An older adult starts an iron supplement, becomes constipated, and leaves the next appointment with a laxative. Another begins a statin, develops muscle aches, and is prescribed a pain reliever. Each step can look reasonable on its own, but a large new study suggests these sequences are common enough to deserve a closer look.
Published Sept. 10 in The BMJ, the study examined prescription records for 2,297,942 community-dwelling adults ages 66 and older in Ontario, Canada. Researchers tested 65 drug sequences that an international expert panel had previously flagged as potentially inappropriate. Of those, 24 met every threshold the team set for being both common and closely linked in time.
The study identifies patterns across a population, not errors in any one patient's care. Its findings may matter beyond Canada, because every added drug brings new possible side effects, and many older Americans take prescriptions from several clinicians who may not see the full list.
When a Side Effect Looks Like a New Illness
Researchers call this a potentially inappropriate prescribing cascade. It happens when a side effect of one medication is mistaken for a new health problem and treated with a second drug instead of prompting a review of the first.
The research institute's announcement offered a familiar example. Nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used for pain, can raise blood pressure, which may lead to a new blood pressure prescription instead of a second look at the pain medication.
"These sequences of events are common but often missed in clinical practice," said lead author Dr. Paula Rochon, director of research at the Weston and O'Born Centre for Mature Women's Health at Sinai Health in Toronto.
Iron, Statins, and Dementia Drugs Topped the Frequency Rankings
To make the list, a sequence had to clear three bars. The first drug had to be used by at least 5% of the population, at least 1% of new users had to start the second drug within a year, and the second drug had to follow the first far more often than the reverse.
Three sequences stood out for how often they occurred. Among new users, 11.9% of people who started iron supplements were later prescribed a laxative, 10.9% of statin users later received a pain reliever, and 10.3% of people taking cholinesterase inhibitors, a class of dementia drugs, later received a sleep medication.
The strongest timing links told a different story. Corticosteroids followed by antipsychotics had an adjusted sequence ratio of 2.55, meaning the suspected order appeared about two and a half times as often as the reverse after accounting for prescribing trends. Laxatives followed by antidiarrheal drugs came in at 2.53, and dementia drugs followed by anti-nausea medication came in at 2.24.
Heart and blood pressure drugs were the most widely used starting points. Results were similar for men and women, except for antidepressants followed by overactive bladder drugs, a link that held up only in men.
A Pattern Detector, Not a Verdict
This is an observational study of pharmacy records. It shows that certain drugs follow others more often than chance alone would suggest, but it cannot show why any individual prescription was written. The authors describe their statistical method as a useful but relatively crude screening tool, and they note that not every sequence on the list is inappropriate for every patient. In some cases, the first drug is essential and treating its side effect is the right choice.
The study did not include over-the-counter products or chains of more than two drugs, so the true scope of the problem may be larger. It covered only adults 66 and older in one Canadian province. The work was supported by ICES, Ontario's health data institute, and by a Canadian Institutes of Health Research grant, and the authors reported no relevant financial relationships.
A CDC data brief comparing the two countries found broadly similar prescription drug use. In 2015 to 2016, 22.4% of U.S. adults ages 40 to 79 used five or more prescription drugs, compared with 18.8% of Canadian adults in 2016 to 2017. Cholesterol-lowering drugs were the most common type among adults ages 60 to 79 in both countries.
Questions for the Next Medication Review
Risk is highest for older adults with several chronic conditions, people who see multiple prescribers, and families managing care for a relative with dementia. The researchers also noted that older women tend to take more medications and experience more harmful side effects.
A practical first step is a medication list that shows when each drug was started, why, and by whom. Rochon said knowing what medications you take, when they were started, and for what reason is important for spotting possible cascades. Bring vitamins and nonprescription remedies to appointments, too.
When a new symptom appears, ask whether it could be a side effect of something already being taken. No one should stop a prescribed medication without a clinician's guidance, since stopping some drugs abruptly can cause harm. Sudden confusion, fainting, a fall, chest pain, or trouble breathing needs urgent medical attention.
Many Medicare beneficiaries qualify for a free medication review. Under federal rules, Part D plans must offer medication therapy management to enrollees who have multiple chronic conditions, take multiple Part D drugs, and are likely to exceed an annual drug cost threshold. CMS set that threshold at $1,276 for 2026, and it will rise to $1,340 in 2027.
Plans enroll eligible members automatically, but members still need to take part in the review. Medicare open enrollment, which runs from Oct. 15 through Dec. 7, is a good time to call a plan and ask.
The researchers say the list can help doctors, pharmacists, and health systems decide where to look first when reviewing an older adult's medications, and it could form the basis for automated alerts. MedicalDaily will follow any effort to test the list in U.S. patient records.
Key Questions Answered
What is a prescribing cascade?
It happens when a side effect of one medication is mistaken for a new health problem and treated with another drug, rather than prompting a review of the original medication.
What did the study find?
Of 65 sequences flagged by experts, 24 were common and strongly linked in time among 2.3 million older adults in Ontario. The most frequent were iron, followed by laxatives, statins followed by pain relievers, dementia drugs, and sleep medications.
Does this mean these prescriptions were mistakes?
No. The study detects patterns in pharmacy records and cannot show why an individual drug was prescribed. Some sequences are appropriate for a given patient.
Who is most at risk?
Older adults taking several medications, people with multiple chronic conditions, patients who see more than one prescriber, and people with dementia whose symptoms may be hard to interpret.
Should anyone stop a medication after reading this?
No. Changes should be made only with a clinician, because stopping some drugs abruptly can be dangerous.
How can Medicare enrollees get their medications reviewed?
Part D plans must offer free medication therapy management to eligible members with multiple chronic conditions and medications. Enrollees can call their plan to ask whether they qualify.
Does the Canadian finding apply to Americans?
It has not been tested in U.S. records, but CDC data show that prescription drug use in the two countries is broadly similar.
