Tianeptine: An Unapproved Antidepressant With Opioid-Like Effects

Tianeptine (sold abroad as Coaxil or Stablon) is an atypical tricyclic antidepressant used in Europe, Asia and Latin America. In the United States it is not approved by the Food and Drug Administration (FDA) for any medical use, and it is not a scheduled controlled substance. Studies in animals and people show it acts on opioid receptors, and case reports describe severe harm and even death from recreational use.

Visual abstract. Credit: Centers for Disease Control and Prevention.

A sharp rise in calls

CDC analyzed every tianeptine exposure call that U.S. poison control centers reported to the National Poison Data System from 2000 through 2017.

Both total calls and calls about intentional abuse or misuse rose significantly from 2014 to 2017. The authors suggest one reason: a 2014 study showed tianeptine to be an effective mu- and delta-opioid receptor agonist.

Who and how

• Callers: 198 calls (91.2%) came from health care providers.
• Sex: 177 of 215 (82.3%) involved men.
• Age: 121 of 213 (56.8%) were 21–40 years old.
• Region: the South had the most calls (75), followed by the West (54), Midwest (47) and Northeast (41).
• Route: most exposures (183) were by swallowing; 15 involved injection and 4 inhalation.
• Type: 119 (54.6%) were intentional and 29 (13.3%) involved withdrawal.
• Other drugs: among 83 calls noting another substance, the most common were phenibut (26), alcohol (13), benzodiazepines (10) and opioids (10).

Effects

Among 114 calls about tianeptine alone (excluding withdrawal), most outcomes were moderate. The main effects:

Some effects mimicked opioid toxicity, including respiratory depression in 6. Treatments included fluids (40), benzodiazepines (31), oxygen (12) and naloxone (11); 5 patients needed intubation and ventilator support. People who had taken other substances along with tianeptine were more likely to have major outcomes, and men were more likely than women to have a moderate outcome.

Withdrawal

Of 29 withdrawal calls, 21 involved tianeptine alone. The most frequent signs were agitation and nausea (each 33.3%), followed by vomiting, rapid heart rate, high blood pressure, diarrhea, tremor and sweating. Benzodiazepines (57.1%) and fluids (38.1%) were the most common treatments. Case reports describe tolerance, withdrawal resembling opioid withdrawal, naloxone reversing toxicity, and a newborn withdrawal syndrome like that seen with opioids after a mother's tianeptine dependence.

A drug sold online

Though unapproved, tianeptine is easy to buy online as a "dietary supplement" or "research chemical," and users on online forums describe its euphoric effects — and combining it with drugs such as phenibut to strengthen them. It has abuse potential among former opiate users. Abroad, regulators have acted: Georgia withdrew it from the market in June 2010, Russia and Armenia made it a controlled substance in July 2010, and Ukraine followed in January 2011. Two U.S. deaths attributed to tianeptine in people who bought it online, not reported to the poison data system, were recently reported. Amid the opioid epidemic, any new drug with opioid-like effects is a concern.

Limitations

• Reporting to poison centers is voluntary, so not every exposure was captured.
• Coding errors are possible.
• The data hold little clinical detail — nothing on response to treatment, hospital stay or lasting effects.

What providers should do

• Be alert to possible tianeptine use in patients with opioid-like overdose or withdrawal. Routine tests don't detect it, though specialty laboratories may.
• Report adverse effects to the FDA's MedWatch system.
• Call a poison control center at 1-800-222-1222 for clinical guidance.

Sources

Based on El Zahran T, Schier J, Glidden E, et al., "Characteristics of Tianeptine Exposures Reported to the National Poison Data System — United States, 2000–2017," Morbidity and Mortality Weekly Report 67(30), Centers for Disease Control and Prevention; a work of the United States government in the public domain. Original report.