Off-label drug use in Quebec common, but risky: study
Recommending drugs to treat health conditions for which they were not tested — or approved — sharply increased patients risk for serious side-effects, a unique Quebec study found.
“Off-label” prescription is common and legal, but the practice is hard to track. Still, an extensive investigation by researchers at McGill University did just that, by looking at 46,021 patients who received 151,305 medications, as documented in Quebec’s electronic health records. Off-label use was reported in 17,847 prescriptions.
Montreal researchers looked at family doctors’ prescriptions dispensed from 2005 through 2009 and identified a total of 3,484 bad drug reactions or “adverse events.”
However, patients were up to five times more likely to have allergic reactions and other side effects that forced them to stop the treatment — when the drugs they got were off-label, and without scientific value. Those who took more off-label drugs had more unwanted reactions.
Nearly 12 per cent of physicians’ prescriptions were off-label and of these, more than 80 per cent have no scientific evidence for non-approved use, the study found.
“Four of five drugs had no strong scientific backing,” said Tewodros Eguale, who led the research team at McGill University.
The most common medications prescribed off-label are those that affect the central nervous system, he said, specifically, antidepressants, antipsychotics and anticonvulsants. Patients reported various unwanted effects — from weight gain, nausea and abdominal pain, to grogginess, dizziness, loss of balance and confusion.
The antidepressant trazodone (Desyrel), when prescribed offlabel to treat insomnia, is linked to hallucinations.
Neurontin, also known by its generic name gabapentin, is approved for use in Canada and the United States to help control epileptic seizures, but is often prescribed for pain, “and there’s no sufficient evidence that it works,” Eguale said.
The study raises concerns about the increasing use of off-label drugs and patient safety. “There are risks for serious consequences,” Eguale said. The malaria drug quinine is also prescribed, though not approved, for nighttime leg cramps and restless leg syndrome, and side effects include bleeding.
Powerful antipsychotic drugs like quetiapine (Seroquel) and risperidone (Risperdal), which are approved for the treatment of schizophrenia and bipolar disorders, are often used off-label for depression and anxiety; these medications are linked with irregular heart beat, Eguale said.
“The effect on heart rhythm, now that’s worrying,” he said. Other studies have linked these medications with a higher risk “for lifethreatening arrhythmia.”
There has been concern for decades that once drugs are approved for market they can be prescribed for conditions for which they were not approved by regulatory bodies, like Health Canada or the U.S. Food and Drug Administration, said study senior author, Robyn Tamblyn, of the Research Institute of the McGill University Health Centre, professor in the departments of medicine, epidemiology and biostatistics at McGill University.
Asked why physicians would recommend drugs off-label without scientific evidence they are safe or efficient, Tamblyn suggested that some doctors are not up to date on the latest scientific literature, or are persuaded by “companies’ marketing for off-label uses, although there are regulations against that.”
Individuals most at risk for unwanted side effects are seniors age 65 and older, who are more likely to have multiple chronic conditions for which they take multiple drugs, Tamblyn said. “The number of drugs you use increase — like a line — as you age.”
“We looked at whether adverse drug events were more likely to occur in seniors, and sure enough they were,” she said. “And the number of drugs is the strongest predictor. There’s the aging metabolism but also the issue that the probability that you’re going to have problem increases with the number of drugs that you are on.”
Provinces are now investing in pharmacists and hospitals doing reviews of medications in older patients who have accumulated therapies over the years, some up to 18 pills a day, she said, “and there is insufficient information about why they got started, what was the condition, are they still taking it regularly or too much of it ...”
The study has limitations, researchers noted, because physicians are known to miss medication-related symptoms, patients may not inform their physicians about all of their symptoms, and patients with multiple illnesses may not attribute unwanted reactions to their medications. However, the study’s numbers show a rate of unwanted side effects that is 40 times higher than Health Canada’s record of drug side effects, she said.
Published Monday online in JAMA Internal Medicine, the study was funded by the Canadian Institutes of Health Research.