Tianeptine Sodium: Potentially Lethal?

Tianeptine Sodium: A Nootropic With Potentially Lethal Consequences

To the Editor: In recent years, “nootropics” have become increasingly popular drugs and supplements accessible from internet resources and used to enhance mood and cognitive functioning, often without medical consultation.1 Some nootropics, eg, tianeptine sodium, are medications prescribed in other countries but have not received US Food and Drug Administration approval for use in the United States. The international sale of nootropic agents is growing; estimated sales approach 1 billion US dollars annually.2 We describe a patient whose use of tianeptine led to unintended life-threatening consequences.

Case report. A 42-year-old man displayed shallow and variable breathing; he was unresponsive to his wife’s attempts at arousal. In the ambulance, he was administered naloxone 0.8 mg intravenously, to which he responded with arousal and improved respiration. A second dose was administered, resulting in improved alertness and spontaneous respirations. He was admitted to the hospital and treated for aspiration pneumonia; his toxicology screen was positive for opioids and benzodiazepines.

He reported taking tianeptine for chronic back pain but acknowledged using more than he customarily would. He had done so unwittingly in combination with his usual alprazolam dose. He indicated, and his wife corroborated, that he had not intended to end his life but to manage pain.

He endorsed dysphoria related to back pain but denied neurovegetative symptoms of depression. He also denied a history of anxiety or mania and was able to reality test.

He said no doctor would give him anything for pain due to a remote history of illicit substance use. He discovered tianeptine sodium from internet blogs, advocating its usefulness for pain. He was able to inexpensively acquire it online (eg, from Amazon).

Subjectively, he maintained that tianeptine induced euphoria and a “sense of calm.” “You take one scoop of the powder whenever you just feel bad,” he said. However, the effects of tianeptine were short-lived. He reported tolerance, needing larger doses over time to achieve the same desired effects. Believing it was harmless, he had taken an inordinately large amount of tianeptine, prompting this hospitalization.

He was receptive to education, acknowledging the life-threatening potential of tianeptine use; he no longer intended to use it. He was discharged home in stable condition. Outpatient psychiatric and chemical dependency-based treatment were arranged to reinforce abstinence and relapse prevention and address pain-related distress.

This case illustrates the misuse and abuse potential of tianeptine sodium, an atypical antidepressant structurally similar to tricyclic antidepressants, marketed for use in Europe and Asia. It acts by serotonergic augmentation but without marked anticholinergic effects.3 Tianeptine sodium is not associated with cognitive, psychomotor, or cardiovascular effects encountered with tricyclic overdose as manifest in the present case.

Additionally, tianeptine has demonstrated opioid agonist influences,4 enhancing its appeal and potential for misuse. A review of the literature suggested that there is an abuse potential associated with tianeptine,5 consequently, it has been classified as a controlled substance in several countries. With the implementation of prescription monitoring programs and regulatory measures to prevent opioid misuse within the United States, those seeking opioids may resort to internet sites to surreptitiously acquire (and use) tianeptine or related compounds.

Internet blogs6,7 discuss the extramedical (ie, recreational) use of tianeptine and management of withdrawal. Tianeptine is available in tablet, capsule, and powder form and is accessible from online commercial sources under the rubric of nootropics. Ingestion of amounts (250-1,000 mg) exceeding the recommended daily antidepressant dose (37.5 mg) has been advocated on internet blogs6,7 to achieve opioid-like effects. Although tianeptine has not been demonstrated to cause tolerance in rodent models,8 anecdotal reports from internet blogs6,7 seem to suggest that higher doses are necessary to acquire euphoric effects over time, as illustrated in this case.

Additionally, animal models suggest that tianeptine does not produce respiratory depression, at least at doses comparable to those employed for clinical purposes.9 Nonetheless, tianeptine seems to have induced respiratory depression in this patient, which is supported by the naloxone reversal, perhaps because our patient was using vastly higher doses than are recommended clinically. The concurrent use of alprazolam with tianeptine may have resulted in synergistic effects that contributed to his respiratory depression. Overdose of tianeptine has resulted in 2 deaths,10,11 but only 1 of those was directly related to tianeptine toxicity.9 Cases12,13 of tianeptine overdose were reversible with naloxone, as in the present case.

Extramedical tianeptine use is potentially associated with severe health risks. Clinicians should entertain the possibility that use of such agents acquired from internet resources can confound the clinical presentation and complicate management of their patient’s condition.

References

1. Lanni C, Lenzken SC, Pascale A, et al. Cognition enhancers between treating and doping the mind. Pharmacol Res. 2008;57(3):196-213. PubMed CrossRef

2. Chinthapalli K. The billion dollar business of being smart. BMJ. 2015;351:h4829. PubMed CrossRef

3. Wagstaff AJ, Ormrod D, Spencer CM. Tianeptine: a review of its use in depressive disorders. CNS Drugs. 2001;15(3):231-259. PubMed CrossRef

4. Gassaway MM, Rives ML, Kruegel AC, et al. The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. Transl Psychiatry. 2014;4(7):e411. PubMed CrossRef

5. Lôo H, Ganry H, Dufour H, et al. Long-term use of tianeptine in 380 depressed patients. Br J Psychiatry suppl. 1992;(15):61-65. PubMed

6. Reddit Nootropics. My usage and review of tianeptine. https://www.reddit.com/r/Nootropics/comments/377ic6/my_usage_and_review_of_tianeptine/. Accessed June 25, 2018.

7. Bluelight. Tianeptine-inexperienced-opiate buzz. http://www.bluelight.org/vb/threads/404602-Tianeptine-Inexpereinced-Opiate-Buzz. Accessed June 25, 2018.

8. Samuels BA, Nautiyal KM, Kruegel AC, et al. The behavioral effects of the antidepressant tianeptine require the mu-opioid receptor. Neuropsychopharmacology. 2017;42(10):2052-2063. PubMed CrossRef

9. Cavalla D, Chianelli F, Korsak A, et al. Tianeptine prevents respiratory depression without affecting analgesic effect of opiates in conscious rats. Eur J Pharmacol. 2015;761:268-272. PubMed CrossRef

10. Pélissier-Alicot AL, Gavaudan G, Bartoli C, et al. Planned complex suicide: an unusual case. J Forensic Sci. 2008;53(4):968-970. PubMed CrossRef

11. Proença P, Teixeira H, Pinheiro J, et al. Fatal intoxication with tianeptine (Stablon). Forensic Sci Int. 2007;170(2-3):200-203. PubMed CrossRef

12. Ari M, Oktar S, Duru M. Amitriptyline and tianeptine poisoning treated by naloxone. Hum Exp Toxicol. 2010;29(9):793-795. PubMed CrossRef

13. Dempsey SK, Poklis JL, Sweat K, et al. Acute toxicity from intravenous use of the tricyclic antidepressant tianeptine. J Anal Toxicol. 2017;41(6):547-550. PubMed CrossRef

Simon Lucaj, MDa

Raphael J. Leo, MA, MDa

Rleomd@aol.com

aDepartment of Psychiatry, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York

Potential conflicts of interest: None.

Funding/support: None.

Patient consent: Permission was received from the patient to publish this case, and information has been de-identified to protect anonymity.

Published online: July 19, 2018.

Prim Care Companion CNS Disord 2018;20(4):17l02205

To cite: Lucaj S, Leo RJ. Tianeptine sodium: a nootropic with potentially lethal consequences. Prim Care Companion CNS Disord. 2018;20(4):17l02205.’ ©

To share: https://doi.org/10.4088/PCC.17l02205

© Copyright 2018 Physicians Postgraduate Press, Inc.