"Off-label" antidepressant use is common, but is it safe?

Doctors often prescribe antidepressants to tackle conditions like migraine headaches for which they aren’t technically approved. Now, researchers say such “off-label” usage mostly occurs without clear scientific evidence backing up the treatments.

A new Canadian study found that almost one-third of antidepressants are prescribed for pain, insomnia, migraine or other unapproved uses.

But just 16 percent of those off-label prescriptions were found to be supported by strong research.

Study lead author Jenna Wong described the findings as “eye-opening” but in line with the findings of prior investigations.

Wong, a doctoral candidate in epidemiology, biostatistics, and occupational health at McGill University in Montreal, said she hopes the findings raise awareness among doctors.

“Some physicians may not be aware that certain off-label antidepressant uses are not evidence-based, especially if the broader community of physicians prescribes antidepressants for these off-label uses so frequently that it seems like the norm,” she said.

Doctors prescribe off-label for other reasons as well.

In cases where the approved medication carries major side effects — such as insomnia drugs for older patients — “physicians may prescribe antidepressants instead of thinking that these drugs are safer,” Wong said.

The new findings stem from an analysis of more than 100,000 antidepressant prescriptions issued in Quebec, Canada, between 2003 and 2015. They were written by 174 Quebec doctors.

According to the study, trazodone was the most common off-label use for antidepressants. It’s often prescribed to help people sleep.

In terms of class of drugs, tricyclic antidepressants like amitriptyline were the most likely to be prescribed off-label. This is a common migraine treatment.

Antidepressants known as selective-serotonin reuptake inhibitors (SSRIs) — including fluoxetine (Prozac) and sertraline (Zoloft) — were less likely to be used off-label. That was also the case for drugs like venlafaxine (Effexor), which is a serotonin-noradrenaline reuptake inhibitor (SNRI), the study found.

The researchers said 44 percent of the alternative drugs lacked any strong research backing up the effectiveness of the intended off-label purpose. Another 40 percent lacked evidence for the medicine at hand, but did have strong evidence supporting use of a similar drug in the same class for the intended off-label usage.

Wong said she expected “trends to be similar” in the United States, although she can’t be sure.

The results were published online Feb. 21 in BMJ.

The author of an accompanying journal editorial, Daniel Morales, pointed out that off-label use “has always happened.”

“Some off-label prescribing has strong evidence, but pharmaceutical companies may not apply for a license for a new indication because it is a complex and expensive process,” said Morales, a fellow in the school of medicine at the University of Dundee in Dundee, Scotland.

The bottom line is that “the strength of evidence for using an antidepressant for a particular patient or condition” is equally important whether the antidepressant is used “on” or “off” label, said Morales.

Dr. David Katz, director of the Yale University Prevention Research Center in New Haven, Conn., cautioned against painting off-label prescribing in a broadly negative light.

The practice “invites concern and caution, but does not necessarily indicate poor choices,” he explained.

“I have prescribed off-label many times myself, and generally it was because my patient needed me to get creative to figure out how to help them when the more obvious choices had failed for various reasons,” Katz said.

He agreed that because the regulatory approval process is so expensive, drug companies often stop after acquiring approval in one area of use.

“But to be clear,” he added, “a product might work just as intended (or) hoped, even if there is no multinational randomized trial in the thousands to prove it,” Katz added.

Wong and her team suggested more research is needed to examine the effectiveness of off-label antidepressant uses.

Also, “when evidence is lacking, we encourage physicians to prescribe conservatively or engage with their patients in a shared decision-making process to decide whether taking an antidepressant is the right choice for them,” Wong added.