One long-ago summer, I joined the legion of teens helping harvest our
valley’s peach crop in western Colorado. My job was to select the best
peaches from a bin, wrap each one in tissue, and pack it into a shipping
crate. The peach fuzz that coated every surface of the packing shed
made my nose stream and my eyelids swell. When I came home after my
first day on the job, my mother was so alarmed she called the family
doctor. Soon the druggist was at the door with a vial of Benadryl
(diphenhydramine) tablets. The next morning I was back to normal and
back on the job. Weeks later, when I collected my pay (including the
½-cent-per-crate bonus for staying until the end of the harvest), I
thanked Benadryl.
Today, I’m thankful my need for that drug lasted only a few weeks. A report published online this week in JAMA Internal Medicine offers compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia.
Anticholinergic drugs block the action of acetylcholine. This
substance transmits messages in the nervous system. In the brain,
acetylcholine is involved in learning and memory. In the rest of the
body, it stimulates muscle contractions. Anticholinergic drugs include
some antihistamines, tricyclic antidepressants, medications to control
overactive bladder, and drugs to relieve the symptoms of Parkinson’s
disease.
What the study found
A team led by Shelley Gray, a pharmacist at the University of
Washington’s School of Pharmacy, tracked nearly 3,500 men and women ages
65 and older who took part in Adult Changes in Thought (ACT), a
long-term study conducted by the University of Washington and Group
Health, a Seattle healthcare system. They used Group Health’s pharmacy
records to determine all the drugs, both prescription and
over-the-counter, that each participant took the 10 years before
starting the study. Participants’ health was tracked for an average of
seven years. During that time, 800 of the volunteers developed dementia.
When the researchers examined the use of anticholinergic drugs, they
found that people who used these drugs were more likely to have
developed dementia as those who didn’t use them. Moreover, dementia risk
increased along with the cumulative dose. Taking an anticholinergic for
the equivalent of three years or more was associated with a 54% higher
dementia risk than taking the same dose for three months or less.
The ACT results add to mounting evidence that anticholinergics aren’t
drugs to take long-term if you want to keep a clear head, and keep your
head clear into old age. The body’s production of acetylcholine
diminishes with age, so blocking its effects can deliver a double whammy
to older people. It’s not surprising that problems with short-term
memory, reasoning, and confusion lead the list of anticholinergic side
effects, which also include drowsiness, dry mouth, urine retention, and
constipation.
The University of Washington study is the first to include
nonprescription drugs. It is also the first to eliminate the possibility
that people were taking a tricyclic antidepressant to alleviate early
symptoms of undiagnosed dementia; the risk associated with bladder
medications was just as high.
“This study is another reminder to periodically evaluate all of the
drugs you’re taking. Look at each one to determine if it’s really
helping,” says Dr. Sarah Berry, a geriatrician and assistant professor
of medicine at Harvard Medical School. “For instance, I’ve seen people
who have been on anticholinergic medications for bladder control for
years and they are completely incontinent. These drugs obviously aren’t
helping.”
Many drugs have a stronger effect on older people than younger
people. With age, the kidneys and liver clear drugs more slowly, so drug
levels in the blood remain higher for a longer time. People also gain
fat and lose muscle mass with age, both of which change the way that
drugs are distributed to and broken down in body tissues. In addition,
older people tend to take more prescription and over-the-counter
medications, each of which has the potential to suppress or enhance the
effectiveness of the others.
What should you do?
In 2008, Indiana University School of Medicine geriatrician Malaz Boustani developed the anticholinergic cognitive burden scale,
which ranks these drugs according to the severity of their effects on
the mind. It’s a good idea to steer clear of the drugs with high ACB
scores, meaning those with scores of 3. “There are so many alternatives
to these drugs,” says Dr. Berry. For example, selective serotonin
re-uptake inhibitors (SSRIs) like citalopram (Celexa) or fluoxetine
(Prozac) are good alternatives to tricyclic antidepressants. Newer
antihistamines such as loratadine (Claritin) can replace diphenhydramine
or chlorpheniramine (Chlor-Trimeton). Botox injections and cognitive
behavioral training can alleviate urge incontinence.
One of the best ways to make sure you’re taking the most effective
drugs is to dump all your medications — prescription and nonprescription
— into a bag and bring them to your next appointment with your primary
care doctor.
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