Tianeptine Misuse Raises Concerns Across US, but is Stigmatizing the Drug Helpful?

Gas station convenience stores are a one-stop shop for many busy consumers looking to grab a quick coffee or snack while on the go. The inventory of these stores is constantly expanding with new flavors of energy drinks and countless other novelties to bring in customers. However, over the past several years, a more harmful type of product has begun to proliferate on their shelves: Synthetic drugs seeking to mimic the effects of controlled substances.

Tianeptine, often referred to as “gas station heroin,” has led to serious adverse effects / Heorshe - stock.adobe.com

Tianeptine, the most recent of these so-called “gas station drugs,” has caused both lawmakers and public health officials across the country to sound the alarm. In some states, such as Michigan, Alabama, Georgia, Ohio, and Florida, sales of the drug have either been regulated or banned altogether. Representatives August Pfluger (R-TX) and Jimmy Panetta (D-CA) have also moved to restrict tianeptine, introducing bipartisan legislation that would make it a Schedule III drug under the Controlled Substances Act.¹

In January 2023, the FDA issued a warning to consumers advising them not to purchase any product that contains tianeptine.² In its announcement, the agency said they had received several adverse event reports related to a popular tianeptine product called Neptune’s Fix. Symptoms noted in the letter included seizures and loss of consciousness that led to hospitalization. But the list of potentially harmful effects from high doses of tianeptine is much longer: Users can also experience rapid heartbeat, high blood pressure, vomiting, slowed or stopped breathing, and even death.³

Christopher J. Counts, MD, a toxicology fellow at the New Jersey Poison Control Center at Rutgers New Jersey Medical School, said that although it’s hard to get concrete numbers, calls to the poison control center involving tianeptine have been increasing year to year. In a CDC Morbidity and Mortality Weekly Report published in February 2024, Counts and his colleagues said there were 20 cases of “severe clinical effects” associated with tianeptine use reported to the poison control center between June and November of 2023. That’s compared to just 2 or less annual calls total in previous years.⁴

“Some of the earlier publications in the academic literature about [tianeptine] were [published] around 2016 or 2017 from a couple of different poison centers,” Counts said. “[W]e've definitely had some signals for a number of years about it. But I think the volume at which we're hearing about adverse effects from [tianeptine are] definitely picking up rapidly, especially over the past year or 2.”

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Tianeptine is an atypical tricyclic antidepressant that was developed in the 1960s by the French Society of Medical Research.⁵ It is unique from other antidepressants at both the molecular and mechanistic level. It has been shown to interact with the µ- and δ-opioid receptors, which means it can produce similar euphoric effects as opioid agonists such as heroin and morphine. In some European, Asian and Latin American countries, tianeptine is approved to treat major depressive disorder and anxiety.⁶ In the US, tianeptine is not approved by the FDA for any medical purpose, but that hasn’t stopped people from getting their hands on it.

Aegis Sciences Corporation, which provides laboratory testing services to health care providers, pharmaceutical companies and other organizations for substance abuse, drug-drug interactions and medication compliance, has detected tianeptine in drug tests in approximately 80% of US states, said Andrew Holt, PharmD, a clinical pharmacist with the company. According to Holt, the most concerning aspect of people buying unregulated tianeptine is that most of the companies selling it do not list everything that’s in the product on the label.

“The question, as far as labeling goes, is: What’s the quantity on the label?” Holt said. “What's in the actual product? That will always be a question. Could there be other substances in there as well? There's some formulations that may have other products in them… That's the other unknown. It's a supplement, so it's not regulated. It’s ‘buyer beware.’”

The tianeptine-associated adverse events that have occurred in the US are likely due to adulteration and the high doses the drug is sold in. In countries where it is used as a therapeutic, doses generally range anywhere between 12.5 to 50 milligrams, Holt explained. But the companies marketing it as a dietary supplement in the US sell it in doses upwards of 3000 milligrams. It’s at these significantly higher doses where it’s believed that tianeptine begins to interact with opioid receptors, producing the high that most consumers are purchasing it for.

The availability of tianeptine in gas stations, convenience stores, and other retail shops gives the false impression that it is a safe product to use. However, given the lack of regulation, potential for adulteration, and high doses in which it’s sold, that is far from the truth. In the form it is sold in the US, there is a high potential for chronic users to develop tolerance and dependence, leaving many addicted and not sure who to turn to for help.

This is an area where pharmacists can play a role, according to Savannah Roberts Clary, PharmD, BCPS, CPGx, who also works as a clinical pharmacist at Aegis. But getting educated on tianeptine first is crucial, she said. Although tianeptine may not be something that is on most independent pharmacists radars—at least not yet—becoming familiar with the drug will allow pharmacists to help any patients who may have questions about it. Clary added that there are a number of places where pharmacists can go for validated information on tianeptine, including resources from the FDA and Drug Enforcement Administration.

