James Castro & Diana Ng, National Center for Health Research
Many people turn to over-the-counter medicines when they need relief from allergy and cold symptoms. They also turn to them if they have trouble falling or staying asleep. This is concerning since recent studies show that one of the most common of those drugs—Diphenhydramine, the active ingredient in Benadryl—could lead to serious health problems, including dementia.[1,2,3]
Most people who take Benadryl don’t know that the main ingredient is also in many other products. This is because the products use different brand names, such as Tylenol PM, Simply Sleep, Unisom, ZzzQuil, Simply Right Sleep Aid, and Equate Nighttime Sleep Aid.[4] This ingredient is considered to be in two classes of drugs: antihistamines and anticholinergics. Antihistamines are used to treat allergy symptoms such as rashes, runny noses, and sneezing. Anticholinergic drugs, on the other hand, are used for a wider variety of conditions including incontinence, sleep problems, and motion sickness. These drugs work by blocking a chemical called acetylcholine, which sends messages to and from the brain and helps in memory and learning. Since diphenhydramine blocks this chemical, it can make people feel drowsy. For this reason, it is used in many over-the-counter sleeping pills.[4]
We’ve known since 2012 that people who regularly take Benadryl (diphenhydramine) or other sleeping pills to fall and stay asleep are more likely to get cancer. They also tend to die earlier than people who don’t take sleep medication. To learn more about safer alternatives to sleeping pills, click here. A 2015 study, led by a researcher from the University of Washington, found that people who take Benadryl regularly are more likely to develop dementia as they age. Dementia is a type of mental decline associated with older age that leads to problems with thinking and decision-making that interfere with daily life.[5] The study also found that the more frequently a person took these medications, the more likely they were to develop the condition.
Drugs containing diphenhydramine aren’t the only ones linked to an increased risk of dementia. The 2015 study also found an increase in dementia linked to other anticholinergics, such as tricyclic antidepressants, which include Tofranil (Imipramine), Elavil (Amitriptyline), and Sinequan (Doxepin). Other medicines that are considered anticholinergic are those used for overactive bladders such as Toviaz (fesoterodine), Ditropan, Gelnique, and Oxytrol (all with the generic name oxybutynin).[6,7] These are just a few of the many names for these drugs. You can find out whether your medication is anticholinergic by using the ACB calculator at this link. This calculator uses information from UpToDate, which is a reliable resource used by medical professionals.
Since 2015, there have been many studies published looking at whether using anticholinergic drugs increases the chances of developing dementia. In 2021, the well-respected Cochrane Library, which interprets medical research, published a systematic review that summarizes the study results available on the topic. In this review, the researchers looked at the results of 25 different studies involving anticholinergic drugs and dementia and concluded that there is likely a link between the two.[3] Nevertheless, they recommended that more research be done on the subject because some of the studies had missing data or other shortcomings, and some of the study results were inconsistent. For example, several studies seemed to contradict each other on whether Benadryl (diphenhydramine) is as likely to cause dementia as tricyclic antidepressants, overactive bladder medications, and some other types of medications. Three studies found that whether the drug is also a tricyclic antidepressant, an overactive bladder medication, or some other types of medication were more likely to be associated with dementia, [8,9,10] while two other studies found that these different types of medications all have the same impact on dementia.[1,2] However, in the other two studies, the researchers didn’t find a significant difference between any of these drug classes and dementia. These inconsistencies make it difficult to draw conclusions.
Taking Benadryl (diphenhydramine) or other anticholinergic drugs occasionally probably won’t harm you. But, it’s important to remember that according to these studies, the more you take—and this means either the dose or the number of days—the higher your risk of developing dementia. There is no firm answer on how much or how long it takes before these drugs begin to increase the risk of dementia. In one study, the researchers found the link to dementia began when people took over fifty doses a year over the course of eight years.[2] Another study found that the relationship began when people took the medication daily for three years [1]. These differences highlight the need for more research, but the basic finding is the same: People who use these drugs frequently for several years are more likely to develop dementia. Unfortunately, the research shows that the risk of dementia will be increased even if the drug use started and stopped many years before the onset of the symptoms.[1,11,12] For these reasons, it is probably best practice to avoid taking the medication regularly to lower the risk of developing dementia. People who are concerned about anticholinergic drugs and their risk for dementia should consult with their healthcare providers.
