Is That A New Condition, Or The Last Prescription? 78 Studies Found The Pattern

A drug causes a side effect. The side effect looks like a new problem. The new problem gets its own prescription. Nobody ever goes back and asks whether the first drug caused it.

That is a prescribing cascade, and it is the most ordinary way a person ends up on nine medications without anyone ever deciding they should be.

The pattern has a name and a count

The term was named in a 1997 BMJ review on optimising drug treatment for elderly people (Rochon and Gurwitz, BMJ, 1997). PubMed carries no abstract for it, so we cite it for the concept it introduced and nothing more.

Twenty-five years later, somebody counted. A systematic review searched for published prescribing cascades in community-dwelling adults and included 101 studies, reported across 103 publications, with sample sizes ranging from 126 people to over 11.5 million (Doherty et al., Pharmacology Research and Perspectives, 2022).

Seventy-eight of the 101 studies reported a potential prescribing cascade.

The most frequently identified ones are worth reading slowly, because each one is a plausible medical story that happens to be wrong:

The first drug	The side effect it can cause	The drug added to treat it
Calcium channel blocker	Ankle swelling	Loop diuretic
Amiodarone	Thyroid suppression	Levothyroxine
Inhaled corticosteroid	Oral or skin fungal overgrowth	Topical antifungal
Antipsychotic	Tremor and stiffness	Anti-Parkinson drug
Acetylcholinesterase inhibitor	Urinary urgency	Incontinence drug

Look at the first row. A blood pressure drug causes fluid to pool in the ankles. Swollen ankles look like a fluid problem. A water tablet is a reasonable response to a fluid problem. Every step is defensible, and the patient now takes two drugs where the right move was to change the first one.

The review also found the timing: identified cascades occurred within three months to one year of the initial medication.

ADRs should be included in the differential diagnosis for patients presenting with new symptoms, particularly older adults and those who started a new medication in the preceding 12 months.

Doherty et al., Pharmacology Research and Perspectives, 2022

The move nobody usually offers you

A second review, published a year later, went looking for the same pattern and for what the literature says to do about it. Across 95 publications it identified 115 prescribing cascades where the adverse drug reaction driving the cascade was confirmed (Adrien et al., Drugs and Aging, 2023).

Two numbers inside that are worth pulling out. For 52 of the 115, the literature carried either dose-dependency information or an actual recommendation for what to do instead. And dose dependency was confirmed for 12 of them, meaning the side effect got worse with more drug and better with less.

That second number is the interesting one, because it points at a third option that rarely gets put on the table. If a side effect tracks the dose, then lowering the dose is a candidate fix, and so is swapping to a drug in the same class that does not cause it. Neither of those adds a pill.

The review gives a clean example. Metoclopramide, a nausea drug, can cause extrapyramidal symptoms: tremor, stiffness, restless movement. The cascade response is to add a drug for the movement problem. The alternative the literature records is switching to ondansetron or granisetron, which treat the same nausea without that effect.

So the question to bring to a prescriber is not “should I stop this”. It is “is there a lower dose, or a cousin of this drug, that does not do the thing we are now treating?” That is a question a prescriber can answer in one appointment, and it is not a question most people know exists.

Something can actually be done, and it was tested

This is not just a diagnosis of a problem. There is a randomized trial of a fix, and it is unusually simple.

D-PRESCRIBE recruited 69 community pharmacies in Quebec and cluster-randomised them. Patients were adults 65 and over taking one of four medication classes flagged as potentially inappropriate: sedative-hypnotics, first-generation antihistamines, glyburide, or NSAIDs. 489 patients, mean age 75, 66% women (Martin et al., JAMA, 2018).

The intervention was two pieces of paper. Pharmacists sent the patient an educational deprescribing brochure, and sent the physician an evidence-based pharmaceutical opinion recommending deprescribing.

At six months:

• 106 of 248 (43%) in the intervention group no longer filled the inappropriate prescription
• 29 of 241 (12%) in the usual care group
• Risk difference 31 percentage points (95% CI 23 to 38)

Broken down: sedative-hypnotics 43.2% against 9.0%. NSAIDs 57.6% against 21.7%. Glyburide 30.6% against 13.8%.

A brochure and a letter moved four in ten people off a drug that should not have been there. That is a larger effect than most drugs produce.

The part that keeps this honest

The same trial reports something we are not going to skip past, because it is the exact reason this is a conversation with a prescriber rather than a project you run alone.

Of 77 patients who attempted to taper sedative-hypnotics, 29 (38%) reported withdrawal symptoms.

No adverse events required hospitalisation. But nearly four in ten people felt something real on the way down, from a class of drug they were told was helping them sleep.

That is the whole argument for doing this deliberately. Stopping is often right. Stopping abruptly, alone, without knowing what the first fortnight feels like, is how people conclude they needed the drug after all. We wrote the full version of that problem in the rebound effect.

The list that already exists

There is a published, regularly updated list of medications generally best avoided in adults 65 and over: the American Geriatrics Society Beers Criteria, most recently updated in 2023 (2023 American Geriatrics Society Beers Criteria Update Expert Panel, Journal of the American Geriatrics Society, 2023).

