Not Just a Product of Age: Anticholinergic Medications and Falls in Middle-aged Women

Elise Durgin, Pharm.D, Goodrich Pharmacy

Background: The risks of anticholinergic medication use in the elderly are well-documented. As anticholinergic burden increases, elderly patients find themselves at an increased risk of confusion, blurred vision, urinary retention, and constipation. A higher anticholinergic burden may also lead to falls, with the potential for catastrophic outcomes, including increased mortality. It is less understood whether the use of anticholinergic medications increases the risk of falls or fractures in younger populations.

Objective: The authors of A high anticholinergic burden is associated with a history of falls in the previous year in middle-aged women: findings from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) wished to examine the association between anticholinergic medication burden (ACB) and a history of falls, bone mineral density, and low trauma fractures in middle-aged women less than 65 years of age in a cross-sectional study utilizing data from APOSS.

Study design: Between the years 1990 and 1993, 7200 women aged 45-54 years were identified from a primary care patient registry for a study in Aberdeen, Scotland. Of these, 5119 elected to participate. Study participants completed both a dual energy X-ray absorptiometry(DXA) scan of the hip and lumbar spine and an osteoporosis risk factor questionnaire. Participants were also asked about comorbidities, including personal history of osteoporosis, rheumatoid arthritis, osteoarthritis, asthma, kidney disease, thyroid disease, diabetes, hypertension, myocardial infarction, and stroke. Information on the use of corticosteroids, calcium supplements, medications for osteoporosis, antiepileptic medications, diuretics, sex hormones and tamoxifen was also gathered. Between 1997 and 2000, these same individuals were invited for a follow-up visit. Participants’ weight, height, and physical activity level were collected, in addition to self-reported falls and fractures within the last 12 months. The ACB of the women who attended the follow-up visit was calculated using the Aging Brain Program’s ACB scoring table. Medications with more anticholinergic properties are assigned higher scores, up to a maximum score of three per medication. Medications such as amitriptyline, diphenhydramine, and scopolamine are examples of medications with the maximum ACB score of three. The sum of the ACB scores of the individual medications was used to determine the patient’s overall ACB score.

 Results: The average age of participants at follow-up was 54 years. As ACB score increased, the likelihood the person had fallen within the last year also increased. In fully adjusted logistic regression models, an ACB score greater than or equal to two was associated with a history of falls (1.80 [95% CI 1.25-2.60], P=0.002). Of the 3883 women that completed follow-up, 3293 (84.8%) had an ACB score of zero, 328 (8.4%) had ACB score of one, whereas 262 (6.7%) had an ACB score of two or more. The authors used an ACB score of two or greater in their analysis based on wider literature that associates a score of two or greater with worse outcomes, including increased mortality. As ACB score increased, participants’ age and BMI also increased, while physical activity decreased. It was also noted that patients with an ACB score of two or greater had the highest number of self-reported comorbidities. Additionally, the highest rates of corticosteroid, diuretic, and antiepileptic use was found in patients with ACB scores of two or more. There was no association between ACB and having ever fractured a bone, nor was there an association between ACB and having fractured a bone since the age of 50.

Conclusion: While this cross-sectional study is unable to determine causality, it sheds new light on the risks of anticholinergic medications in younger populations, specifically middle-aged individuals. Nearly one-third of patients with a high ACB score of two or more had fallen in the last year. Some may question whether the patients with high ACB scores in this study were less healthy, as evidenced by the higher rate of comorbidities and medication use. Poor health may have contributed to falling. Additionally, nearly 25% of patients did not complete the follow-up, which leads to questions about the applicability of these results. However, this data may change how we judge the appropriateness of anticholinergic medications in patients under 65 years of age. A history of falling is predictive of future falls, and is the strongest risk factor for low-trauma fractures in elderly patients.

Key Point: The use of multiple anticholinergic medications in younger patient groups, in this case more than 10 years before we consider the Beers criteria, is likely inappropriate. Pharmacists should educate patients about the risks of anticholinergic medications, regardless of age.

Reference:

1. Ablett AD, Wood AD, Barr R, et al. A high anticholinergic burden is associated with a history of falls in the previous year in middle-aged women: findings from the Aberdeen Prospective Osteoporosis Screening Study. Ann Epidemiol. 2018;28(8):557-562. doi:
10.1016/j.annepidem.2018.05.011.