Doctors like the ability to prescribe medications "off-label." That's when a doctor gives you, say, an anti-epilepsy drug to treat your tinnitus. It's not necessarily approved by the government for that particular use, but it's legal, and as long as it works, you're happy.
But what if they don't really work? When researchers examined 106,850 antidepressant prescriptions over a 12-year-period, they determined that 44 percent of those off-label prescriptions were for uses that have not been extensively studied in the drug itself or other drugs in that class. Only 16 percent of off-label prescriptions were backed up by solid science, although in another 40 percent of prescriptions, a closely related drug in the same class of antidepressants did have research backing for that use.
"The regulatory status isn't that important, what's more important is whether or not it's backed by scientific evidence," says study author Jenna Wong, a PhD candidate studying epidemiology at McGill University in Canada.
Since the 1980s, antidepressant use has quintupled in the United States, according to the Centers for Disease Control and Prevention. A previous study by Wong had found that 29 percent of antidepressant prescriptions were off-label.
It's generally tough to track off-label prescriptions, because doctors may not even note on their charts exactly what they're prescribing a medication for, and pharmacies generally don't ask. So study co-author Robyn Tamblyn created an e-prescription system called "Medical Office of the XXI Century" or MOXXI that requires doctors to mark what ailment they're prescribing a medication for via a pull-down menu and open text box. "There's always a lot of pushback from physicians when other systems have them do that," Wong says. MOXXI was designed with enough other benefits to doctors, however, that it's been adopted by practitioners in and around Quebec City and Montreal.
Aside from adding to the mystery of whether or not the medication really does help, off-label use without scientific support comes with a 54 percent greater risk of harmful side effects, according to a 2015 study in JAMA Internal Medicine. When off-label medications are backed by evidence, however, they carry the roughly same risk as on-label uses, the study found.
As the Food and Drug Administration states on its website, determining that a drug is safe doesn't mean it's risk-free. In fact, "it means the FDA has determined the benefits of using the drug for a particular use outweigh the potential risks," they state. Generally, that means testing the drug extensively, but focusing on the patients who are most likely to use it and get some benefit. "If you prescribe this drug to another patient population, you don't know how they're going to respond to it given their whole profile and medication history," Wong says.
Nevertheless, doctors turn to off-label uses for a number of reasons. It goes like this: Depression often shows up along with other chronic conditions, and doctors who work together in a hospital or clinic might notice anecdotally that patients who were being treated for depression also saw some relief for their pain or insomnia. At the same time, drugs for those conditions might be higher risk for one type of patient, or they might conflict with other medications they're taking. So doctors try the relatively safer off-label antidepressants instead.
There's other factors in play as well. In some cases the Byzantine rules of a patient's insurance might make an on-label drug cost prohibitive, so doctors prescribe a similar but cheaper med instead. And pharmaceutical companies may even market an off-label use for a drug, although the practice is forbidden under US law. Doctors could also read a preliminary study about a novel use for a medication and want to try it in their practice. "There's so much range in quality of studies, some of them have few patients in them or are done poorly," Wong says. "They don't have the time to do a good systematic review and look at all the evidence."
She suggests that closer integration between research databases and e-prescription systems could alert doctors about the various levels of evidence for off-label uses, helping them make better-informed decisions. Wong would also like to find out the true economic cost of off-label drugs. "If the drugs aren't effective, how much have we spent for that?" she asks.
In the meantime, it's always smart to press your doctor a little bit about why they're prescribing a medication to you, and how it works. If you don't like the answer, see if they can suggest a drug that's more established.