It applies to adults 65 and over in every care setting except hospice and end-of-life care, and the panel is explicit about what it is for: it supports, rather than replaces, shared clinical decision-making. It is a prompt for a conversation, not a prohibition, and that is the panel’s own wording rather than a softening we added.

Its existence is the useful fact here. The question “should somebody my age still be on this?” is not an awkward one invented by the internet. It is a question with an official reference list behind it, maintained by geriatricians, which your prescriber can look at with you.

Prescribing in older adults also differs by sex and gender, and women, who make up the majority of this age group, carry the greatest risk of drug-related harm (Rochon et al., The Lancet Healthy Longevity, 2021).

What we are and are not saying

Claim	Our line
We tell anyone to stop a prescription	Never
Prescribing cascades are documented	Yes. 78 of 101 studies in one review
Every added drug is a cascade	No. Many second drugs are correct
A simple intervention can reverse some of it	Yes. 43% against 12% at six months
Deprescribing is risk-free	No. 38% reported withdrawal symptoms tapering sedative-hypnotics
There is an official list to check against	Yes. The AGS Beers Criteria
Older adults should be on fewer drugs by default	No. They should be on the right ones, reviewed

Where the design shows up

The body answers every input, including the ones we did not intend.

A drug is a signal sent into a system that does not know it was meant for one organ. The swelling in the ankles is not a malfunction; it is the circulatory system doing exactly what a calcium channel blocker tells it to do. The tremor is the nervous system responding correctly to a drug that blocks dopamine.

So the symptom is information. It is the body reporting, accurately, what has been done to it. A cascade is what happens when that report gets filed as a new complaint instead of as a reply.

Which is why the first question about any new symptom in the twelve months after a new prescription is not what else should we add. It is what did we just change.

“The one who states his case first seems right, until the other comes and examines him.” Proverbs 18:17, NASB

The verse carries the conviction. One hundred and one studies carry the pattern.

What to do this week

Write the list out, with dates. Every prescription, every supplement, every over-the-counter thing, and roughly when each one started. The same list does a second job in hospital, where medication is the largest single category of adverse events, and we set out what to put on it in the card we would carry. Most people have never seen their own list on one page, and prescribers rarely see it either, because the items came from different places.

Then look for the sequences. Did anything new start in the twelve months after something else did? That is the window the review identified, and it is the question that finds cascades.

Take the list to one appointment whose only purpose is reviewing it. Not a visit about something else, with the list raised at the end. A review, booked as a review. Ask of each item: what is this for, what happens if it stops, and is it on the Beers list.

Then ask the dose question about any pair you found. If one drug looks like it is treating something a previous drug caused, the useful question is whether a lower dose or a different drug in the same family avoids the problem. That was documented for 52 of the 115 cascades in the Adrien review, and it is the option that does not involve stopping anything cold.

And do not taper anything on your own, particularly sleep or anxiety medication. Four in ten people in that trial felt withdrawal doing it with support.

Read this next: the list to carry into a hospital stay, and how strong the evidence behind it is: nearly 1 in 4 hospital stays had an adverse event. Why the famous medical-error death toll does not survive scrutiny: one Johns Hopkins estimate ranks this killer third. What withdrawal actually is, and why it gets misread as the illness returning: the rebound effect. And how a drug’s benefit gets quoted to you: your statin’s benefit was quoted as a percentage.

Sources

1. Doherty AS, Shahid F, Moriarty F, et al. “Prescribing cascades in community-dwelling adults: A systematic review.” Pharmacology Research and Perspectives, 2022;10(5):e01008. https://pubmed.ncbi.nlm.nih.gov/36123967/
2. Martin P, Tamblyn R, Benedetti A, Ahmed S, Tannenbaum C. “Effect of a Pharmacist-Led Educational Intervention on Inappropriate Medication Prescriptions in Older Adults: The D-PRESCRIBE Randomized Clinical Trial.” JAMA, 2018;320(18):1889-1898. https://pubmed.ncbi.nlm.nih.gov/30422193/
3. Rochon PA, Petrovic M, Cherubini A, et al. “Polypharmacy, inappropriate prescribing, and deprescribing in older people: through a sex and gender lens.” The Lancet Healthy Longevity, 2021;2(5):e290-e300. https://pubmed.ncbi.nlm.nih.gov/36098136/
4. Rochon PA, Gurwitz JH. “Optimising drug treatment for elderly people: the prescribing cascade.” BMJ, 1997;315(7115):1096-1099. https://pubmed.ncbi.nlm.nih.gov/9366745/
5. Adrien O, Mohammad AK, Hugtenburg JG, et al. “Prescribing Cascades with Recommendations to Prevent or Reverse Them: A Systematic Review.” Drugs and Aging, 2023;40(12):1085-1100. https://pubmed.ncbi.nlm.nih.gov/37863868/
6. 2023 American Geriatrics Society Beers Criteria Update Expert Panel. “American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults.” Journal of the American Geriatrics Society, 2023;71(7):2052-2081. https://pubmed.ncbi.nlm.nih.gov/37139824/

Article metadata retrieved from PubMed. Photograph from Pexels. Scripture quoted from the New American Standard Bible.

Educational content from True Health Solutions. We do not diagnose or prescribe, and nothing here is a substitute for care from someone who knows your history. The body heals. We write about what supports that design.