A widely available ingredient used in nighttime sleep aids, allergy tablets and “PM” pain relievers has been associated with a higher risk of dementia when taken repeatedly over long periods.
The ingredient is diphenhydramine, a sedating first-generation antihistamine best known as the active drug in Benadryl. It is also included in numerous over-the-counter products marketed for occasional sleeplessness. A related antihistamine, doxylamine, is used in some versions of Unisom and nighttime cold medicines.
The warning does not mean that taking one tablet causes dementia. The most influential research examined the cumulative use of strong anticholinergic medicines across many years, rather than a single dose or one specific brand. It found that older adults with the greatest overall exposure had a substantially higher rate of dementia than people who had not used these drugs.
Because the study was observational, it cannot prove that the medicines directly caused dementia. Even so, the findings support existing clinical guidance that older adults generally should not use sedating antihistamines as routine sleep treatments.
Why Diphenhydramine Makes People Sleepy
Diphenhydramine was developed as an antihistamine for allergy symptoms. It blocks histamine, a chemical involved in allergic reactions but also in maintaining alertness. Because the drug readily enters the brain, drowsiness is a common effect.
Manufacturers use that sedating effect in nonprescription nighttime sleep products. Diphenhydramine may also appear in combination products containing acetaminophen or another pain reliever, meaning someone may take it without immediately recognising that the “PM” ingredient is an antihistamine.
Diphenhydramine also has strong anticholinergic properties. It blocks the action of acetylcholine, a neurotransmitter involved in attention, learning, memory, muscle activity and numerous automatic bodily functions.
That activity can cause dry mouth, constipation, blurred vision, urinary difficulty, confusion and next-day grogginess. MedlinePlus states that diphenhydramine generally should not be used by older adults except in circumstances such as managing a serious allergic reaction, because other medicines may be safer or more effective.
What the Dementia Study Actually Found
The major study behind the warning was published in JAMA Internal Medicine and included 3,434 adults aged 65 or older who did not have dementia when they entered the research programme.
Researchers reviewed pharmacy records to estimate each participant’s exposure to strong anticholinergic medicines during the previous ten years. The most frequently used categories included first-generation antihistamines, tricyclic antidepressants and drugs prescribed for bladder problems.
Participants were followed for an average of 7.3 years. During that time, 797 developed dementia, including 637 who developed Alzheimer’s disease. The researchers identified a dose-response pattern: dementia risk generally increased as cumulative anticholinergic exposure increased.
Compared with people who had no recorded exposure, those in the highest category had an adjusted hazard ratio of 1.54 for dementia. That corresponds to a 54 percent higher relative rate, not a guarantee that 54 percent of users will develop the condition.
The highest exposure category represented more than 1,095 standardised daily doses over ten years. At a minimum effective daily dose, that could approximate taking a strong anticholinergic every day for more than three years.
The Study Was About Anticholinergic Burden, Not Only Sleeping Pills
The results are sometimes simplified into claims that Benadryl or an OTC sleep aid “causes Alzheimer’s.” That wording goes further than the evidence permits.
Researchers assessed the combined burden of numerous strong anticholinergic drugs. These included medicines used for allergies, depression, overactive bladder, nausea and other conditions. Diphenhydramine belongs to the relevant drug class, but the study did not isolate it and prove that it independently caused each dementia case.
The researchers also relied on dispensing records. A filled prescription or recorded pharmacy purchase does not prove that every dose was taken. Some first-generation antihistamines are bought from shops outside healthcare systems, so exposure may also have been undercounted.
Additionally, insomnia can sometimes precede cognitive decline. People in the early, undiagnosed stages of a neurological condition might begin using more sleep medication, making it difficult to separate cause from early symptom.
The research team tried to reduce that problem by excluding medication use during the most recent year before each dementia assessment and by conducting additional analyses. The association remained, but observational evidence still cannot establish causation as confidently as a randomised clinical trial.
Why Older Adults Face Greater Immediate Risks
The dementia association concerns long-term exposure, but sedating antihistamines can create more immediate problems.
As people age, their bodies may process medicines more slowly, and the brain may become more sensitive to anticholinergic effects. A dose that produces manageable drowsiness in a younger adult may cause pronounced confusion, poor balance or prolonged sedation in someone older.
