(47) ''Gas Station Heroin'': Tianeptine, a Unique Tricyclic Antidepressant

Background & Introduction: Tianeptine is an atypical tricyclic antidepressant that has been approved for the treatment of major depressive disorder in countries other than the USA [2]. The medication has shown some potential for the treatment of anxiety, and irritable bowel syndrome but is not currently approved by the United States Federal drug authority(FDA) for any use [1]. Tianeptine has gained popularity as a “gas station drug,” being sold by various gas stations, bodegas, corner stores, smoke shops, and on the internet. The drug is sold under the brands “ZaZa'' and “Tianna Red,” being advertised as a nootropic drug, a supplement that can help boost mood and cognition [2]. “Gas station drugs” can be produced commercially or surreptitiously by laboratories with the goal of imitating other substances such as opioids, cocaine, and marijuana [1]. Tianeptine has a wide array of mechanisms of action, including serotonergic modulation, glutamatergic effects, and opioid agonism [1]. It is a full mu-opioid receptor agonist, as well as a weak delta opioid agonist, resulting in a high potential for abuse due to the subsequent euphoric state. Because of the opioid receptor agonism, Tianeptine has gained the alternative name of “gas station heroin” and has substantial abuse potential [1].

Case Description: Case 1:
A 32-year-old Caucasian male presented to the clinic after being discharged from the emergency room (ER) due to Tianeptine use disorder and withdrawals. Having used Tianeptine for six months, he started with 150 mg/day, escalating to 9000 mg/day [picture one] within a few weeks, driven by the pursuit of opioid-like effects. Facing financial constraints, he turned to Tianeptine as a more affordable alternative to oxycodone, which he had used four years ago. Despite successfully completing a 30-day detox for oxycodone, he was now grappling with escalating Tianeptine use. The ER administered buprenorphine 8 mg off-label to manage withdrawals. Stable enough for discharge, the patient received a three-day prescription for buprenorphine 8 mg twice a day and gabapentin 300 mg three times a day for follow-up in the addiction medicine ambulatory clinic.
Three days later, the patient continued to experience withdrawal symptoms, describing sensations like bugs crawling under his skin, shaking, nervousness, stress, and palpitations. Blood pressure and heart rate remained elevated. To address these persistent symptoms, the buprenorphine dose was increased to 2.5/day, and fluoxetine 20 mg daily was initiated, along with the continued use of gabapentin. Follow-up at two weeks revealed resolution of withdrawal symptoms, and the patient reported stability on the prescribed medications with no cravings for Tianeptine or opioids.

Case 2:
The second case involves a 68-year-old male who visited the clinic after a Tianeptine overdose on top of Kratom use. He had been using Kratom for 1.5 years without adverse effects but decided to experiment with Tianeptine, resulting in respiratory depression and unresponsiveness. Initially suspected to be a stroke or seizure, it was later confirmed as an overdose. The patient, with a prior history of opioid use disorder, had been sober for five years but relapsed using Kratom to manage body aches and pain. Following the overdose, he was admitted to the ICU, intubated, given Narcan, and subsequently started on Suboxone. Discharged with a two-week supply, the patient followed up in the clinic with increased nervousness and anxiety. Buprenorphine/naloxone dose was increased from 2 mg twice a day to 4 mg twice a day. Four weeks later, the patient reported resolution of symptoms and no more cravings for opioids.

Conclusion & Discussion: Tianeptine is an atypical TCA with a novel mechanism of action by increasing the uptake of serotonin 5-HT in the brain, rather than serotonin reuptake inhibition like many antidepressants [3]. The standard dosage of treatment for patients with major depression, depressed bipolar disorder and dysthymia is typically in the range of 25 to 50 mg/day [3]. Patients who seek the psychoactive effects of Tianeptine will take supratherapeutic doses, such as the patient mentioned above, who consumed 18,000 mg a day. In a series of 18 case studies of Tianeptine toxicity, the highest dose that was taken per day was 4125 mg. [4]. Tianeptine is becoming more and more popular as a gas station drug as it is labeled as a dietary supplement to enhance mood and cognition.However, some of the effects are through opioid receptors which makes it a drug to be abused significantly. In conclusion, these cases underscore the complexities of managing Tianeptine-related issues, emphasizing the importance of comprehensive care, including medication adjustments and psychological support, to achieve successful outcomes in individuals with substance use disorders.

References: 1). Tianeptine, an Antidepressant with Opioid Agonist Effects: Pharmacology and Abuse Potential, a Narrative Review. Pain Ther. 2023 Oct;12(5):1121-1134. doi: 10.1007/s40122-023-00539-5. Epub 2023 Jul 15. PMID: 37453966; PMCID: PMC10444703.
2).From Antidepressant Tianeptine to Street Drug ZaZa: A Narrative Review. Cureus. 2023 Jun 20;15(6):e40688. doi: 10.7759/cureus.40688. PMID: 37485121; PMCID: PMC10359047.
3).Tianeptine: a review of its use in depressive disorders. CNS Drugs. 2001;15(3):231-59. doi: 10.2165/00023210-200115030-00006. PMID: 11463130.
4).Tianeptine Abuse and Dependence in Psychiatric Patients: A Review of 18 case reports in the literature
Mol Diag Ther 15, 231–259 (2001). https://doi.org/10.2165/00023210-200115030-00006