People aged over 65 who take some common over-the-counter (OTC) or prescribed medicines for allergy, depression or an overactive bladder have an increased risk of developing dementia if they take them at high dose for a long time, according to research published in JAMA Internal Medicine
on 26 January 2015.
The data confirm a dose–response relationship to developing dementia and show that the risk remains even if the patient stops taking the medicines.
Shelly Gray, the lead researcher and director of the geriatric pharmacy programme at the University of Washington in Seattle, says that older patients should be made aware that many drugs — some of which are available OTC — have “strong anticholinergic effects” and that they should ask their pharmacist or prescriber for alternatives.
“For allergies, there are OTC alternatives that don’t have anticholinergic effects that would be a better option for older adults,” she says. “For insomnia, non-drug therapy, such as avoiding naps and restricting caffeinated drinks late in the day, is the first-line management strategy.”
The research involved 3,434 patients who were enrolled with Group Health — a US healthcare delivery system — for at least 10 years before the start of the study. The average age was 74.4 years and 91.4% of the patients were white. Patients were recruited between 1994 and 1996, and again from 2000 to 2003.
The researchers set out to look at the risk of developing dementia in patients who took medicines with an anticholinergic effect. Some 78.3% of the cohort had at least one prescription for an anticholinergic drug in the previous 10 years.
The researchers analysed pharmacy dispensing data for each patient, including for anticholinergic medicines such as tricyclic antidepressants, antihistamines and bladder anti-muscarinics; the most common of these were doxepin, chlorphenamine and oxybutynin. The researchers recorded the name of the product, the strength, the route of administration, the date dispensed and the amount.
The patients were tested for signs of dementia at the outset and every two years. The researchers found that 23.2% of patients developed dementia during a mean follow-up of 7.3 years. Of that group, 79.9% had possible or probable Alzheimer’s disease.
There was a 10-year accumulated dose–response relationship for both dementia and Alzheimer’s disease. Patients taking the highest daily dose had a significantly increased risk for dementia or Alzheimer’s disease (hazard ratios 1.54, 95% confidence interval 1.21–1.96, and 1.63, 95% CI 1.24–2.14, respectively).
The researchers note that patients would reach the heaviest level of exposure by taking 10mg per day of doxepin, 4mg per day of chlorphenamine, or 5mg per day of oxybutynin for more than three years.
“Older patients should tell their healthcare providers about all their over-the-counter use,” says Gray. “If providers need to prescribe a medication with anticholinergic effects because it is the best therapy for their patient, they should use the lowest effective dose, monitor the therapy regularly to ensure it’s working, and stop the therapy if its ineffective.”
 Gray SL, Anderson ML, Dublin S et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Internal Medicine 2015, doi: 10.1001/jamainternmed.2014.7663.