Many older people take these medications, which include nonprescription diphenhydramine (Benadryl). JAMA Internal Medicinepublished the report, called “Cumulative Use of Strong Anticholinergic Medications and Incident Dementia.”
The study used more rigorous methods, longer follow-up (more than seven years), and better assessment of medication use via pharmacy records (including substantial nonprescription use) to confirm this previously reported link. It is the first study to show a dose response: linking more risk for developing dementia to higher use of anticholinergic medications. And it is also the first to suggest that dementia risk linked to anticholinergic medications may persist — and may not be reversible even years after people stop taking these drugs.
Older adults need to be aware that many medications — including some available without a prescription, such as over-the-counter sleep aids — have strong anticholinergic effects.
For instance, the most commonly used medications in the study were tricyclic antidepressants like doxepin (Sinequan), first-generation antihistamines like chlorpheniramine (Chlor-Trimeton), and antimuscarinics for bladder control like oxybutynin (Ditropan). The study estimated that 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. Dr. 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. It’s harder to find alternative medications for urinary incontinence, but some behavioral changes can reduce this problem.
Anticholinergic effects happen because some medications block the neurotransmitter called acetylcholine in the brain and body. That can cause many side effects, including drowsiness, constipation, retaining urine, and dry mouth and eyes.
“With detailed information on thousands of patients for many years, the ACT study is a living laboratory for exploring risk factors for conditions like dementia,” said Dr. Gray’s coauthor Eric B. Larson, MD, MPH. “This latest study is a prime example of that work and has important implications for people taking medications — and for those prescribing medications for older patients.”