February 13, 2015
Some drugs commonly used to treat hay fever, insomnia and depression have been linked to a higher risk of Alzheimer’s disease and other forms of dementia, a new study reports. And the longer the medications are taken, the greater the risk.
The drugs include many popular prescription and over-the-counter medications. They include tricyclic antidepressants like doxepin (Sinequan), antihistamines like chlorpheniramine (Chlor-Trimeton) and diphenhydramine (Benadryl), and bladder control drugs like oxybutynin (Ditropan).
All of the medications are known to block a brain chemical called acetylcholine, which transmits nerve signals throughout the brain and nervous system. The drugs are known as “anticholinergic agents” and are commonly taken for disorders ranging from allergies and bladder problems to sleep and mood disorders. Common side effects of anticholinergic drugs include drowsiness, sore throat, retaining urine, and dry mouth and eyes.
“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 study author Shelly Gray, director of the geriatric pharmacy program at the University of Washington School of Pharmacy. While anyone taking these drugs should not stop taking them without consulting their doctor, effective substitutes may be available.
A link between sleep aids and dementia had been reported in earlier studies. And anticholinergic drugs are known to affect cognitive abilities such as attention and working memory in the short term. But this study was larger and more robust, and was the first to show a dose-dependent relationship: taking the drugs for longer periods substantially increased dementia risk. The study is also the first to suggest that adverse effects of using such drugs may persist long after people stop using them, and may not be reversible. The findings appeared in JAMA Internal Medicine, from the American Medical Association.
For the study, researchers at Group Health and the University of Washington analyzed medical and pharmacy records from 3,434 men and women who were part of the Adult Changes in Thought (ACT) study, an ongoing study of brain aging and dementia in the Seattle area. Participants were 65 or older and free of dementia at the start of the study.
They were evaluated every two years for signs of dementia, over a period of more than seven years. During that time, 797 participants were given a diagnosis of dementia, including 637 with Alzheimer’s disease. Past and present medication use was also closely monitored, including the use of over-the-counter drugs sold in pharmacies.
The researchers found that over all, long-term use of the drugs significantly increased the risk of developing dementia, including Alzheimer’s disease. The study found, for example, that people taking at least 10 milligrams per day of doxepin (Sinequan, a sleep and depression aid), 4 milligrams a day of diphenhydramine (Benadryl, for allergies or sleep), or 5 milligrams a day of oxybutynin (a bladder control drug) for more than three years would be at increased risk for developing dementia.
Instead, Dr. Gray said, patients might substitute other drugs that do not have anticholinergic effects, such as 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.
Patients “should tell their health care providers about all their over-the-counter use,” Dr. Gray said. In addition, “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 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.”
Using such drugs, however, does not mean that you will get Alzheimer’s disease. Surveys suggest that anywhere from 8 percent to 37 percent of Americans take anticholinergic drugs on a regular basis, mostly for such conditions as overactive bladder, seasonal allergies or depression. Most of these people will not develop dementia.
Still, the results of this study clearly indicate that long-term use of these drugs may be detrimental to the brain. One possibility is that ongoing use of anticholinergic drugs results in damage to the brain that is similar to that seen in Alzheimer’s disease. Some of the study participants agreed to have their brains autopsied after their deaths. Researchers plan to study those brains to look for signs of Alzheimer’s disease and to compare them with the brains of participants who did not use these drugs.
Source: Shelly L. Gray, PharmD, MS; Melissa L. Anderson, MS; Sascha Dublin, MD, PhD, et al: “Cumulative Use of Strong Anticholinergic Medications and Incident Dementia: A Prospective Cohort Study.” JAMA Internal Medicine, January 26, 2015