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Polypharmacy and Premature Deaths Especially in Older People

How many pills do you take daily? Anything more than 2 or 3 means you are practicing polypharmacy. Multiple meds could lead to a deadly mix.

Have you been to a doctor’s office or a clinic lately? Chances are very good that a med tech weighed you, measured your blood pressure and took your temperature. This information was entered into a computer. That person probably asked about the medicines and supplements you are taking and checked them off in your electronic medical record. This person is not trained to check for drug interactions. And busy doctors and nurses may not take a lot of time to review your medication list for incompatibilities. Even if you are taking a handful of medications and dietary supplements, such polypharmacy may be overlooked. The result can be catastrophic!

Our Love Affair with Drugs:

An article in JAMA Internal Medicine (July 1, 2024) reveals that all drug trends point up. Since the turn of the 21st century, older people have started taking more medications. Researchers analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2020. At the start of the study, 84% of people over 65 were taking prescription medications in the last month. By the close of the study, that number had risen to 90%.

All you have to do is watch a few minutes of television to realize that Americans take an enormous number of medicines. Commercials promoting drugs for diabetes, ulcerative colitis, rheumatoid arthritis, psoriasis and fibromyalgia are commonplace. Such advertising is very expensive but it is obviously extremely effective.

Be honest now. Have you heard of medications such as Jardiance, Skyrizi, Rinvoq, Dupixent, Mounjaro or Ozempic? Unless you do not watch television, chances are pretty good that you have seen a commecial for one of these prescription drugs.

How Many Pills Do People Actually Swallow?

Experts estimate that 4.9 billion prescriptions will be dispensed this year at retail pharmacies. That does not include medications dispensed in retirement communities or hospitals. It also ignores over-the-counter products and dietary supplements.

Now imagine that many of those amber plastic bottles contain 30 pills, though many prescriptions these days are for three months or 90 pills. If we were to add all those tablets and capsules up, it means that Americans likely swallow far more than 100 billion pills annually.

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We’ve done some crude back-of-the-envelope calculations. Not counting OTC products or dietary supplements, we estimate that each man, woman and child in the U.S. swallows over 400 pills every year. If you just count adults, it’s more like 600 pills a year. We suspect that is a very conservative estimate. We know that there are tens of millions of people who swallow a handful of pills every day!

How many pills do you swallow daily? If you are like a lot of people there is a blood pressure medication (perhaps lisinopril or amlodipine), a statin-type cholesterol-lowering drug (likely atorvastatin), a med to control blood sugar (metformin) and a thyroid booster (levothyroxine). And that doesn’t include a multiple vitamin or an herbal arthritis remedy containing turmeric.

The Polypharmacy Predicament:

The problem with this love affair with drugs is something called polypharmacy. That is the technical term for taking multiple medicines. Polypharmacy has become a huge public health problem.

The article in JAMA Internal Medicine (July 1, 2024) was titled:

“Prescription Medication Use Among Older Adults in the US”

The mean number of medications people are taking has increased. In 1999, 24% of the volunteers in the study were taking multiple medications, known as polypharmacy. By 2020, 43% were included in the polypharmacy category.

The authors of this research letter conclude:

“Medications are crucial for managing illnesses and saving lives but contain risks. Understanding medication patterns can inform prescribing practices to reduce adverse drug events risk and unnecessary polypharmacy, hyper-polypharmacy, and PIMs [potentially inappropriate medications].”

The Negative Consequences of Polypharmacy:

The nonpartisan Lown Insitute has issued a report titled:

“Medication Overload: America’s Other Drug Problem.

How the drive to prescribe is harming older Americans.”

Here are some of the findings:

“Every day, 750 older people living in the United States (age 65 and older) are hospitalized due to serious side effects from one or more medications. Over the last decade, older people sought medical treatment more than 35 million times for adverse drug events, and there were more than 2 million hospital admissions.”

Polypharmacy Outcomes

Did those numbers from the Lown Institute surprise you? Have we become so accustomed to adverse drug reactions that we just take such statistics for granted?

One of the contributors to so many drug complications is the epidemic of polypharmacy.

The Lown report notes that:

“More than four in ten older adults take five or more prescription medications a day, an increase of 300 percent over the past two decades. Nearly 20 percent take ten drugs or more.”

When someone takes that many medicines simultaneously, there is a high probability for drug interactions.

Examples of Dangerous, if Not Deadly, Interactions:

Tens of millions of people take a category of medications for high blood pressure called ACE inhibitors. This includes drugs like benazepril, captopril, enalapril, fosinopril, lisinopril and ramipril.

Such medications interact very badly with a common antibiotic known as co-trimoxazole. The actual ingredients are trimethoprim plus sulfamethoxazole. This combo is often abbreviated as TMP-SMZ or TMP-SMX. You may recognize the brand names Bactrim or Septra. The sulfamethoxazole is a “sulfa” antibiotic.

You can learn more about the nature of this under-appreciated drug interaction at this link.

Medical Mistakes and Deadly Drug Interactions

More information about this and another potentially deadly interaction can be found here:

Blood Pressure Drug Combos That Could Be Lethal

Theory vs. Reality: Polypharmacy in the Real World:

Reading how polypharmacy can be problematic is important. But everything you read above is theoretical. It does not reveal the personal nature of such interactions.

Bill in Katy, Texas had been on an ACE inhibitor for two decades to treat high blood pressure. Then a urologist gave him Bactrim, presumably to treat a urinary tract infection. As mentioned, this combination has killed people:

“I was taking benazepril for twenty years with no problems. Then my urologist gave me a prescription for Bactrim. Not long after I fell down four times.

