The prescribing cascade: the error of treating side effects with more drugs

Marta Tello is a 23-year-old pharmacist who works in Algete, in the Madrid region of Spain. Six months ago, while completing her training with a primary care team in Seville, she encountered a clinical case that she says she will remember throughout the professional career she is just beginning: “This person was taking 18 different medications, something striking even for an 80-year-old with multiple underlying conditions. When we reviewed the case, we identified several prescribing cascades that needed to be reassessed,” she says.

The patient had been prescribed an antidepressant (venlafaxine) that at high doses raises blood pressure, for which an antihypertensive had been prescribed. He was also taking hydrocortisone —which can increase blood glucose— so physicians were about to prescribe an antidiabetic. “These cascades occur when a drug’s side effect is treated as if it were a new health problem. Instead of reviewing the prescription that caused the adverse effect, another drug is prescribed that may be unnecessary and could have serious clinical consequences for the patient,” she explains.

A study by Tello on this clinical case received an award at a recent congress of the General Council of Pharmaceutical Associations, held in Oviedo, Spain. The accolade illustrates the growing concern among health professionals, scientific societies and government agencies about therapeutic cascades, a risk that becomes more frequent “as the population ages and chronic health problems —and the medications used to treat them— increase,” says Carlos Fernández Moriano, deputy director of Training and Professional Services at the Council.

Catalonia has now become the first region of Spain to launch a campaign aimed at professionals and the public to raise awareness about a trend that contributes to increasing problems caused by drugs. “Between 5% and 10% of hospitalizations are related to adverse drug reactions, and almost half of these cases could be prevented,” the Catalan Ministry of Health notes.

Periodic review

Anna Coma, head of the Territorial Action Division in the Medication Area of the Catalan Health Service (CatSalut), stresses the importance of a “periodic review” of medication to distinguish between cascades that pose a danger to the patient and those that may be justified. “A typical example is constipation from iron supplements. The doctor already knows this is a common side effect and may also prescribe a laxative if they consider the risk–benefit balance favorable for the patient. What matters is that decisions are based on such assessments and not on a confusion,” she explains.

The awareness campaign materials include about 20 potentially dangerous prescribing cascades. One can occur with the use of statins, drugs used to lower cholesterol. In some patients, they cause agitation or confusion, which can lead a physician to prescribe an unnecessary antipsychotic. In others they cause insomnia, which can end with a prescription for sleeping pills.

Another example involves nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or diclofenac. These molecules —used for pain, inflammation and fever— can raise blood pressure and lead to an erroneous diagnosis of hypertension and the prescription of a drug to treat it, when it would be preferable to replace the NSAID with another medication.

The Catalan health campaign warns that prescribing cascades not only increase the use of unnecessary drugs but also “multiply the risk of new adverse effects and interactions,” and “overload the health system and the patient with extra doctor visits, diagnostic tests, emergency visits and avoidable hospital admissions.”

The experts consulted by this newspaper agree on certain moments when a prescribing cascade is more likely to begin. One is a visit to an emergency room for an acute episode, explains Daniel Sevilla of the Spanish Society of Hospital Pharmacy (SEFH). “The priority in these cases is resolving a life-threatening problem, which may require a new drug. Because any adverse effects it may cause will take days or weeks to appear, it will be harder to identify the drug as the cause of the symptoms, and the patient may be prescribed another drug to treat them,” he describes.

Care fragmentation

Another factor that facilitates cascades is so-called “care fragmentation,” which occurs when a patient sees multiple specialists who diagnose and treat conditions within their own area of expertise without coordinating with others. This situation gives primary care a key role in identifying and preventing these problems. “Continuity of care is very important. We know the patient’s history and whether they have had similar episodes in the past. So we can more easily see if a recent change in medication might be causing problems,” says Mariam de la Poza, Catalan president of the Spanish Society of General Practitioners and Family Physicians (SEMG).

At the hospital level, services such as internal medicine most often face these cases. “A major obstacle with prescribing cascades is that they can go unnoticed and are very difficult to identify if the physician does not keep this possibility in mind and does not thoroughly review all treatments,” explains Virginia Gracia of the Spanish Society of Internal Medicine (SEMI).

She illustrates this with an example: “A very alarming symptom is sudden weight loss in an older person. It can suggest serious illnesses, even cancer, which sometimes leads to diagnostic tests and new treatments and causes great concern for the patient and their family. I have seen cases where, in the end, everything was due to digestive changes caused by an iron supplement.”

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