Bottom Line
While we can’t be absolutely sure that Benadryl (diphenhydramine) or other anticholinergic drugs cause dementia, there are now multiple studies that suggest that it might. When added to other studies showing a link between diphenhydramine and cancer and earlier death, it certainly raises questions about whether this very common and inexpensive medication, sold in supermarkets and drug stores across the country, is too dangerous to take on a daily basis for more than a few weeks.
All drugs tend to stay inside your body longer as we get older. All patients, and especially those who are 55 or older, may want to avoid regular or long-term use of anticholinergics and sleeping pills. Benadryl is both an anticholinergic and a sleeping pill, so that is of even greater concern.
Many people assume that if a drug is sold without a prescription in your neighborhood store, it is safe for you to take it as often as needed. That is not true, because drugs are not tested for very long-term use before they are allowed to be sold. Whether you have allergy symptoms, trouble falling asleep, a bladder that keeps you running to the bathroom more than you’d like, or even depression, there may be safer ways of coping with or treating the problem. And, the strategies that don’t involve medications are the ones with the least risks. To read more about these strategies, please click here.
All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.
The National Center for Health Research is a nonprofit, nonpartisan research, education and advocacy organization that analyzes and explains the latest medical research and speaks out on policies and programs. We do not accept funding from pharmaceutical companies or medical device manufacturers. Find out how you can support us here.
- Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Internal Medicine. 2015;175(3):401-407. https://jamanetwork.com/
journals/jamainternalmedicine/ fullarticle/2091745 - Joung KI, Kim S, Cho YH, Cho SI. Association of Anticholinergic Use with Incidence of Alzheimer’s Disease: Population-based Cohort Study. Sci Rep. 2019;9(1):6802. Published 2019 May 1. doi:10.1038/s41598-019-43066-0
- Taylor-Rowan M, Edwards S, Noel-Storr AH, et al. Anticholinergic burden (prognostic factor) for prediction of dementia or cognitive decline in older adults with no known cognitive syndrome. Cochrane Database Syst Rev. 2021;5(5):CD013540. Published 2021 May 5. doi:10.1002/14651858.CD013540.
pub2 - Diphenhydramine. MedlinePlus. http://www.nlm.nih.gov/
medlineplus/druginfo/meds/ a682539.html#brand-name-1. Accessed June 13, 2022. - Gray SL, Hanlon JT. Anticholinergic medication use and dementia: latest evidence and clinical implications. Ther Adv Drug Saf. 2016;7(5):217-224. doi:10.1177/2042098616658399
- Tricyclic antidepressants (TCAS). Mayo Clinic. https://www.mayoclinic.org/
diseases-conditions/ depression/in-depth/ antidepressants/art-20046983. Published March 30, 2022. Accessed June 13, 2022. - Anticholinergics for Urinary Incontinence in Women. WebMD. http://www.webmd.com/urinary-
incontinence-oab/ anticholinergic-medications- for-urinary-incontinence-in- women. Accessed March 30, 2015. - Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. 2019;179(8):1084-1093. doi:10.1001/jamainternmed.
2019.0677 - Hafdi M, Hoevenaar-Blom MP, Beishuizen CRL, Moll van Charante EP, Richard E, van Gool WA. Association of Benzodiazepine and Anticholinergic Drug Usage With Incident Dementia: A Prospective Cohort Study of Community-Dwelling Older Adults. J Am Med Dir Assoc. 2020;21(2):188-193.e3. doi:10.1016/j.jamda.2019.05.
010 - Richardson K, Fox C, Maidment I, Steel N, Loke Y K, Arthur A et al. Anticholinergic drugs and risk of dementia: case-control study BMJ 2018; 361 :k1315 doi:10.1136/bmj.k1315
- Kersten H, Molden E, Tolo IK, Skovlund E, Engedal K, Wyller TB. Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2013;68(3):271-278. doi:10.1093/gerona/gls176
- Pieper NT, Grossi CM, Chan WY, et al. Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis. Age Ageing. 2020;49(6):939-947. doi:10.1093/ageing/afaa090