A large study across Ontario has found that widely used medications, including statins and iron supplements, can sometimes trigger a chain of additional prescriptions in older adults. In these cases, a side effect from one drug may be mistaken for a new medical condition, prompting treatment with another medication.
The research, published in BMJ, was led by Dr. Paula Rochon, Director of Research at the Weston and O’Born Center for Mature Women’s Health at Sinai Health in Toronto. The findings suggest that certain combinations of prescriptions represent a common but often overlooked source of drug-related harm across the population. They can also create avoidable costs for the healthcare system.
When a Side Effect Leads to Another Prescription
This pattern is known as a potentially inappropriate prescribing cascade (PIPC). It occurs when a side effect caused by one medication is interpreted as a separate health problem, leading to another prescription that may not have been necessary.
One example identified by the researchers involves non-steroidal anti-inflammatory drugs (NSAIDs), which are commonly used for pain. These medications are associated with increases in blood pressure. If that change is treated as a new case of high blood pressure, a patient may receive another medication instead of having the original pain treatment reconsidered.
Older adults are particularly susceptible because they are more likely to have multiple health conditions and take several medications at the same time. With many drugs involved, it can become difficult for both clinicians and patients to determine whether a new symptom is actually being caused by an existing prescription.
“These sequences of events are common but often missed in clinical practice,” said Dr. Rochon, who holds the Barry J. Goldlist Chair in Aging and Health at Sinai Health and is also a professor of medicine at the University of Toronto. “Knowing what medications you are taking, when they were started, and for what indication is important in order to identify possible prescribing cascades that may be problematic.”
Researchers Identify 24 Common Prescribing Cascades
The project involved an interdisciplinary international group of experts in medication prescribing and geriatric medicine. Collaborators came from the United States, Belgium, Italy, Israel and Ireland. The Sinai Health team included Drs. Vasily Giannakeas, Nathan Stall and Christina Reppas-Rindlisbacher, along with research staff Wei Wu and Joyce Li.
In earlier work, the researchers drew on the expertise of 12 international panelists specializing in internal medicine, geriatric medicine and clinical pharmacology to develop a list of 65 PIPCs.
For the new analysis, that list was compared with population-level prescription data from ICES, Ontario’s health data institute, working with Lavina Matai and Zhiyin Li. The team evaluated each possible cascade using three measures: how frequently the first medication was prescribed, how often a second medication followed it, and how strongly the two prescriptions appeared to be connected.
That process allowed the researchers to identify 24 potentially inappropriate prescribing cascades that were both commonly observed in the population and had the potential to cause harm.
Seeing the Pattern Behind Every Prescription
For Dr. Rochon, the results point to an important communication gap that can develop gradually as medications accumulate.
“Our concern is that so often these conversations between the health care prescriber and the patient are being missed, so people don’t recognize the sequences of events and that they are connected to one another,” she said.
Addressing the problem means looking beyond a simple list of the medications a patient is currently taking. Physicians also need to consider when each drug was introduced, why it was prescribed, and whether a newer medication was added to address a symptom that might actually have been caused by an earlier treatment.
Mature Women May Face Greater Risk
The findings may be especially important for mature women. Over the course of their lives, women tend to experience more chronic conditions than men, receive more drug therapies, and have more adverse drug events.
Taking multiple medications increases the opportunity for a side effect to be misinterpreted as a separate diagnosis. As a result, another drug may be added instead of tracing the symptom back to the medication that caused it.
Technology Could Help Catch Drug Cascades
The researchers say technology could provide one way to reduce these potentially harmful prescribing patterns.
Automated clinical decision support systems could be designed to recognize a possible prescribing cascade as it develops. Such systems might alert clinicians when a new medication appears to be treating a known side effect of an existing drug, giving them an opportunity to reconsider the treatment plan before adding another prescription.
This information could be incorporated into several types of automated tools that alert clinicians to potentially inappropriate prescribing cascades at the point of care.
Pharmacists Could Play a Larger Role
The researchers also see an opportunity to make greater use of pharmacists as part of the healthcare team.
More directly involving pharmacists in prescribing decisions alongside physicians could help uncover medication patterns that might otherwise go unnoticed. Their expertise could help identify potentially inappropriate prescribing cascades that warrant further evaluation.


