Some OTC Drugs Linked to Dementia

By Jane Farrell

Researchers say that taking some commonly used drugs at a higher dose for a longer time carries a significantly increased risk for developing dementia, including Alzheimer’s.

The drugs include such familiar remedies as nonprescription diphenhydramine (Benadryl).

The study, published in JAMA Internal Medicine, is the first to show such a link. And it’s the first to suggest that the dementia risk may persist and may even be irreversible even years after people stop taking the drug.

“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,” said Shelly Gray, PharmD, MS, the first author of the report, which tracks nearly 3,500 Group Health seniors participating in the long-running Adult Changes in Thought (ACT), a joint Group Health–University of Washington (UW) study. “And they should tell their health care providers about all their over-the-counter use.” Anticholinergic drugs block the neurotransmitter acetylcholine; that can cause side effects including drowsiness and constipation.

Gray, who is a professor, the vice chair of curriculum and instruction, and director of the geriatric pharmacy program at the UW School of Pharmacy, also cautioned that “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.”

The most commonly used medicines in the study were tricyclic antidepressants like doxepin (Sinequan), first-generation antihistamines like chlorpheniramine (Chlor-Trimeton), and antimuscarinics for bladder control like oxybutynin (Ditropan).

People taking at least 10 mg/day of doxepin, 4 mg/day of chlorpheniramine, or 5 mg/day of oxybutynin for more than three years would be at greater risk for developing dementia, according to the study. Gray said substitutes are available for the first two: a selective serotonin re-uptake inhibitor (SSRI) like citalopram (Celexa) or fluoxitene (Prozac) for depression and a second-generation antihistamine like loratadine (Claritin) for allergies..

“If providers need to prescribe a medication with anticholinergic effects because it is the best therapy for their patient,” Dr. Gray said, “they should use the lowest effective dose, monitor the therapy regularly to ensure it’s working, and stop the therapy if it’s ineffective.”

Some participants in the ACT study have agreed to have their brains autopsied after they die. That will enable researchers to determine whether participants who took anticholinergic medications have more Alzheimer’s-related abnormalities in their brains than nonusers.