(136) A Case of Tianeptine Overdose Requiring ICU Admission

Background & Introduction: Tianeptine is an atypical tricyclic antidepressant that is approved in some countries for treatment of major depressive disorder [1]. It also acts as a full agonist at the mu opioid receptor. It is not approved by the Food and Drug Administration (FDA) and is under review as a controlled substance. Tianeptine has risen in popularity as a street drug over the past few years, becoming available for purchase at smoke shops and gas stations under the names “ZaZa” or “Tianna.” While tianeptine dependence, withdrawal, and overdose has been described in the literature for decades, this is largely at the level of case reports [2]. Furthermore, acute intoxication presents heterogeneously due to frequent co-ingestions and the drug’s activation of multiple receptors. In one article from a poison control center describing 17 cases of acute intoxication, 24% featured opioid-intoxication-like effects requiring naloxone, while 29% featured agitation [3]. This can make overdose complicated to identify and manage.

While tianeptine use has increased, medical knowledge and literature lag behind its potentially complicated toxidrome. More literature describing tianeptine use and toxicity is needed.

Case Description: This case report describes a patient who overdosed on tianeptine. This overdose was complicated by cardiac arrest, acute hypoxic respiratory failure requiring intubation, and possible seizures.

The patient is a 33-year-old man with a past medical history of depression, anxiety, and opioid use disorder with prior unintentional overdose. His partner noted he used tianeptine to cope with anxiety and avoid use of opioids. In the weeks prior to admission, he was using kratom and tianeptine every day. He usually bought kratom and tianeptine online, but on the day of admission he purchased a different brand of tianeptine from a new smoke shop. Notably, the product was labeled with his typical dose. Immediately after consuming the substance, he began to have difficulty breathing and then became unresponsive. A friend called emergency medical services (EMS).

Upon arrival, EMS oxygenated the patient with a bagged mask and administered naloxone, with oxygen saturation reaching 100%. He then became bradycardic, with heart rate on the monitor less than 10 beats per minute without pulse, consistent with pulseless electrical activity. He received one round of chest compressions with return of circulation to sinus tachycardia at 105 beats per minute without use of epinephrine. He was then intubated and brought to the hospital.

On presentation to the hospital, heart rate was 142 beats per minute, blood pressure was 195/104 mmHg, temperature was 96.8 Fahrenheit, with oxygen saturation 98% in the setting of mechanical ventilation. He was sedated with propofol with subsequent hypotension to nadir 80/42, for which he was started on norepinephrine. He had an episode of shaking and gaze deviation, which was treated with lorazepam. Electrocardiogram was notable for QTc 591 msec and QRS 167 msec, for which he was given 50 milliequivalents of sodium bicarbonate. CT chest showed bilateral lower lobe collapse with scattered bronchial obstructions suggestive of aspiration. Urine toxicology screen was negative. He was admitted to the intensive care unit (ICU).

In the ICU he became tremulous during propofol weaning. Spot electroencephalogram was negative for epileptiform activity. Neurology evaluation determined the tremors to be most consistent with neuromuscular agitation in the setting of his toxidrome. On day two of admission, he self-extubated and oxygenated well without further support.

By hospital day three, his toxidrome fully resolved and he was discharged home.

Conclusion & Discussion: We describe a case of tianeptine overdose leading to cardiac arrest and respiratory failure requiring intubation. Tianeptine is not FDA-regulated and is widely available for purchase without a prescription. It has increased in popularity recently, but medical literature regarding the substance remains sparse. Much of the case is consistent with a tricyclic antidepressant toxidrome, as well as possible features of opioid overdose. Fortunately, the patient improved without prolonged symptoms or disability.

This case was notable in that the patient experienced toxicity with a product labeled with his typical daily dose. Many previous cases in the literature describe toxicity with escalating doses or significant co-ingestion. The circumstances of the patient’s use are also notable in the context of the opioid crisis, as he was using tianeptine in part to avoid returning to opioid use.

While this case is not generalizable to every tianeptine overdose, our hope is that it will add to the body of medical literature on tianeptine and spread awareness of the substance and its variable toxidrome, as well as highlight patients at risk. Further research is needed to determine the best evidence-based care for tianeptine use and overdose.

References: 1. Edinoff, A. N., Sall, S., Beckman, S. P., Koepnick, A. D., Gold, L. C., Jackson, E. D., Wenger, D. M., Cornett, E. M., Murnane, K. S., Kaye, A. M., & Kaye, A. D. (2023). Tianeptine, an Antidepressant with Opioid Agonist Effects: Pharmacology and Abuse Potential, a Narrative Review. Pain and therapy, 12(5), 1121–1134. https://doi.org/10.1007/s40122-023-00539-5
2. Springer, J., & Cubała, W. J. (2018). Tianeptine Abuse and Dependence in Psychiatric Patients: A Review of 18 Case Reports in the Literature. Journal of psychoactive drugs, 50(3), 275–280. https://doi.org/10.1080/02791072.2018.1438687
3. Rushton, W., Whitworth, B., Brown, J., Kurz, M., & Rivera, J. (2021). Characteristics of tianeptine effects reported to a poison control center: a growing threat to public health. Clinical toxicology (Philadelphia, Pa.), 59(2), 152–157. https://doi.org/10.1080/15563650.2020.1781151
4. Biancarelli, D. L., Biello, K. B., Childs, E., Drainoni, M., Salhaney, P., Edeza, A., Mimiaga, M. J., Saitz, R., & Bazzi, A. R. (2019). Strategies used by people who inject drugs to avoid stigma in healthcare settings. Drug and alcohol dependence, 198, 80–86. https://doi.org/10.1016/j.drugalcdep.2019.01.037
5. Wagner, M. L., Pergolizzi, J., Jr, LeQuang, J. A. K., Breve, F., & Varrassi, G. (2023). From Antidepressant Tianeptine to Street Drug ZaZa: A Narrative Review. Cureus, 15(6), e40688. https://doi.org/10.7759/cureus.40688