High use of common drugs linked to dementia, Alzheimer's

A new study has found a significant link between high use of anticholinergic drugs - including popular non-prescription sleep aids and the antihistamine Benadryl (diphenhydramine) - and increased risk of developing dementia and Alzheimer's disease in older people.

Many medications - including some popular over the counter drugs - have strong anticholinergic effects.

Anticholinergics are a class of drug that blocks the action of the neurotransmitter acetylcholine in the brain and body.

This can lead to many side effects, including drowsiness, constipation, retaining urine and dry mouth and eyes.

The researchers at the University of Washington School of Pharmacy in Seattle, report their findings in JAMA Internal Medicine.

Older adults should be aware that many medications - including some available without a prescription, such as over-the-counter sleep aids - have strong anticholinergic effects.

People should not stop their therapy but talk to their health care provider

The researchers urges people not to stop their therapy based on the findings of this study - they should talk to their health care provider, and also tell them about all their over-the-counter drug use.

In fact, health care providers should regularly review their older patients' drug regimens - including over-the-counter medications - to look for chances to use fewer anticholinergic medications at lower doses.

If providers need to prescribe anticholinergics to their patients because they offer the best treatment, then they should use the lowest effective dose, monitor the therapy regularly to ensure it's working, and stop the therapy if it's ineffective.

Although the link between raised risk of dementia and anticholinergics has been found before, the new study uses more rigorous methods - including over 7 years of follow-up - to establish the strength of the link. By accessing pharmacy records, the researchers were also able to include non-prescription use of anticholinergics in their data.

It is also the first study to show a dose-response effect, note the authors. That is, the higher the cumulative amount of drug taken, the higher the risk of developing dementia.

And another first for the study, is that it also shows that dementia risk linked to anticholinergics may persist long after people stop taking the drugs.

Taking anticholinergics for more than 3 years linked to higher dementia risk

For their study, the research team tracked nearly 3,500 men and women aged 65 and over with no dementia symptoms at the start of the study. The participants were part of the Adult Changes in Thought (ACT) study in Group Health, an integrated health care delivery system in Seattle.

To assess how much exposure the participants had to anticholinergic drugs, the researchers used computer records from the pharmacies that dispensed them.

From the pharmacy data they added up all the standard daily doses and worked out the cumulative anticholinergic exposure for each participant over the past 10 years. This was updated as participants were followed up for an average of 7 years.

Over the period of the study, nearly 800 participants developed dementia.

The results showed that the most commonly used medications were tricyclic antidepressants (for example, doxepin or Sinequan), first-generation antihistamines (chlorpheniramine, Chlor-Trimeton), and antimuscarinics for bladder control (oxybutynin, Ditropan).

The researchers estimated that people taking at least 10 mg per day of doxepin, 4 mg per day of chlorpheniramine, or 5 mg per day of oxybutynin for more than 3 years would be at greater risk for developing dementia.

The researchers say there are alternative non-anticholinergic drugs for doxepin and chlorpheniramine. 

For example, to treat depression there are the selective serotonin re-uptake inhibitor (SSRI) like citalopram (Celexa) or fluoxetine (Prozac). And there are second generation antihistamines like loratadine (Claritin) for allergies.

However, while there are not many alternatives to oxybutynin for increasing bladder control, she suggests behavioral changes may be an option.

Some of the ACT participants have agreed to have their brains autopsied after they die. 

This might reveal if taking anticholinergic medications is more likely to result in brain changes that are characteristic of people who develop Alzheimer's disease.

Funds for the study came from the NIH's National Institute on Aging and the Branta Foundation.

References:

1. Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study, Shelly L. Gray et al., JAMA Intern Med, published online 26 January 2015, abstract.
2. University of Washington School of Pharmacy news release, accessed 27 January 2015.