Medical journals and reports to the FDA suggest that bad effects may occur when tianeptine is taken at doses higher than those prescribed in the countries where the drug has been approved. These reports describe U.S. consumers taking daily doses between 1.3 and 250 times the daily tianeptine dose typically recommended in products approved in other countries. Tianeptine is a non-prescription antidepressant that has become a popular method of getting high in the US in the past decade. It’s even been found in powder form in counterfeit pills of hydrocodone and oxycodone. Some products market dietary supplements containing tianeptine under the brand names Tianaa, Tianna Green, Tianna Red, Tianna White, and ZaZa.
The authors concluded that LC-TOF-MS is effective in identifying tianeptine in a sample and LC-MS-MS in accurately quantifying tianeptine levels in the serum 9. While many use tianeptine to treat their ailments and assume they are safe because of their availability. However, the FDA said tianeptine is a prime example of availability not indicating effectiveness or safety. The work reported in this manuscript was supported by a VA Merit Review Award and a grant from I.R.I. Servier. We thank Adam Campbell for his technical assistance in the surgical and behavioral components of this work.
What are the implications for public health practice?
All data presented in this manuscript can be found in studies indexed in PubMed. No human subjects/data were involved in the construction of this manuscript outside of the original studies in this review. Amber N. Edinoff, Scott P. Beckman, Andrew D. Koepnick, and Logan Gold was responsible for writing the original draft of the manuscript.
Information for health care providers
This manuscript is a narrative review, highlighting the dangers of tianeptine and other “gas station drugs” and underscoring the urgent need to regulate these substances. Tianeptine is a medication approved in some non-US countries for anxiety and depression. It has not been approved by the FDA, but there has been an increase in people using tianeptine in the US.
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Tianeptine is still available at gas stations and convenience stores in 41 other states and is purchasable online. It’s up to individuals to know the dangers and avoid purchasing any related products. MDMB-4en-PINACA belongs to a new generation of synthetic cannabinoids that are characterized by the presence of an alkene tail and were first identified in drug material from European prisons in 2017 19, 20. In-vitro analysis of CB1 receptor activation showed MDMB-4en-PINACA to be the most potent of this group of compounds 20. Whole blood from two additional patients (different from those who provided product samples) was collected and sent to NMS Labs (Horsham, PA) by the providers caring for the patients. Specimens were tested for tianeptine and 14 synthetic cannabinoids and quantified for tianeptine using liquid chromatography tandem quadrupole mass spectrometry (LC-QQQ-MS).
What are the risks of using tianeptine?
Despite that, some companies are illegally marketing and selling products containing tianeptine to consumers. Tianeptine is an atypical tricyclic antidepressant that is approved in some European, Asian, and Latin American countries primarily for the treatment of MDD. Tianeptine was developed to help increase serotonin uptake in the brain; it can also act as a full agonist at the mu-opioid receptor.
- No funding or sponsorship was received for this study or publication of this article.
- Moreover, some findings are inconsistent with the monoamine hypothesis of depression, thereby suggesting that the neurochemical basis of the disorder is more complicated than previously considered.
- In contrast to tianeptine, administration of the SSRI fluoxetine increased baseline and stress-induced levels of glutamate in the BLA and CeA 159.
- The drug increases opioid activity in the brain, a similar mechanism of action seen in heroin.
- In partial agreement, an analysis by Bailey et al. that reviewed all accessible tianeptine clinical trial data reported that tianeptine is effective as an antidepressant, allowing for improved functionality compared to standard first-line antidepressant medications.
A similar trend has been seen nationwide with 151 tianeptine poisoning cases in 2020. There are also reports of at least five fatal overdoses since the drug started being sold in the US. Historically, there has been a delayed recognition of fast-growing trends, such as opioid abuse and vaping addiction in youth. Let’s be proactive in understanding and addressing the use of tianeptine products, which are available even to our nation’s youth.
