FDA Needs to Quickly Ban the Illegal Opioid-Like Substance Tianeptine

In recent years, tianeptine — an addictive synthetic chemical compound that has led to abuse, physical dependence (needing to use increasingly higher doses) and withdrawal adverse reactions similar to those of opioids[1] — has emerged as a growing public health threat in the U.S. and internationally.[2],[3]

It has been marketed as dietary supplements in the U.S. under “street” names such as Tianaa and ZaZa[4] to induce euphoria (feeling high); produce opioid-like effects; and treat anxiety, pain and opioid-use disorder, among other unapproved uses.[5]

The unsafe nature of supplements containing tianeptine makes these products “adulterated” under the Federal Food, Drug, and Cosmetic Act, and therefore unlawful for sale in the U.S.

Tianeptine actually is a drug. It has not been approved for any use by the Food and Drug Administration (FDA).[6] However, it has been approved in small doses to treat depression in some Asian, European and Latin American countries under various brand names such as COAXIL and STABLON.

According to Prescrire International, a French independent drug review newsletter, tianeptine has no advantage over approved antidepressants and its risks of abuse and dependence are too high to justify use of the drug.[7]

Because of its abuse potential, the country of Georgia withdrew tianeptine from the market in 2010 and health authorities in other countries (including Armenia, Turkey and Russia) have classified it as a controlled substance.[8]

So far, Alabama and Michigan have passed legislation classifying tianeptine as a Schedule II controlled substance, effectively banning over-the-counter sales of the drug in these two states.[9] Unfortunately, tianeptine continues to be sold unlawfully online — often in high doses — throughout the rest of the country.

Federal study sounds alarm about tianeptine’s risks

According to an August 2018 study by the Centers for Disease Control and Prevention (CDC) that analyzed data from national poison control centers, calls related to tianeptine exposure increased dramatically from a total of only 11 during the 14-year period from 2000 to 2013 to 207 during the four-year period from 2014 to 2017.[10] Most of these calls involved individuals who had consumed tianeptine by mouth, but nearly 10% of the individuals had injected or inhaled it. More than one-half of the reported exposures occurred among users between the ages of 21 and 40, and 12% occurred in younger individuals.

The study showed that for 114 calls — more than half of all 218 calls — there was no reported use of any addictive substances other than tianeptine. Of those, 48% reported neurologic adverse reactions (including agitation, confusion, drowsiness or coma) and 33% reported cardiovascular adverse reactions (including rapid heartbeat and high blood pressure) associated with tianeptine use. Additionally, 11% of these 114 calls reported gastrointestinal adverse reactions (including diarrhea, nausea and vomiting) and 7% reported respiratory adverse reactions (including difficulty breathing or respiratory depression) associated with tianeptine use.

Of 105 exposure calls due to tianeptine toxicity for which the level of medical care was reported, 44% involved patients who were treated and released from an emergency department and 24% involved others who were admitted to a critical care unit.

Of 29 calls with withdrawal reactions (due to sudden tianeptine discontinuation or significant dose reduction), tianeptine was the sole substance implicated in these reactions in 21 cases. The most commonly reported signs and symptoms of tianeptine withdrawal in these 21 calls were agitation, high blood pressure, rapid heartbeat, diarrhea, nausea, vomiting, tremor and sweating.

No deaths were reported in the CDC study. However, other studies reported tianeptine-related fatalities both in the U.S.[11] and internationally.[12]

Deficient and belated FDA action

On Nov. 7, 2018, approximately three months after the publication of the CDC study, the FDA issued warning letters against two online U.S. companies that marketed tianeptine-containing products as dietary supplements.[13],[14]

In these letters, the FDA rebuked the companies for making unfounded therapeutic claims about their tianeptine products even though the substance has not been approved as a drug by the agency. The FDA also noted that these products were misbranded because they did not include adequate directions for their intended use.

Additionally, the agency explained that even if these companies had not made unapproved drug claims about their tianeptine products, these products would not qualify for sale as dietary supplements in the U.S. because, as explained in the introduction of this article, their unsafe nature makes them adulterated under federal law.

In a related Nov. 20, 2018, news release, the agency noted that it had issued the two warning letters following its receipt of serious adverse-event reports associated with tianeptine-containing products.[15] The FDA promised that it would have “more to say… very soon” about its “new policy on how [it] intend[s] to more vigorously fulfill [its] obligations to protect consumers from dangerous products and unlawful claims.”

Although both online companies warned by the FDA appear to have suspended the sale of tianeptine products, many other companies continue to sell such products.

