician at the sampled visit.
We observed an increase in anticholinergic urological use between 1991 and 2011, partly because many of the commonly used urologicals were only introduced in the 1990s, or later. Other studies have also reported increases in the prescribing of anticholinergic urologicals [16, 22, 23]. A 23% increased number of new users of anticholinergics for overactive bladder was reported in a UK study (from 12,598 in 2004 to 15,441 in 2012) [23]. A significant increase in the proportion of women presenting to physicians with urinary incontinence then prescribed bladder anticholinergics was also reported in the US (16.7% in 1999 to 35.0% in 2009, p = 0.006) [22].
Use of anticholinergic antidepressants also increased between CFAS I and II; confirming other studies [24]. In addition to anticholinergic effects, antidepressants are associated with hyponatraemia [25, 26]. Even mild hyponatraemia induced by antidepressants may worsen cognition and cause falls compounding apparent anticholinergic effects [25]. Depression is also an early sign of dementia and therefore older people with depression may be particularly vulnerable to cognitive anticholinergic effects [27].
Anticholinergics can have a significant impact on morbidity in older people particularly those living with any form of clinically significant cognitive impairment including dementia [7, 12]. Anticholinergics can worsen dementia, cause numerous anticholinergic effects, both centrally and peripherally, and may be associated with an excess mortality [7, 12]. Equally importantly, anticholinergics could also worsen the quality of life of the older person and any informal (family) carer [28].
The large increase in the use of potent anticholinergics among people with clinically significant cognitive impairment and physical disabilities is particularly concerning. There is increasing evidence, from recent research, that such usage is associated with an increased risk of dementia [10, 11, 12]. Furthermore, anticholinergic cognitive effects are likely to have more severe consequences, such as medication errors, in people with less cognitive reserve for example dementia or traumatic brain injury [29]. Medication management itself is an instrumental activity of daily living with high demands on memory and executive function [30], and so anticholinergic induced cognitive impairment may increase the risk of both non-adherence to medication, and medication errors [30, 29]. This in turn will increase dependency on informal carers worsening the burden on informal carers [31].
Strengths and weaknesses
Frail older people with multi-morbidities including those with dementia are frequently excluded from controlled trials, and so effectiveness of anticholinergics is rarely directly assessed, and observational studies are vital for monitoring risks. Strengths of this study include the population-based sampling in CFAS from the same geographic areas 20-years apart and to ascertain key patient characteristics, cognition and disability associated with medication use. Although most anticholinergics are prescribed, a further strength of our study was the ability to more accurately capture the full range of anticholinergic use, by including OTC medications.
This appropriateness of prescribing was not assessed as part of the CFAS study. The increase in use of anticholinergics might reflect improvements in diagnosis and better access to treatment for conditions such as incontinence, depression and pain. Such conditions can be very debilitating, and for clinicians and patients the key issue is balancing the risks versus the benefits.
Our study has some limitations. The accuracy of the self-reported medication use and the duration of treatment is unknown. Although, to increase the accuracy of the reporting, interviewers requested, where possible, to see the medication packages (and repeat prescription scripts) to enter correct drug names, we cannot be sure if the participants were adherent to the medication. The data used is from 1990 to 1993 and 2008 to 2011 and therefore we recommend that the study is repeated with more recent data to examine whether the trends continue. Studies examining UK trends in anticholinergic medication use post 2011 are rare. Increased prescribing of anticholinergics for overactive bladder has been reported until 2012 for adults [23]. Warnings against antipsychotic use in dementia has decreased prescribing to these patients [32], but we lack information on the general older population. Antidepressant prescribing has been increasing from 2013 to 18, but detail has not been provided by anticholinergic antidepressants or for older people specifically [33].
We used the ACB scale to identify anticholinergic medications, however this is one of 18 different scales that all vary in their content and how they are derived and how anticholinergic activity is quantified [34]. However, the scales closely agree on which medications they classify as potently anticholinergic. The response rate was lower in CFAS II, and it is not clear whether this would under-estimate or over-estimate medication use in this cohort. We used inverse probability weights to correct age and sex distributions for non-response, and conducted analyses stratified by levels of cognitive function and disability, and so our findings are unlikely to be biased by differential non-response between cohorts [18]. Our study is descriptive and we did not have sufficient comorbidity data to sufficiently examine why older people in the various subgroups had increased anticholinergic use, but increased diagnoses of conditions for which anticholinergics are indicated for is likely a factor.
Future research
Further research is needed to monitor anticholinergic use within vulnerable populations, particularly older people living with clinically significant cognitive impairment including dementia, in the UK since 2011 and in other countries. We also need a clearer understanding of the relative risk versus benefit of anticholinergics and in whom the risk is greatest, and the effectiveness of interventions to reduce the harm associated with anticholinergics. Interventions to limit the use of inappropriate anticholinergics require development and testing; a realist approach, which focuses on the key importance of context and mechanism offers a promising avenue for such intervention development [35,36,37].
