Five drug categories consistently flagged as risky for adults 65 and older are benzodiazepines, first-generation antihistamines, long-term NSAIDs, certain diabetes medications called sulfonylureas, and antipsychotics. These aren’t obscure prescriptions. Many are available over the counter or prescribed routinely, which is exactly why they’re worth knowing about. The American Geriatrics Society maintains a list called the Beers Criteria, updated regularly, that identifies dozens of medications considered potentially inappropriate for older adults. The five below are among the most commonly used and most likely to cause serious harm.
Why Medications Hit Harder After 65
Before getting to the specific drugs, it helps to understand why aging changes the equation. After age 40, the liver’s ability to process medications before they enter the bloodstream declines by roughly 1% per year. That means a standard dose can produce higher drug concentrations in an older person than the same dose in a younger one. The kidneys slow down too: filtration rate drops an average of 8 mL/min per decade after 40, so drugs that depend on the kidneys for clearance linger in the body longer.
What makes this particularly tricky is that standard blood tests can miss the problem. Creatinine levels, the usual marker for kidney function, often look normal in older adults because they have less muscle mass and produce less creatinine in the first place. A doctor may see a normal lab result and assume the kidneys are handling a medication just fine when they’re not.
Benzodiazepines and Sleep Medications
Benzodiazepines like alprazolam (Xanax), lorazepam (Ativan), and diazepam (Valium) are prescribed for anxiety, insomnia, and muscle spasms. In older adults, they significantly increase the risk of falls, hip fractures, confusion, and car accidents. The sedation they cause is stronger and lasts longer because the aging liver clears these drugs more slowly, and the brain becomes more sensitive to their effects.
The related “Z-drugs” used for sleep, such as zolpidem (Ambien), eszopiclone (Lunesta), and zaleplon (Sonata), carry similar risks and are also on the Beers Criteria list. They cause many of the same problems: next-day drowsiness, unsteady walking, and impaired thinking.
For insomnia, cognitive behavioral therapy (often called CBT-I) is considered the gold standard for older adults. It combines sleep hygiene education, relaxation techniques, and structured changes to sleep habits. When medication is needed, melatonin, ramelteon, or newer sleep drugs called dual orexin receptor antagonists (suvorexant, lemborexant) are generally considered safer options with fewer next-day effects.
First-Generation Antihistamines
Diphenhydramine, the active ingredient in Benadryl and many over-the-counter sleep aids like Tylenol PM, is one of the most widely used medications that older adults should avoid. It belongs to a class of drugs called anticholinergics, which block a chemical messenger called acetylcholine. In the brain, acetylcholine plays a central role in learning and memory. The body’s natural production of this chemical already declines with age, so blocking what’s left creates what researchers describe as a “double whammy” for older people.
The result is a cluster of problems: short-term memory loss, confusion, dry mouth, constipation, blurred vision, difficulty urinating, and increased fall risk. A study highlighted by Harvard Health found that regular use of anticholinergic drugs is linked to increased dementia risk. Other first-generation antihistamines on the avoid list include chlorpheniramine, doxylamine (found in NyQuil), hydroxyzine, and meclizine. For allergies, newer antihistamines like cetirizine (Zyrtec) or loratadine (Claritin) are far less likely to cause these problems because they don’t cross into the brain as readily.
NSAIDs for Chronic Pain
Ibuprofen (Advil, Motrin), naproxen (Aleve), and other non-steroidal anti-inflammatory drugs are so common that many people don’t think of them as risky. For occasional use in younger adults, they’re generally fine. But in older adults, chronic NSAID use raises the risk of gastrointestinal bleeding, kidney damage, elevated blood pressure, and worsening of heart failure. The Beers Criteria flags all non-selective oral NSAIDs, with special warnings for indomethacin and ketorolac as the highest-risk options.
The kidney concern is particularly relevant. Since kidney filtration is already reduced with age, adding a drug that further restricts blood flow to the kidneys can tip someone from stable, mildly reduced function into acute kidney injury. This can happen even with short courses of these medications, especially if the person is also taking a blood pressure drug or diuretic.
For chronic pain management in older adults, acetaminophen (Tylenol) at appropriate doses is typically the first option. Topical NSAIDs, like diclofenac gel applied directly to a sore joint, deliver anti-inflammatory effects locally with far less systemic absorption. Physical therapy, heat, and gentle exercise also play a meaningful role.
Sulfonylureas for Diabetes
Sulfonylureas are oral diabetes medications that lower blood sugar by stimulating the pancreas to release more insulin. The problem for older adults is that they can push blood sugar too low, causing hypoglycemia. Severe hypoglycemia in a 75-year-old can cause confusion, falls, seizures, and cardiac events, and the symptoms can easily be mistaken for a stroke or dementia episode.
Glyburide (also known as glibenclamide) is the worst offender in this class. In a study of patients 65 and older, 42% of those taking glyburide experienced at least one hypoglycemic episode over 12 weeks, compared with 26% on a shorter-acting alternative. A large four-year study of nearly 20,000 older patients found glyburide had the highest incidence of severe hypoglycemia among all sulfonylureas tested. Most hypoglycemic episodes in patients over 75 occurred soon after starting treatment, making the first few weeks especially dangerous.
The Beers Criteria flags all sulfonylureas for older adults, not just glyburide. Newer diabetes drug classes, like metformin or certain incretin-based therapies, offer blood sugar control with a much lower risk of dangerous lows.
Antipsychotics
Both older (typical) and newer (atypical) antipsychotic medications carry serious risks for older adults, particularly those with dementia. These drugs are sometimes prescribed to manage agitation, aggression, or hallucinations in people with Alzheimer’s disease or other forms of dementia. Regulatory agencies in the US, UK, and Europe have issued warnings based on evidence of increased risks for stroke and death when antipsychotics are used to treat behavioral symptoms of dementia.
Beyond the mortality risk, antipsychotics cause sedation, movement problems similar to Parkinson’s disease, metabolic changes, and an increased risk of falls. In older adults without dementia, they’re also flagged on the Beers Criteria due to these same side effects.
Managing agitation or behavioral changes in dementia is genuinely difficult, and sometimes there are no perfect alternatives. Non-drug approaches, including structured routines, reducing environmental overstimulation, music therapy, and caregiver training, are recommended as first-line strategies. When these aren’t enough and safety is at stake, the decision to use an antipsychotic should involve careful weighing of the specific risks for that individual.
How to Use This Information
If you or someone you care for is taking one of these medications, don’t stop it abruptly. Suddenly discontinuing benzodiazepines, for example, can cause seizures. The value of this list is as a starting point for a conversation. Bring it to a medication review with a pharmacist or physician, especially after a hospitalization or when seeing a new specialist who may not know the full medication picture.
Polypharmacy, taking five or more medications simultaneously, is common in older adults and compounds these risks. Each additional drug increases the chance of harmful interactions. A medication that was appropriate at 55 may not be appropriate at 75, and a yearly review of every prescription and over-the-counter product is one of the most practical steps you can take to reduce risk.