This prompted the Center for Science in the Public Interest, a nonprofit organization that advocates for safer and healthier foods, to send a related letter to the FDA in August 2020.[16] The letter urged the agency to work with other federal, state and local officials to crack down on all companies that are involved in the tianeptine market and take appropriate action to remove these dangerous products from the market.

As of press time, the FDA has not issued new updates about its planned actions regarding tianeptine sale in the U.S.

The prolonged delay in FDA action is unacceptable given the danger posed by these products and the agency’s long-standing legal authority to remove them from the market.

What You Can Do

Stay clear of tianeptine and all other illegal drugs and substances. If you are struggling with anxiety, depression, opioid use disorder or any other condition, do not delay seeking medical attention because doing so can help you heal faster and reduces your risk of adverse effects.

Report all serious adverse events related to tianeptine and other drugs or supplements to the FDA’s MedWatch adverse event reporting program by visiting www.fda.gov/MedWatch or by calling 800-FDA-1088.
 

References

[1] Kisa C, Bulbul DO, Aydemir C, Goka E. Is it possible to be dependent to tianeptine, an antidepressant? A case report. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(3):776-778.

[2] Rushton W, Whitworth B, Brown J, et al. Characteristics of tianeptine effects reported to a poison control center: a growing threat to public health. Clin Toxicol. 2021;59(2):152-157.

[3] Lauhan R, Hsu A, Alam A, Beizai K. Tianeptine abuse and dependence: Case report and literature review. Psychosomatics. 2018;59(6):547-553.

[4] Rushton W, Whitworth B, Brown J, et al. Characteristics of tianeptine effects reported to a poison control center: a growing threat to public health. Clin Toxicol. 2021;59(2):152-157.

[5] Food and Drug Administration. FDA news release. FDA warns marketers of products labeled as dietary supplements that contain tianeptine for making unproven claims to treat serious conditions, including opioid use disorder. November 20, 2018. https://www.fda.gov/news-events/press-announcements/fda-warns-marketers-products-labeled-dietary-supplements-contain-tianeptine-making-unproven-claims. Accessed May 3, 2021.

[6] Food and Drug Administration. Tianeptine in dietary supplements. November 20, 2018. https://www.fda.gov/food/dietary-supplement-products-ingredients/tianeptine-dietary-supplements. Accessed May 3, 2021.

[7] Tianeptine: more cases of dependence. Prescrire Int. 2012;21(127):130.

[8] Durmus N, Ozbilen G, Kasap Y, et al. Risk management in tianeptine abuse in Turkey: A national experience. Bull Clin Psychopharmacol. 2013;23(2):149-154.

[9] Taylor D, Rankin M. Ban of over-the-counter drug tianeptine goes into effect across Alabama. Mar 22, 2021. https://www.cbs42.com/news/local/ban-of-over-the-counter-drug-tianeptine-goes-into-effect-across-alabama/. Accessed May 3, 2021.

[10] El Zahran T, Schier J, Glidden E, et al. Characteristics of tianeptine exposures reported to the National Poison Data System - United States, 2000-2017. MMWR Morb Mortal Wkly Rep. 2018;67(30):815-818.

[11] Bakota EL, Samms WC, Gray TR, et al. Case reports of fatalities involving tianeptine in the United States. J Anal Toxicol. 2018;42(7):503-509.

[12] Durmus N, Ozbilen G, Kasap Y, et al. Risk management in tianeptine abuse in Turkey: A national experience. Bull Clin Psychopharmacol. 2013;23(2):149-154.

[13] Food and Drug Administration. Warning letter to Jack B Goods Outlet Store. November 7, 2018. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/jack-b-goods-outlet-store-566674-11072018. Accessed May 3, 2021.

[14] Food and Drug Administration. Warning letter to MA Labs LLC. November 7, 2018. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/ma-labs-llc-566831-11072018. Accessed May 3, 2021.

[15] Food and Drug Administration. FDA news release. FDA warns marketers of products labeled as dietary supplements that contain tianeptine for making unproven claims to treat serious conditions, including opioid use disorder. November 20, 2018. https://www.fda.gov/news-events/press-announcements/fda-warns-marketers-products-labeled-dietary-supplements-contain-tianeptine-making-unproven-claims. Accessed May 3, 2021.

[16] Center for Science in the Public Interest. Letter to FDA re: Sales of unapproved drug tianeptine. August 25, 2020. https://www.cspinet.org/sites/default/files/attachment/Tianeptine_Letter_FDA_0.pdf. Accessed May 3, 2021.