When older veterans developed leg swelling after starting gabapentin—the United States’ fifth-most-prescribed drug—only about 4 percent of their physicians recognized the medication as the culprit, according to a recent study. The rest prescribed diuretics for what they thought was heart failure or vein problems. Those “water pills” then caused dizziness, dangerous drops in potassium, and depleted sodium levels. Six patients ended up in the emergency room.
This phenomenon is known as the “prescribing cascade”: One drug causes side effects that doctors mistake for a new disease, triggering another prescription that creates its own problems, leaving people trapped in a sea of unnecessary and potentially harmful medications. In many cases, it can be challenging for doctors to determine whether new symptoms stem from a patient’s medications or signal an emerging health issue.
Why Doctors Miss the Connection
Gabapentin is an anti-seizure medication often prescribed for off-label conditions, such as back pain or insomnia. It can cause more than two dozen side effects, including edema, or swelling of the lower legs—a classic sign of heart failure.
“This is unfortunate but an unsurprising finding,” said Dr. Cooper Stone, a clinical assistant professor of psychiatry and behavioral science at the University of Pennsylvania’s Perelman School of Medicine, who was not part of the study. “In my experience, clinicians often are unaware that gabapentinoids can cause peripheral edema or even respiratory depression.”
Although medications such as gabapentin have known side effects, doctors rarely consider this first when a patient experiences new symptoms, noted Aaron Emmel, a pharmacist and board-certified pharmacotherapy specialist who was not involved in the study.
“The knee-jerk reaction is to suspect and seek a diagnosis for a health condition, not a side effect,” Emmel told The Epoch Times.
Other Common Medications That Trigger Cascades
Some prescribing cascades are clinically appropriate. For example, when someone receives an opioid prescription, that person’s doctor should also prescribe a laxative to prevent constipation, Hedva Barenholtz Levy, a pharmacotherapy specialist and geriatric pharmacist with a senior care pharmacy practice in St. Louis, told The Epoch Times.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Over-the-counter NSAIDs such as ibuprofen and naproxen can trigger a prescribing cascade, as they can cause the kidneys to retain sodium and fluids, leading to increased blood pressure. This may result in additional blood pressure medication.
“This is an important concern because NSAIDs are available without a prescription,” Barenholtz Levy said.
Calcium Channel Blockers (Dihydropyridines, Amlodipine)
Prescribed for high blood pressure, these medications can cause swelling in the ankles and legs by dilating small arteries more than veins, allowing fluid to enter surrounding tissues. Like gabapentin, this side effect is often mistaken for a sign of heart failure, typically leading to a new diuretic prescription or a higher dose.
Diuretics
“Water pills” themselves can cause urinary incontinence, or involuntary urination and leakage, because increased urine production may overwhelm the bladder’s capacity. This can prompt a prescription for a drug to manage what doctors think is an overactive bladder.
Cholinesterase Inhibitors
Doctors may prescribe cholinesterase inhibitors, such as donepezil, for people with dementia. These drugs can also cause urinary urgency and incontinence by increasing bladder muscle contractions, which may then result in prescriptions for an overactive bladder.
ACE Inhibitors
Lisinopril, ramipril, and other ACE inhibitors are used to treat high blood pressure and heart conditions. However, they can block specific substances in the airways, which may cause a nonproductive cough without mucus or phlegm. In response, doctors may prescribe cough medicine. Although over-the-counter cough medications are generally safe, they can have side effects such as drowsiness, dizziness, nausea, and restlessness. Prescription cough medicines that contain opioids can cause respiratory depression and put people at risk for dependency.
Bupropion
Bupropion, an antidepressant drug, can cause jitteriness or insomnia if taken at bedtime, which may lead to additional prescriptions for sleep medication. Both prescription and over-the-counter sleep aids can cause daytime drowsiness, sleep-related issues such as sleepwalking, and interactions with other medications.
Albuterol Inhalers
Using an albuterol inhaler too often can cause nervousness, tremors, and insomnia due to the drug’s action on beta-2 receptors in the lungs, which are also present elsewhere in the body, including the nervous system. These symptoms may be mistaken for an anxiety disorder, which can lead a doctor to prescribe anxiety medication instead of addressing the underlying cause.
Antipsychotics
Antipsychotics can cause drug-induced Parkinsonism by disrupting dopamine in the brain, which is vital for controlling movement. Doctors unfamiliar with these medications might misdiagnose the patient with Parkinson’s disease, Stone noted. As a result, the person may receive treatment for Parkinson’s disease when adjusting the dose or changing to another antipsychotic agent would eliminate the symptoms.
How Cascades Can Start
Emmel described a recent experience involving an older family member who was admitted to a rehabilitation hospital after suffering a broken vertebra. Upon entering the facility, she was taking only a few medications for blood pressure and osteoporosis.
During her short hospital stay, she was given a muscle relaxant, opioid pain relievers, an antidepressant, sleep medication, and gabapentin—and was discharged with prescriptions for all of them, Emmel said.
Emmel’s family member also has a history of falling. Each newly prescribed medication is sedating and can raise the risk of falls and fractures, potentially leading to further treatment and more prescription drugs.
In her case, the evidence of benefit for several of the prescribed medications was completely lacking, Emmel said.
How to Protect Yourself
Even people without strong support systems can take steps to reduce the chances of receiving unnecessary or risky medications during their next hospital or doctor visit.
The best thing one can do is keep an up-to-date list of all of one’s prescription and over-the-counter medications, as well as any dietary or herbal supplements, Emmel said. This list should include when each drug was started or changed, who prescribed or recommended it, and any new symptoms or problems that appeared after starting or changing the medication. Each health care provider can then review this list at every visit.
It’s also important to have a pharmacist review the medication list whenever there’s a change, Emmel said. “The pharmacist is the medication expert and may catch issues or opportunities to optimize the regimen that would be missed by other clinicians.”
People can be proactive by learning about the common and potentially serious side effects of their medications and the signs or symptoms to watch for, Barenholtz Levy said. They should also be willing to discuss the benefits and risks of their prescriptions and be open to possibly reducing the dose or stopping a medication before adding a new drug.
“Ask your prescriber if it’s possible that [your symptoms] may be a side effect of the medication,” Stone said. “Any decent provider at that point should be prompted to then verify whether the side effect is a possibility by referencing a drug database.”
If a person experiences a health-related change shortly after starting or adjusting a medication, there’s a distinct possibility that the medication is the culprit, he added.
“However, automatically assuming new symptoms are side effect-related can be dangerous, so ruling out other health conditions is always warranted.”