“I eventually made an appointment with my primary care physician. He was so concerned he personally drove me to a hospital. They kept me for five days. When I was released I had a neurological condition called foot drop. My gait was severely affected for several months.

“I still have difficulty with my balance, even after a lot of physical therapy. I believe the combination of Bactrim and lisinopril caused me harm.”

Erin in San Jose, California may have had a closer call than she realized:

“I had an unusual drug reaction that I am now wondering might have been due to an interaction. I was taking lisinopril for high blood pressure. Then I developed an infection and was given a sulfa drug. I developed horrible vertigo after drinking a cup of coffee.

“I felt so bad I told my husband to call 911. When the ambulance arrived, the medics didn’t seem all that concerned. Nevertheless, they did take me to the hospital. I began to get better shortly after. I’ll never know how close a call I had. Now I tell everyone I am allergic to sulfa drugs. That seemed to be the only thing that changed prior to the attack.”

Symptoms of Too Much Potassium (Hyperkalemia):

It is impossible to prove that Erin had an attack of hyperkalemia (excess potassium) in her body. That is what can happen after combining a medicine like Bactrim (a sulfa drug) with an ACE inhibitor such as lisinopril. When potassium levels get too high, symptoms can include:

  • Irregular heart rhythms (arrhythmias)
  • Fatigue, weakness
  • An odd tingling feeling
  • Nausea
  • Paralysis
  • Cardiac arrest.

When someone dies while taking a dangerous drug combination the cause of death is rarely attributed to the medications.

Here is Janet’s story about her husband’s tragic death.

“My husband experienced cardiac arrest and died twenty days after being prescribed trimethoprim. He had been taking lisinopril to treat hypertension.

“When the doctors performed an autopsy, they concluded that the lining of two heart arteries had fatty deposits and that he had a heart attack. There was nothing in the death certificate about a possible drug interaction. My husband had no prior symptoms of heart trouble.”

Proving that Janet’s husband died from a deadly drug interaction would be hard under any conditions. Cardiac arrest from excessive levels of potassium would be difficult to distinguish from a heart attack. This is exactly the kind of suspicious death the authors of this article in the BMJ (Oct. 30, 2014) describe.

Psych Drugs and Polypharmacy:

A report from the ISMP (Institute for Safe Medication Practices) QuarterWatch (March 27, 2019) analyzed FDA data regarding commonly prescribed pain medicines.

Gabapentin (Neurontin) or pregabalin (Lyrica) are taken by more than 10 million Americans. These drugs are referred to as GABA analogs because they mimic a brain chemical called gamma-aminobutyric acid (GABA).

According to that QuarterWatch report:

“Nearly one-half of GABA analog patients were also taking 10 or more other drugs, increasing the risk of interactions, overdose or inhibiting effects on other needed drugs.”

Many of the people taking gabapentin or pregabalin were also taking opioid pain relievers, antidepressants, sleeping pills or anti-anxiety agents.

Polypharmacy: More Common Than You Imagine!

How does this happen? It’s easier than you might think. Gabapentin comes with a warning about psychological depression and/or suicidal thoughts or behaviors. In theory, patients who develop depression while taking gabapentin should be gradually phased off the drug. Instead, though, many appear to be put on antidepressant medications.

Some antidepressants such as bupropion, fluoxetine or sertraline can cause insomnia as a side effect. To solve that problem a doctor might prescribe a sleeping pill like zolpidem (Ambien). In almost the blink of an eye a patient suffering from nerve pain is on three different medications that all affect the brain and could lead to confusion, dizziness and memory impairment. Some people experience heartburn while taking zolpidem. They may get a prescription for omeprazole or self-medicate with Prilosec OTC or Nexium 24HR.

The Lown Institute concludes its report with a stern warning:

“If nothing is done to change current practices, medication overload will lead to the premature deaths of at least 150,000 older people in the U.S. over the next decade, and it will reduce the quality of life for millions more.”

Polypharmacy is not just an older person’s problem. Anyone taking a bunch of pills is vulnerable. A young woman taking a migraine medicine, an antidepressant, birth control pills and a diarrhea drug could just as easily get into trouble as a 74-year-old man taking medications for high cholesterol, hypertension and diabetes.

To combat the problems of polypharmacy, physicians, pharmacists, patients and family members will need to be far more vigilant. We need to combat the message that “more is better.” Less may be best when it comes to drugs!

info iconMedical Consensus Advisory

Everyone agrees that polypharmacy and drug interactions are a huge public health problem. There is no consensus, however, about how to solve the problem. Many experts think that technology will be the answer. But even with electronic health records firmly in place the problem has only gotten worse. Deprescribing is a movement that is growing, but it has not yet been implemented in a systematic way. There is much yet to be done.

Protect yourself and those you love by reading the chapter “Drug Interactions Can be Deadly” in our book Top Screwups. We include detailed protective measures you can take with our “Top 11 Tips for Preventing Dangerous Drug Interactions.” Here is a link to our bookstore.

If you have friends or relatives who are over 65, please share this article and suggest they might like to sign up for our free newsletter at this link. We would like to read your story about polypharmacy in the comment section below.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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  • “Medication Overload: America’s Other Drug Problem. How the drive to prescribe is harming older Americans.” The Lown Institute: https://lowninstitute.org
  • Fralick, M., et al., "Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study," BMJ, Oct. 30, 2014, doi: https://doi.org/10.1136/bmj.g6196
  • Innes, G.K., et al, "Prescription Medication Use Among Older Adults in the US," JAMA Internal Medicine, July 1, 2024, DOI: 10.1001/jamainternmed.2024.2781
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