by Dan Rusyniak
At my poison center we have seen an increasing number of a calls related to a drug I had never heard of – Tianeptine. Tianewhat? Yes, I thought the same. Although I had not heard of it, this is a drug that has been around since the 1970’s. Synthesized in the 60’s by the French Society of Medical Research, it was approved in France and other European countries under the brand names of Stablon™ and Coaxil™. It has never been approved in the US – woohoo FDA! It was a prescribed for the treatment of depression and anxiety, which makes sense since it has a similar tricyclic backbone to other well-known antidepressants (Figure modified from Wikipedia – woohoo structures!) But there was something weird about this antidepressant, it didn’t seem to work like the others.
What was different? For one, it seemed to work a lot faster than most antidepressants. Patients reported improved symptoms within days instead of weeks. Another big difference is that it didn’t seem to work by blocking monoamine reuptake transporters. So, no SSRI or SNRI effects. But patients liked it nonetheless. It seemed to help with depression, reduced anxiety, improved PTSD symptoms, and relieved irritable bowel symptoms (that should have been a red flag right there. . .) Scientists were perplexed as to how this drug worked. There was some evidence that it affected glutamate neurotransmission, and some that it worked on adenosine receptors. Or, maybe it worked through dopamine or by doing the opposite of SSRIs – enhancing the reuptake of serotonin?1,2 Nobody really seemed to know why this drug had antidepressant effects. Then in 2014, researchers looking for the mechanism of the drugs action screened it for binding and activity at a variety of different receptors. What they found was that tianeptine was a mu agonist3; an effect that might actually be behind its antidepressant effect.4 That’s right, tianeptine worked as an agonist at the same receptor in the brain as heroin, fentanyl, and oxycodone. No wonder patients liked it.
While there had been a few reports of tianeptine abuse prior to 2014, it was after the publication that it was a mu agonist that cases really started to mount; yes drug dealers read the scientific literature.5,6 In 2016, a 27-yo-male overdosed on tianeptine with predictable mu opioid effects: small pupils, slow respirations, and coma (AJRCCM 2016). Equally predictable, he woke up after 0.4 mg naloxone (he required another dose a few hours later). In 2017, a 36-year-old in Virginia injected tianeptine with similar results.7 I mentioned at the start that we have seen an increasing number of cases. All of these were similar to the case reports. Patients using tianeptine as a drug of abuse present with a classic opioid toxidrome. And my poison center is not alone. Since 2014 there has been a dramatic increase in calls to poison centers regarding tianeptine.8,9 Tianeptine abusers who abruptly stop can also develop a withdrawal syndrome similar to opioid abstainers.10 And, sadly, tianeptine abuse also seems to carry the same neonatal risks as opioids – there is a reported case of neonatal abstinence syndrome from tianeptine.11
What about the other TCA effects? Do patients who overdose on this get a prolonged QRS and QTc, do they seize, do they get anticholinergic? Those are great questions. I am so glad you asked. The short answer is NO, this has not been reported. Although it shares a TCA structure, this drug appears not to have the sodium channel blocking effects (wide QRS), potassium channel blocking effects (prolonged QTc), anticholinergic effects, or proconvulsant effects. It should be said with caution, however, that there are very few cases of overdose in the literature to date. It is possible that these effects could occur in larger doses.
Lastly, if this drug is not approved for use in the US, then how are people getting it? Are they flying to Europe to buy it? Don’t be silly, that is what the Internet is for. Yes, you can buy this stuff in large quantities on the internet. Just Google it. For instance, you can get 10 grams (10,000 mg) of pure tianeptine for $85 by clicking a button on your computer (and no, I am not providing a link . . . shame on you!) The antidepressant dose is 12.5 mg twice daily. Most people seem to abuse it at doses of up to ~100mg (check out Reddit for more experiences). So, for $85 you can get 100 doses. That is a really cheap high. And that scares the heck out of me.
What does this mean for all of you? Just that, as the opioid crisis continues, and people are looking for alternatives, we are likely to see an increasing number of overdoses from this drug. Treatment is the same as any opioid overdose. It responds to naloxone, but can require more than one dose. So along with asking about IV use, prescription drugs and alternative agents with your opioid patients, make sure you ask about “tia” (its street name) or online nootropics. What is a nootropic? It’s just a stupid name for a drug that should not be sold on the Internet, but is. Why is it legal to sell this stuff on the Internet? Because the companies that sell it make sure to state that the drug is not for human consumption. This circumvents the 1986 Federal Controlled Substance Analogue Enforcement Act and why Internet tianeptine is labeled “not human consumption”.12 If only we would listen, then we wouldn’t need tianeptine to feel better again.