If you’re like most Americans, you have probably taken—or may currently take—an over-the-counter (OTC) allergy or cold drug, pain reliever or sleep aid containing diphenhydramine. This generic medication has become widely available without prescription in such products as Benadryl, Excedrin PM and Tylenol PM.

What you may not know: These drugs, as well as dozens of others that are used by millions of Americans, block the action of acetylcholine, a neurotransmitter that controls several critical functions in the body ranging from body secretions to cognitive function.

Why is this a potential problem? Cells in virtually every part of the body have molecular openings (receptors) that respond to acetylcholine. A drug that’s used to treat a condition in one part of the body invariably affects receptors somewhere else. Result: A high incidence of unintended effects. In some cases, people who use these so-called anticholinergic drugs suffer side effects such as constipation, urinary retention, blurred vision and dry mouth, and now researchers say use of these drugs increases risk of Alzheimer’s disease.


Medications that cause a high rate of unintended effects are known in the health-care community as “dirty” drugs. The same active ingredient that reduces bladder spasms, for example, might also cause constipation by reducing intestinal contractions or eye dryness by blocking acetylcholine at the receptors that control body secretions.

Important finding: A study published in JAMA Internal Medicine tracked health outcomes and anticholinergic drug use for 3,434 people age 65 years or older for more than seven years. None of the study participants had dementia at the beginning of the study, but nearly one-quarter developed it during the study period—most in the form of Alzheimer’s disease. Alarmingly, the researchers discovered that the higher the dose of an anticholinergic drug and the longer a person was on it, the higher that person’s risk of dementia. In fact, risk was 54% greater for those taking high doses of anticholinergic drugs for more than three years than for those who did not take such drugs. Specifically, those at risk included people taking at least 10 mg per day of doxepin (Silenor), 4 mg per day of diphenhydramine (Nytol, Benadryl) or 5 mg per day of oxybutynin (Ditropan).


Popular anticholinergic drugs…

• Allergies. Many of the older allergy drugs, including Benadryl, are effective at relieving irritated eyes, sneezing and runny nose. That’s not surprising, since one of the main anticholinergic effects is to reduce mucus and other secretions. But the side effects, such as drowsiness and a dry mouth and eyes, are pronounced. Few can take these drugs and function well the next day.

My advice: Avoid diphenhydramine.

Better: Avoid allergens in the first place. If this is not possible, take a nonsedating antihistamine, such as fexofenadine (Allegra) or loratadine (Claritin). These drugs have relatively mild anticholinergic effects—most people can take them without experiencing side effects. If you have seasonal allergies, see this Daily Health News Guide to Stop Seasonal Allergies—Without Drugs . The researchers advised that, whenever possible, nonanticholinergic medications should be substituted for these drugs.

• Urinary incontinence. People who suffer from an unusually intense and frequent need to urinate, known as urge incontinence, are often treated with overactive bladder medications such as oxybutynin (Ditropan) or tolterodine (Detrol).These drugs may cause dry mouth, blurred vision, constipation and/or cognitive impairments. Adults age 65 and older have the highest risk for side effects. This is partly because the blood-brain barrier becomes more porous with age. These drugs are not supposed to enter the brain—but often do.

My advice: After discussing dosages and potential side effects with your physician, you may want to consider taking one of these drugs if incontinence is preventing you from living a normal life. It may be better to cope with drug side effects than to become housebound due to fear of having an “accident.”

Even better: Bladder training, in which a doctor or therapist teaches you to gradually increase the intervals between urinating by waiting longer than you think you can. Most people can gradually increase their “holding” time by several minutes to several hours. (Also see this Daily Health News guide to what helps with bladder control.)

If urgency/frequency occurs during the night, see your doctor. Nighttime urination may especially be a problem for men with enlarged prostates, but incontinence drugs are unlikely to help—and may even be harmful.

• Depression. Before selective serotonin reuptake inhibitor (SSRI) antidepressants were developed, doctors often prescribed amitriptyline (Elavil) for depression. This drug has fallen out of favor because it tends to cause strong anticholinergic side effects. But some of the newer drugs, such as paroxetine (Paxil), the most anticholinergic of the SSRIs, have similar effects.

My advice: If your doctor is going to prescribe an antidepressant, ask him/her about SSRI antidepressants with the least anticholinergic effects, particularly those with a shorter “half-life,” such as sertraline (Zoloft). These drugs are eliminated from the body more quickly, so they’re less likely to cause side effects. This is particularly important for older adults, who metabolize drugs more slowly.

• Insomnia. Most OTC drugs taken for insomnia, including the allergy medication Benadryl and sleep aid Sominex, contain diphenhydramine. It can cause constipation, difficulty concentrating, urinary retention and trouble with eye focus—and stays active in the body for 12 to 18 hours, which can lead to next-day grogginess.

My advice: Avoid taking diphenhydramine for insomnia.

Better: Practice good sleep habits. Examples: Go to bed at a reasonable hour, and maintain the same schedule every night. Exercise regularly but not within two hours of your bedtime—it will make falling asleep more difficult. Take a warm bath before bed to help you relax.

Important: Make the bedroom a peaceful place—no TV, computer, etc. If you don’t fall asleep within a half hour, get up and do something else until you’re ready to try to sleep again. Avoid the computer and all electronics—their glow delays release of the sleep-inducing hormone melatonin.

• Motion sickness. Many anticholinergic drugs prevent and/or relieve motion sickness. However, the doses needed to reduce motion sickness can also cause drowsiness or confusion as a side effect.

My advice: Avoid motion sickness drugs such as dimenhydrinate (Dramamine).

Better: Use a prescription scopolamine patch (such as Transderm Scop). The active ingredient enters the body slowly and is less likely to cause side effects than oral dimenhydrinate. The patches deliver about 1.5 mg of scopolamine over three days. Apply the patch to a hairless area at least four hours before traveling/sailing. Remove the patch if you notice any of the anticholinergic side effects described above.