Depression is a common mental disorder for which effective pharmacological treatments are lacking. Investigators have utilized animal models of depression to develop a better understanding of the neurobiological basis of this disorder, which could ultimately produce improved treatment options for the patient. We have reviewed the findings of preclinical research demonstrating that tianeptine prevents the deleterious effects of stress on physiology and behavior. Tianeptine prevents chronic stress-induced morphological changes in the hippocampus and amygdala and blocks the effects of acute stress on synaptic plasticity in the hippocampus and prefrontal cortex. We have also reviewed findings demonstrating that tianeptine has memory-protective properties, in which tianeptine-treated rats exhibited intact hippocampus-dependent memory despite their being exposed to powerful fear-provoking stressors. Tianeptine’s prevention of the adverse effects of stress on brain and behavior is likely to contribute to its effectiveness as a treatment for people suffering from major depressive disorder.
Amber N. Edinoff, Saveen Sall, Eric D. Jackson, Danielle M. Wagner, Elyse M. Cornett. Kevin S. Murnane, Adam M. Kaye, and Alan D. Kaye was responsible for all revisions of the manuscript. No funding or sponsorship was received for this study or publication of this article.
- Until recently, Alabama had the highest rate of tianeptine-related calls in the southern U.S., which increased more than 1,400% between 2018 to 2021.
- It is important for members of the public and health care 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.
- Department of Health and Human Services.Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S.
- Still, under-the-radar firms sell tianeptine in various formulas, often with brand names like Zaza, Tianaa, Pegasus and TD Red.
- Each call to NJPIES is entered into Toxicall® by a Certified Specialist in Poison Information, producing an electronic record that captures demographic and clinical information, as well as free text descriptions of the exposure history.
Why have there been recalls of tianeptine products, like Neptune’s Fix?
The latest information on products and trends in the convenience-store and foodservice industries. “Nevertheless, tianeptine is being marketed as a ‘research chemical,’ a ‘nootropic’ cognitive enhancer, or a dietary supplement,” the letter said. This section collects any data citations, data availability statements, or supplementary materials included in this article. In a case report by Dempsey et al., LC-MS-MS was also used to detect tianeptine, with a mobile phase consisting of water and 20 mM ammonium formate and methanol and 20 mM ammonium formate. This highlights the possibility of using several methods to identify tianeptine in a given sample 26.
Poisoned?
We also have issued import alerts to help detain tianeptine shipments at our borders. The clinical effects of tianeptine abuse and withdrawal can mimic opioid toxicity and withdrawal, according to the Centers for Disease Control and Prevention. Recent research suggests that increasing the levels of monoamines provides only an indirect contribution to antidepressant actions 186. Moreover, some findings are inconsistent with the monoamine hypothesis of depression, thereby suggesting that the neurochemical basis of the disorder is more complicated than previously considered. For instance, traditional antidepressants ameliorate depressive symptoms only in a subset of patients, despite their low levels of monoamines 12, and are largely ineffective for people with severe forms of depression 113,137.
Previously, she wrote for USA Today, where she was selected to help launch the newspaper’s wellness vertical. One explanation for the rise in calls is simply that more Americans are using the products. “It’s kind of this grey area of consumer products, or supplements, where the contents are not regulated or tested the way they would be with a medication,” said Dr. Diane Calello of the New Jersey Poison Information and Education System. Still, under-the-radar firms sell tianeptine in various formulas, often with brand names like Zaza, Tianaa, Pegasus and TD Red.
The investigation was approved by the Rutgers University Institutional Review Board with a waiver of informed consent for research that involves minimal risk. NJPIES is the sole poison center for the state of New Jersey, serving a population of approximately 9 million. Each call to NJPIES is entered into Toxicall® by a Certified Specialist in Poison Information, producing an electronic record that captures demographic and clinical information, as well as free text descriptions of the exposure tianeptine products linked to serious harm, overdoses, death history. This information is coded to produce an entry that can be retrieved when the database is queried based on the exposure of interest or other relevant variables. All cases involving tianeptine exposure reported to NJPIES from June 2023– February 2024 were included. Individual records were reviewed for exposure history, demographic and clinical data.