These effects can contribute to falls, driving impairment, urinary retention and delirium. They can become more intense when diphenhydramine is combined with alcohol, prescription sedatives, anti-anxiety drugs, opioid pain medicines or other products containing antihistamines.
Doxylamine presents similar concerns. MedlinePlus states that adults aged 65 and older generally should not take doxylamine because it may be less safe or effective than alternative treatments.
The 2023 American Geriatrics Society Beers Criteria identifies potentially inappropriate medicines for older adults and continues to highlight strong anticholinergic exposure as an important medication-safety concern.
OTC Availability Does Not Mean a Product Is Suitable for Nightly Use
One reason these medicines remain popular is their accessibility. They can be purchased without an appointment and may create noticeable drowsiness within a relatively short time.
However, a medicine’s nonprescription status does not mean it is intended for indefinite nightly use. OTC products are generally designed for occasional, short-term symptoms and can still cause interactions or serious side effects.
Tolerance to the sedating effect may also develop. The initial dose becomes less effective, encouraging some people to take the medicine more frequently or increase the amount. That raises the cumulative anticholinergic burden without necessarily resolving the underlying cause of insomnia.
The American Academy of Sleep Medicine recommends against using diphenhydramine to treat chronic sleep-onset or sleep-maintenance insomnia. Its evidence review found limited support for meaningful benefit and concluded that the balance between benefits and harms did not justify routine use.
Poor Sleep Also Deserves Medical Attention
Avoiding one sleep aid does not mean chronic insomnia should be ignored. Persistent sleep problems are themselves associated with impaired concentration, mood difficulties, accidents and poorer health.
Insomnia may be related to pain, depression, anxiety, medication side effects, sleep apnea, restless legs syndrome, nighttime urination or an inconsistent sleep schedule. Treating the underlying cause is more useful than repeatedly suppressing wakefulness with a sedating antihistamine.
Poor sleep and dementia also have a complicated two-way relationship. The National Institute on Aging reports that inadequate or disrupted sleep may contribute to cognitive decline, while early brain changes may also disturb normal sleep.
This complexity is another reason the research should not be interpreted as a choice between taking a pill and remaining awake indefinitely. The safer approach is to identify why sleep is failing and select treatment based on that cause.
The Preferred Long-Term Treatment Does Not Begin With a Pill
For chronic insomnia, the American College of Physicians recommends cognitive behavioural therapy for insomnia, known as CBT-I, as the initial treatment.
CBT-I combines methods such as stimulus control, carefully managed sleep scheduling, cognitive therapy and education about sleep habits. It aims to change the behavioural and psychological patterns that keep insomnia active rather than producing temporary sedation.
The ACP notes that CBT-I can be delivered individually, in groups, by telephone or through structured online programmes. When it does not provide sufficient improvement, a clinician and patient can discuss whether medication should be added after weighing its benefits, risks and cost.
Medication may still be appropriate in selected situations. The choice depends on the type of sleep problem, other medical conditions, current prescriptions and the person’s risk of falls or cognitive side effects.
Older Adults Should Review the Active Ingredient
Someone using an OTC sleep product should check the “Drug Facts” panel rather than relying only on the brand name. Similar brand families may sell multiple formulations with completely different ingredients.
Products listing diphenhydramine, doxylamine or another first-generation antihistamine deserve particular attention when they are being used regularly by someone aged 65 or older.
A person taking these products nightly should not panic over past use. The association does not mean dementia is inevitable, and the research does not provide an individual prediction. It does provide a reason to discuss the medicine with a doctor or pharmacist and review the total anticholinergic burden created by all prescription and nonprescription drugs.
A medication should not be stopped or replaced solely because of an alarming headline, especially when it is treating allergies, severe itching or another medical problem. A professional review can identify the original reason for use, determine whether it is still necessary and select a safer alternative when appropriate.
The central message is not that one occasional sleeping pill permanently damages the brain. It is that long-term, repeated exposure to strong anticholinergic medicines may carry risks that are easy to overlook when the product comes from a supermarket or pharmacy shelf.
