Acute Toxicity From Intravenous Use of the Tricyclic Antidepressant Tianeptine

Abstract

Tianeptine (7-[([3-chloro-6,11]-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl) amino] heptanoic acid S, S dioxide) is a tricyclic compound prescribed as an antidepressant in European countries, but is not currently approved for use in the United States. There are few published case reports of tianeptine intoxication. Presented is the first case of acute toxicity associated with the intravenous use of tianeptine. A 36-year-old male intentionally injected tianeptine powder intravenously to "help him see into the future". He became unresponsive and a bystander called emergency medical services. Upon arrival to the Emergency Department, excessive constriction of the pupils, sedation, and a respiratory rate of 6 respirations per minute (rpm) were noted. Blood and urine were collected ~2 h post admission. The patient's serum ethanol concentration was 133 mg/dL. His toxicity was successfully reversed with two doses of naloxone 0.4 mg IV. He was started on a naloxone infusion at 0.2 mg/h and discharged 13 h after admittance awake, alert and oriented. The patient's urine sample screened negative for common drugs of abuse and total tricyclic antidepressants. A high performance liquid chromatography tandem mass spectrometry method was developed and validated to quantify tianeptine in urine. The calibration range was 1-100 ng/mL with linear regression correlation (r2) of 0.9996 or greater. The limit of quantitation was administratively set at 1 ng/mL. The bias of the assay was determined to be within ±20% of the target value for each quality control specimen. The intra-day and inter-day precision did not exceed 15% coefficient of variation for each quality control specimen. Matrix effects, absolute recovery, carryover and specificity were also evaluated. The patient's tianeptine urine concentration was determined to be 2 ng/mL.

In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances

“…When sold as dietary supplement, its use might even be a blind spot for early warning systems (Evans-Brown and Sedefov 2018;Griffiths, Evans-Brown, and Sedefov 2013). However, as several case reports highlight the danger of the potentially fatal misuse of tianeptine (Bakota et al 2018;Dempsey et al 2017;Proença et al 2007;Rushton et al 2020), increasing awareness is of critical importance.…”

Characteristics of Tianeptine Exposures Reported to the National Poison Data System — United States, 2000–2017

“…Several case reports showed that tianeptine toxicity mimicked opioid toxicity and that naloxone was an effective therapy ( 6 , 7 ). Tolerance to tianeptine and withdrawal have been reported ( 8 ).…”

Nursing Implications for Tianeptine Use and Misuse

“…Those with coexposures to other substances are more likely to have severe outcomes than those with tianeptine-only exposures (El Zahran et al, 2018). Case reports from the literature suggest acute toxicity from tianeptine use may be successfully treated with the use of naloxone (Ari et al, 2010; Dempsey et al, 2017).…”