What Is Tianeptine and Why Is It in Demand?

— Here’s why this unregulated compound is known as “gas station heroin”

by
Rachael Robertson, Enterprise & Investigative Writer, MedPage Today
February 1, 2024

An uptick in adverse events connected to unregulated tianeptine products — often referred to as “gas station heroin” — along with the voluntary recall of a popular product have brought renewed attention to the atypical tricyclic antidepressant.

Earlier this week, the company that makes a product called Neptune’s Fix issued a voluntary recall of several of its products due to “undeclared tianeptine.” The move follows a warning from FDA last November urging consumers not to purchase or use Neptune’s Fix products or products with tianeptine, given reports of seizures, loss of consciousness, and death.

So what is tianeptine and why is it becoming so popular?

Daniel Lasoff, MD, emergency medicine physician and toxicologist at University of California San Diego Health, told MedPage Today that the compound “has some opioid receptor activity, which is unusual for a tricyclic antidepressant.”

“We’ve had a pretty large migration away from tricyclic antidepressants as a first-line drug,” Lasoff said, noting that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have taken their place.

Some tricyclic antidepressants, such as nortriptyline (Pamelor), imipramine, and amitriptyline are still commonly used, though “those drugs don’t typically have any opioid agonism,” he said.

Tianeptine was developed in the 1960s and is used in some parts of Europe, Asia, and South America to treat depression and pain. Some brand names include Coaxil, Stablon, and Tatinol.

But in order for tianeptine to ever be used clinically here in the U.S., there would need to be solid research and clinical trials, Lasoff said.

“I don’t think it’s a particularly effective drug with a good safety profile compared to what’s already available out there,” he said.

Since tianeptine is not regulated and is easily available in powder, liquid, or capsule form at gas stations and online, its popularity has surged. According to the FDA, there were only 11 total tianeptine exposure cases at poison control centers from 2000 to 2013, but in 2020 alone there were 151 cases.

A recent report from New Jersey’s poison control center published in Morbidity & Mortality Weekly Report highlighted an “uncharacteristic spike” in patients who became critically ill after ingesting contaminated tianeptine products.

Among the 17 patients identified, 14 took products made by Neptune’s Fix, Christopher Counts, MD, of Rutgers New Jersey Medical School, and colleagues reported. Thirteen of the 17 patients were admitted to the ICU and seven required intubation. Patients reported symptoms such as tachycardia, hypotension, seizure, and cardiac arrest.

After testing six bottles of the product, the CDC found “variable composition,” and some were contaminated with emerging synthetic cannabinoids, they reported.

“It’s important for members of the public and healthcare professionals to be aware that readily purchased tianeptine products might be adulterated with synthetic cannabinoid receptor agonists or other drugs and can produce severe adverse effects,” the researchers cautioned.

Lasoff also warned that people who buy and use tianeptine products “tend to develop dependency or addiction” and then doctors “see people develop withdrawal syndromes from them.”

In a 2023 narrative review of tianeptine’s pharmacology and abuse potential published in Pain and Therapy, Amber Edinoff, MD, and co-authors wrote that tianeptine can act as a full agonist at the mu-opioid receptor and “its short half-life can lead to rapid withdrawal, increasing its potential for addiction and misuse.”

Reddit has a “quitting tianeptine” forum with more than 5,200 members. Some people share stories of trying to stop using tianeptine while others post about using tianeptine to lessen dependency on other substances, like kratom.

Lasoff said he’s heard of both situations, and rather than trading one drug for another, “the smart thing to do would be to use some sort of replacement therapy that is already approved and has good research behind it — things like buprenorphine or methadone,” which both have long half-lives. He also urged fellow doctors to talk to their patients about supplements and substances.

Last month, five members of Congress, including emergency physician Rep. Rich McCormick, MD, (R-Ga.) wrote a letter to FDA commissioner Robert Califf, MD, urging the FDA to issue guidance on tianeptine.

Specifically, they wanted the FDA to research the health effects of using and overusing tianeptine and investigate whether it should be a controlled substance.

A few days after the letter, Rep. Jimmy Panetta (D-Calif.) introduced a bill to Congress to “amend the Controlled Substances Act to provide for the scheduling of tianeptine as a schedule III substance, and for other purposes.”