Study: 24 Drug Pairings Flagged As Risky For Older Adults

Consider an older patient who gets a steroid prescription to calm inflammation somewhere in the body. If a side effect like confusion or agitation shows up weeks later and gets mistaken for a new illness, a doctor might write a fresh prescription for an antipsychotic instead of questioning the steroid. A massive new Canadian study found this chain reaction, one drug quietly causing a problem later treated as a new illness, produced the strongest signal among 24 risky prescribing patterns in older adults.

Researchers tracked records for more than 2.3 million older adults in Ontario and confirmed the pattern: prescriptions for antipsychotics followed steroids far more often than the reverse order. Antipsychotics carry “important risks” for seniors, the study authors note, which is part of why this pairing topped a list of habits flagged for doctors and health systems to watch.

These findings come from one of the largest efforts yet to measure how often a prescribing cascade, one drug’s side effect being mistaken for a new illness and treated with a second drug, actually shows up in real life. Published in The BMJ, the study examined 65 drug pairings flagged as potentially inappropriate by an international expert panel, then ranked them by how common they were and how strongly one drug preceded the next.

One Missed Side Effect Can Trigger Another Prescription

Doctors have known about this problem for decades, but catching it in the moment is hard, since a single patient’s chart rarely makes the connection obvious. That gap is what this research team set out to close, measuring how often each of 65 known problematic pairings occurred across an entire population, and how strong the link was between the two drugs.

Ontario Records Covered Nearly 2.3 Million Adults

Researchers pulled health records from Ontario, covering independent older adults age 66 and up who were alive as of January 1, 2022. That group totaled 2,297,942 people, 54.3% of them female. Because Ontario runs a public drug program for seniors, researchers could see which medications were dispensed and when.

A 2025 panel of 12 medical specialists from eight countries built the 65-pairing list. For each pairing, the team tracked people who newly started the first drug between January 2022 and December 2023, then checked whether they went on to start the second drug within a year.

Researchers applied three tests to decide which patterns deserved attention: the starting drug had to be prescribed to at least 5% of the population, at least 1% of people who started it had to later start the second drug within a year, and far more people had to receive drug A before drug B than the reverse, evidence of a real pattern rather than coincidence.

Iron to Laxative Topped Incidence Rankings

Heart and blood pressure drugs were by far the most commonly used starting point, prescribed to somewhere between 19% and 66% of the population depending on the specific drug.

Looking at how often one prescription followed another, three pairings stood out. People taking iron supplements were later prescribed a laxative 11.9% of the time. People taking statins, common cholesterol drugs, later got a pain reliever 10.9% of the time. People on dementia medications were later given a sleep medication 10.3% of the time.

Raw frequency isn’t the whole story, though. Looking across all 65 pairings, researchers also measured how strongly the prescription order favored the suspected cascade over the reverse: steroids followed by antipsychotics led with a ratio of 2.55, laxatives followed by anti-diarrhea medication came in at 2.53, and dementia drugs followed by anti-nausea medication at 2.24. In total, 24 of the 65 pairings cleared all three of the study’s benchmarks, prevalence, incidence, and this sequence strength, forming the priority list doctors could act on.

Men and women weren’t always affected the same way. Most of the 24 priority pairings held up similarly for both groups, but one exception stood out: an antidepressant paired with a drug for overactive bladder was strongly linked in men, but not in women.

One Drug Problem Can Snowball Into Bigger Health Risks

Prescribing cascades aren’t just an academic concern. This pattern can add to a patient’s pill burden, make it harder to stick to a routine, and raise the risk of hospital admission, according to the researchers. Many drugs on the list, including steroids, statins, and dementia medications, are used long term, so fresh opportunities for cascades arise as more medications get added over time.

Authors are careful to note that not every cascade on the list is wrong for every patient; some combinations may be appropriate given someone’s health. The list instead offers a starting point for doctors, pharmacists, and health systems reviewing an older patient’s medications, and possibly a foundation for automatic alert systems.

Before a new pill gets added to treat a new symptom, somebody, whether a doctor, a pharmacist, or a family member, should ask whether an existing prescription might already be the cause. That question sounds obvious, but a dataset of nearly 2.3 million people now gives it real weight, especially when a steroid, a statin, or a dementia drug is part of the picture.

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Disclaimer: This article is based on peer-reviewed research and is intended for general informational purposes only. It is not medical advice and should not replace guidance from a qualified doctor or pharmacist. Anyone with questions about their own or a loved one’s medications should speak with a healthcare provider before making changes.

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