Study Flags Potentially Inappropriate Prescribing Cascades Among Seniors

A new study of nearly 2.3 million older adults in Ontario found that a drug’s side effect is often treated as a new disease, and a second drug is added to treat it. The researchers called 24 of these sequences high-priority prescribing cascades. The most common were iron pills followed by laxatives, cholesterol drugs followed by pain relievers, and Alzheimer’s drugs followed by sleeping pills.

The paper was published online September 10 in The BMJ. Paula Rochon of the University of Toronto and Sinai Health led a team that started with 65 drug pairs already flagged as potentially inappropriate. They evaluated Ontario drug records for community-dwelling adults aged 66 or older to determine how common the first drug was, how often the second drug followed, and how tight the timing was.

The cohort was 2,297,942 people, 54.3% women, and 12.8% aged 85 or older. 37% of the list met all three criteria – high initial drug prevalence, high incidence of the prescribing cascade, and high strength of temporal association.

The list of common prescribing cascades shouldn’t be considered a definitive record, lead author Paula Rochon told the Washington Post. Rather, the study’s results should be used to understand that prescribing cascades do occur and are much more likely to happen with older adults. “Older people may be particularly at risk [of inappropriate prescribing] because as you get older, you often develop more chronic conditions and are therefore on more medications.”

According to CDC data, 89.2% of senior citizens aged 65 and older took a prescription drug in the last 12 months. A JAMA study found polypharmacy, concurrent use of five or more medications, increased for senior citizens from 23.6% in 1999-2000 to a peak of 43% in 2017-March 2020. CDC data also show that those taking three or more medications in that age group increased from 59.8% to 67.7% from 2001-2004 to 2017-March 2020. JAMA evaluated data for the past year, while CDC evaluated data for the past 30 days.

Polypharmacy is associated with higher mortality and hospitalization for senior citizens. A 2022 meta-analysis found a 28% higher mortality and 50% higher hospitalization rate, while a UK cohort of individuals over 75 found a 137% higher one-year mortality and 147% higher one-year hospitalization rate.

Rochon termed the “Prescribing cascade” in a paper she co-authored with Jerry Gurwitz in 1997, and it describes something different from a drug interaction. It is not an interaction between two or more medications. Rather, it is a symptom from one medication that is treated as a new diagnosis with a second medication prescribed to treat the new condition.

“The prescribing cascade, whereby additional drug treatment is started after a patient develops an adverse reaction to a drug, is largely preventable by carefully considering whether any new medical condition might be the result of an existing drug treatment,” Rochon and Gurwitz wrote in the 1997 paper. “The prescription of a new drug specifically to treat an adverse drug effect should be considered the choice of last resort in the care of older patients.”

There has been no evaluation of whether prescribing cascades have increased in the nearly 30 years since the term was coined, but there is a significant increase in the number of medications senior citizens are receiving, which makes it more likely for the cascade to begin. Physicians are more likely to diagnose a side effect from a medication as a new condition when the patient is taking multiple drugs at the same time.

Rochon said the cascades are common, but “often missed in clinical practice.” She added, “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.”

Cardiovascular drugs were the most common starting point. Antihypertensives were being taken by 65.9% of the cohort and diuretics by 19%. The pairs with the highest one-year incidence were iron supplements followed by laxatives, at 11.9%; statins followed by pain relievers, at 10.9%; and cholinesterase inhibitors, used in Alzheimer’s disease, followed by sleep drugs, at 10.3%.

For some pairs, the second drug came after the first about two and a half times as often as the first drug came after the second. This was most common when corticosteroids, anti-inflammatory drugs like Prednisone, were followed by antipsychotics and laxatives were followed by antidiarrheal drugs. Cholinesterase inhibitors, Alzheimer’s and dementia drugs, were followed by anti-nausea drugs. One pattern showed up only with men who were on an SSRI or SNRI antidepressant, which was followed by a drug for an overactive bladder.

Rochon said the best way to prevent prescribing cascades is to keep a list of all medications, including dosages and the reason for each one. Over-the-counter medications weren’t included in Rochon’s study, but she said physicians should also include these drugs on the list so they can properly evaluate the patient’s symptoms based on all drugs being taken.

Rochon also encourages patients to ask their physicians questions when a new drug is recommended. Patients should ask the health care provider if the symptom they are attempting to treat could be a side effect of a drug they are currently taking. If the symptom is a side effect of a current drug, physicians could explore alternative options, including a dosage change or safely deprescribing from the drug.