While many are justifiably concerned about consumers potentially being harmed from using unregulated tianeptine, there are others who fear the negative attention the drug is getting may hurt its future prospects of medicinal use in the US. Jonathan A. Javitch, MD, PhD, professor of experimental therapeutics in psychiatry, and molecular pharmacology and therapeutics at Columbia University, who is conducting research on the therapeutic benefits of tianeptine, said there needs to be a better way to warn people of the dangers of tianeptine misuse without completely stigmatizing the drug itself.

“[Tianeptine is] not controlled, so you don’t know what the dose is,” Javitch said. “You don’t know what it’s cut with. I think that’s a bad idea. But what I’m finding unfortunate is that [tianeptine availability and use] is producing outrage.…People are describing reactions, but it's taken out of the context of its proper use in research and medicine. Just because something is being misused in certain ways, doesn't mean there's not something potentially revolutionary about its use in a proper, controlled way.”

A quick Google search of tianeptine will produce plenty of legitimate medical information, but it will also yield news stories with sensationalist headlines meant to pull in readers. The term “gas station heroin” is used frequently; other stories include phrases like “deadly chemical compound” and “stuff that will kill you.” Using this type of language may seem understandable from a public health perspective: Media companies are just trying to warn their readers about a potentially harmful substance that they could easily pick up from the closest gas station. But these stories may also be ruining any chance investigators had of bringing a medicine that may help people to market.

Decades of research have proven tianeptine to be an effective medication. It has been shown to be at least as effective as many antidepressants and can be more effective than some anxiety medications.⁷ Other studies have shown tianeptine can help manage chronic pain, relieve symptoms of irritable bowel syndrome, and improve cognition in patients with Alzheimer's disease.^8,9,10 Although none of these benefits take away from the fact that real harm can be caused by misusing tianeptine, a more balanced approach to how the drug is portrayed could warn the public about its potential dangers while not demonizing it.

“Use of things in an uncontrolled way is not a good idea,” Javitch said. “This compound seems to have really interesting properties and it’s being studied in the lab. It’s being studied in an FDA approved research study…We’re trying to understand who this medication will work for. These are diseases that are life crippling. And if [tianeptine], used in a proper way, can really make a difference, we don’t want to stigmatize it and throw the baby out with the bathwater.”

Make sure to check out part 2 from this series on tianeptine.

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References

1. PFLUGER INTRODUCES BIPARTISAN LEGISLATION TO CRACK DOWN ON 'GAS STATION HEROIN'. News Release. Congressman August Pfluger. January 25, 2024. Accessed May 21, 2024. https://pfluger.house.gov/news/documentsingle.aspx?DocumentID=984

2. FDA warns consumers not to purchase or use Neptune’s Fix or any tianeptine product due to serious risks. News Release. FDA. February 15, 2024. Accessed May 21, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-neptunes-fix-or-any-tianeptine-product-due-serious-risks

3. Tianeptine Products Linked to Serious Harm, Overdoses, Death. Report. FDA. February 10, 2022. Accessed May 21, 2024. https://www.fda.gov/consumers/consumer-updates/tianeptine-products-linked-serious-harm-overdoses-death

4. Counts CJ, Spadaro AV, Cerbini TA, et al. Notes from the Field: Cluster of Severe Illness from Neptune’s Fix Tianeptine Linked to Synthetic Cannabinoids — New Jersey, June–November 2023. MMWR Morb Mortal Wkly Rep 2024;73:89–90. DOI: http://dx.doi.org/10.15585/mmwr.mm7304a5

5. National Center for Biotechnology Information. PubChem Compound Summary for CID 68870, Tianeptine. https://pubchem.ncbi.nlm.nih.gov/compound/Tianeptine. Accessed May 21, 2024.

6. Edinoff AN, Sall S, Beckman SP, et al. Tianeptine, an Antidepressant with Opioid Agonist Effects: Pharmacology and Abuse Potential, a Narrative Review. Pain Ther. 2023;12(5):1121-1134. doi:10.1007/s40122-023-00539-5

7. Wagstaff AJ, Ormrod D, Spencer CM. Tianeptine: a review of its use in depressive disorders. CNS Drugs. 2001;15(3):231-259. doi:10.2165/00023210-200115030-00006

8. Serafini, R.A., Estill, M., Pekarskaya, E.A. et al. Tianeptine promotes lasting antiallodynic effects in a mouse model of neuropathic pain. Neuropsychopharmacol. 48, 1680–1689 (2023). https://doi.org/10.1038/s41386-023-01645-w

9. Sohn W, Lee OY, Kwon JG, et al. Tianeptine vs amitriptyline for the treatment of irritable bowel syndrome with diarrhea: a multicenter, open-label, non-inferiority, randomized controlled study. Neurogastroenterol Motil. 2012;24(9):860-e398. doi:10.1111/j.1365-2982.2012.01945.x

10. García-Alberca JM, Gris E, de la Guía P, Mendoza S. Effects of Tianeptine Treatment on Depression and Cognitive Function in Patients with Alzheimer's Disease: A 12-Month Retrospective Observational Study. J Alzheimers Dis. 2022;88(2):707-720. doi:10.3233/JAD-215630