It just goes on and on…
February 24, 2021
While the agency investigated, people were harmed, even died after taking the opioidlike substance
All around the country, in late 2017 and early 2018, alarm bells were going off regarding a drug called tianeptine.
In Michigan, lawmakers sought to ban sales of the drug, which has opioidlike effects, after reports that users became addicted. In New York, researchers found that it could lead to abuse and overdose. In Texas, a couple alleged that their son had died as a result of taking the drug.
Now, emails obtained by Consumer Reports reveal that the Food and Drug Administration at the time was also looking into the dangers of tianeptine, which is used as a dietary supplement ingredient despite being illegal. But the agency—which regulates drugs and supplements in the U.S.—waited at least nine months to alert the public about the risks.
A recent investigation by CR found significant shortcomings with the agency’s enforcement efforts around tianeptine. The new emails, obtained through the Freedom of Information Act, underscore concerns about the FDA’s ability to effectively police the $46 billion dietary supplement industry.
“When there are blatant examples of illicit drugs being sold as supplements, particularly drugs that are known to be harmful, we need to have an agency that’s proactive,” says Pieter Cohen, MD, a Harvard Medical School associate professor who studies dietary supplements.
Tianeptine appears to have arrived in the U.S. in the mid-2010s, when opioid-crisis crackdowns on fentanyl and oxycodone drove people to seek cheaper and easier-to-come-by alternatives.
At least four people have died using it, CR’s report found. It remains available for sale online to this day.
The FDA denies dragging its feet, citing instead its intensive review process. The agency must analyze the ingredient, do a market survey, and collect documentation of harm, says Courtney Rhodes, an FDA spokesperson. “Those things take time, especially when done in the context of limited resources and competing priorities,” she says.
But health experts, consumer advocates, and supplement industry groups say the FDA had slam-dunk evidence of harm and illegality and should have brought enforcement action against tianeptine manufacturers much faster.
“It’s not a resource issue,” says Daniel Fabricant, PhD, president of the Natural Products Association, a supplements industry group, and a former director of the FDA’s supplements division. “These are easy cases.”
Chuck Bell, programs director in CR’s advocacy division, says the nation’s dietary supplement safety system should have “zero tolerance for illegal and unregistered prescription drugs in supplements.”
“These products should have been pulled off the market in 24 or 48 hours—not after months or years,” Bell says. “But Congress also needs to strengthen federal supplement safety laws so that zero tolerance is hardwired into the oversight and enforcement system.”
‘People Got Hooked’
The emails obtained by CR show that when the FDA began investigating tianeptine in early 2018, it appeared to be operating with little sense of urgency and failed to develop a full view of the problem.
The earliest communication in the records CR obtained was from Bob Durkin, then-deputy director of the FDA’s supplements office, who on Feb. 22 wrote an email to colleagues with the subject “TIANAA/tianeptine.” (Tianaa is the brand name of a popular tianeptine supplement.)
“I’m coming to this late,” Durkin wrote by way of apology.
None of the FDA emails mention what was happening in Michigan at the time. There, lawmakers were working to pass legislation to ban the sale of tianeptine after a flurry of adverse event reports linked to the drug alarmed health experts and law enforcement. Several users interviewed by Michigan state police described the effects of tianeptine as being “worse than heroin,” a spokesperson told CR last month.
Michigan lawmakers received written testimony from Alyssa Wood, a local resident and former heroin user who described her addiction to tianeptine.
“The withdrawal that I experienced from heroin was [overshadowed] by the withdrawal from this poison,” she wrote in February 2018.
Several studies have linked tianeptine to addiction. But emails suggest Durkin’s colleagues unearthed none of them.
“This product is inadequately regulated in the United States and poses a risk to public health.”
—Conclusion from a May 2018 article on tianeptine in the journal Clinical Toxicology
Even new reports of harm seem to have escaped the FDA’s notice. A May 2018 article in the journal Clinical Toxicology examined tianeptine-related poison control calls in New York. The researchers noted several exposure calls citing adverse effects and advised that the drug posed “risk for abuse, overdose, and physical dependence.”
“This product is inadequately regulated in the United States and poses a risk to public health,” the researchers wrote.
Nor did the FDA apparently heed warnings captured by its own adverse-event database, where several alarming incidents involving tianeptine use were reported by consumers. Tianeptine in high doses, one consumer wrote in 2016, provides euphoric effects similar to those of opioids, while tolerance “skyrockets with each use.”
“People like myself got hooked on it,” the consumer wrote, adding that anecdotal evidence of risks was readily available on the internet, including on social media site Reddit. The consumer also provided names of websites where tianeptine was available for purchase. Narrative summary from report submitted to the FDA about an incident linked to tianeptine.
Durkin, now a lawyer in private practice, says it’s difficult to remember the specifics of what he and FDA colleagues did or did not do in 2018. But, he says, federal law requires the agency to follow an “extensive” process before taking action on a supplement suspected of causing harm.
“FDA also has its limitations,” he says. “There is often not enough information for FDA to establish causation, and it is difficult for the agency to independently develop a basis for how a product is harming people.”
Fabricant, the former FDA supplements office director, says he doesn’t understand why the FDA review of tianeptine took so long. One aspect the agency considers is whether an ingredient is eligible to be used in dietary supplements; tianeptine, which is not a botanical, is not. “Nobody is saying it’s anything other than a drug,” he says.
In the summer of 2018, the FDA received another serious report detailing the death of a 24-year-old man who suffered a fatal brain injury after taking tianeptine. A month later, the Centers for Disease Control and Prevention sounded alarm bells. The agency found a sharp uptick beginning a few years earlier in the number of calls to poison control centers citing tianeptine.
“The associated outcomes and health effects associated with tianeptine use suggest a possible emerging public health risk and underscore the need for public outreach to increase awareness,” the CDC wrote in a report.
‘We Won’t Stand By’
The emails obtained by CR indicate that within weeks of the CDC report, the FDA drafted warning letters to send to tianeptine manufacturers. But the agency did not issue an alert to the public or put tianeptine sellers on notice about selling their products until November.
In a statement at the time, then-FDA commissioner Scott Gottlieb, MD, pointed out that companies were marketing tianeptine to opioid addicts who may be seeking alternative drugs.
“They’re also selling products with known safety issues,” Gottlieb said. “We won’t stand by and allow this to happen.”
The effect of the agency’s alerts appear to have been limited. Tianeptine-related poison control calls jumped to a record high in 2020, CR reported last month. One vendor warned by the agency in 2018 continues to sell tianeptine supplements, according to a review of the company’s website this week.
The Center for Science in the Public Interest, an advocacy group based in Washington, D.C., and other consumer advocates urged the FDA last August to clamp down on tianeptine sales (PDF), but as of last month, an agency spokesperson said it was still reviewing the request.
Laura MacCleery, policy director at the CSPI, says regulatory agencies move at a “glacial pace” and that it’s a particular problem with the FDA not acting expeditiously on public health threats.
Cohen, the Harvard professor, agrees that the FDA’s slow response to tianeptine is par for the course.
“You need an agency that’s going to get the job done in a timely fashion,” he says.