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.
Dan – for the non-toxocologists in the crowd, why is the activity against IBS a red flag? Is that because it is a common feature of opioids? (I know opioids are cause constipation and are used to treat diarrhea (imodium), but didn’t know it worked generally for IBs
You are correct. I was pointing to the constipating effects of opioids. There are no good studies I know of showing opioids are good for IBS.
For what it’s worth it appears to be only approved in France, the rest of Europe has never approved it for any endpoint.
My understanding is that it is marketed as Stablon in 15 European Union countries (France, Luxembourg, Portugal, Bulgaria, Romania, Slovakia, Poland, Malta, Hungary, Lithuania, Slovenia, Czech Republic, Austria, Latvia, and Estonia. https://www.tga.gov.au/book-page/36-tianeptine-0
Well, the more you know. I knew I should’ve checked more places 🙂
Happy to see that Sweden hasn’t approved it at least.
“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?”
Wow, this is massively patronizing. You’re actually calling things like piracetam ‘drugs that should be illegal’?
It’s as if the medical profession is trying to control every single substance that people put into their bodies. And without evidence, just labelling it with the scary word ‘drug’.
And if it’s something with vague opioid activity? You lose all trace of civility, openly taunting people and shaming them in an obnoxious, puritan manner. “You can get 10 grams of pure tianeptine for $85! Don’t you *really* want this bargain now, even if you didn’t before? No, I am not providing a link . . . shame on you, you degenerate junkie! Fight the Drug War!!”
Reading this article would actually damage mental patients’ trust in the health profession.
Tianeptine is pleiotropic; it affects not just the dopamine, serotonin, AMPA/NMDA and adenosine systems, but also some enhancing BDNF release (and therefore plasticity), and preventing stress-induced remodelling.
There is no simple answer like ‘it was an opiate all along, everything else doesn’t matter’. It is excessive to compare it to fentanyl or heroin. Tianeptine doesn’t produce tolerance or withdrawal in normal dosages. The French concluded the risk of dependence is only 1/1000 patients (it’s totally oxycodone). In 2012 they concluded the risk/benefit ratio was still positive.
“But opiate addicts are injecting it” – they do the same thing to Immodium.
Hello, perhaps you might be interested in a review of the published cases.
I gathered as much info as possible about the doses, effects and withdrawal symptoms.
https://www.tandfonline.com/doi/abs/10.1080/02791072.2018.1438687
Its a shame this medication is being abused. Its used in the country I practice in and can be effective in treatment resistant cases. As a controlled substance, it must be prescribed and monitored carefully.. I think the real problem here is not the medication, but lack of control over its distribution. A similar situations exist with psycho-stimulants which are a =second= line option after behavioral therapy in ADHD, but still available for well selected patients. Just like tianeptine, psycho-stimulants can be misused, but are no doubt useful in some cases. It would be a shame to “throw the baby out with the bathwater” in cases such as these.
Its a shame this medication is being abused. Its used in the country I practice in and can be effective in treatment resistant cases. As a controlled substance, it must be prescribed and monitored carefully.. I think the real problem here is not the medication, but lack of control over its distribution. A similar situations exist with psycho-stimulants which are a =second= line option after behavioral therapy in ADHD, but still available for well selected patients. Just like tianeptine, psycho-stimulants can be misused, but are no doubt useful in some cases. It would be a shame to “throw the baby out with the bathwater” in cases such as these.
Furthermore, psychostimulants can even result in psychosis when used as prescribed and yet they are still used. Dr. Rusyniak, I urge you to look at this medication from the other side as well. As a toxicologist, you will see the negative outcomes from misuse. Yet, there are many patients who have benefited from the medication as well.
Unfortunately, psychiatry is the most primitive of the branches of medicine with a limited set of tools available. As several major papers have shown recently, the benefits and risks of antidepressants are a matter of debate. According to Hengartner, “some patients may benefit from acute pharmacotherapy, but on average clinical benefits are debatable…. Continuation and maintenance therapy is not recommended….”
In short, tianeptine, as most psychotropics, is probably useful to have as a short term therapy when controls are in place. Effective long term treatment of psychiatric illnesses requires decades more of basic research.
References-
Moran LV, Ongur D, Hsu J, Castro VM, Perlis RH, Schneeweiss S. Psychosis with methylphenidate or amphetamine in patients with ADHD. N Engl J Med. 2019;380:1128-1138. doi: 10.1056/NEJMoa1813751.
Hengartner, M. P. (2017). Methodological flaws, conflicts of interest, and scientific fallacies: Implications for the evaluation of antidepressants’ efficacy and harm. Frontiers in Psychiatry, 8(275). https://doi.org/10.3389/fpsyt.2017.00275
I can’t believe the sheer ignorance of this post to create more hype over this drug. It creates similar effects that opiates have on the body and it’s very short lived. Yes, you are correct that they do use it in high doses, but many people use this NOW because of the fake hysteria surround the opioid crisis, which is another fake crisis in of itself. So, what does the government do when it gets control of healthcare? It completely trashed a successful platform that has worked for decades. Yes , I know some people don’t have insurance , but I’m speaking to the overall entity that is healthcare. What does the government do when they think they know more about the body than the public? They put restrictions on good medicine that has helped pain sufferers for ages. Fentanyl is being brought in mass quantities at a time. We have a border security problem which isn’t being addressed and this crap keeps coming in. People die in heroine overdoses and cocaine overdoses because it has fentanyl in it and wow suddenly we have an opioid crisis. So the governments solution ? Don’t fix the border solution – let’s just out right BAN ALL OPIATES. And let the people suffer. The millions who need it for survival. The ones who go into real surgery and now they are limited to a very tiny supply because the government is smarter than a doctor. And what about doctors who over prescribe ? Punish them but don’t certainly punish a person with real problems.
and now is point….
Every case of withdrawal from tia – it’s not TIA alone. Tia should not be objected. People might as well inject any powder laying around. That’s just stupid. Tia is 99.9 percent bio available. Anyone who uses tianeptine knows this. What killed the person except the injection cases? Alcohol, heavy benzos, oh no here it is some tia , and weed or coke. It’s always a combination of many downers. Its like making an argument to ban Pepsi. Some Jack ass decided to shoot Pepsi in his veins. Turns out he was high on acid, weed , mdma, BUT HEY LETS BAN ALL PEPSI…
Tianeptine is probably the safest drug out there that some people are abusing. Just leave them alone because if you ban this then they will find something else probably more dangerous to abuse. You will never stop people from getting high or drunk. It’s in our nature. This tianeptine is literally no more dangerous than smoking a joint. He’ll probably safer. Get off your high horse and go deal with the real problems that need to be concerned with. J
Ian, Glassrose, Absent Smith…excellent takes, all of you. People are suffering because the government decided we, as a society should basically suck it up and deal with the pain even though people have been on these meds their entire adult life. The Docs are scared sh*tless to prescribe anything now and it moved a lot of patients to either suffer, get it from the street or do their homework and try other things like Tia and kratom (which the gov is also trying hard to screw up but thankfully they‘ve been pulled back even though some states banned it). This is America last time I checked, not communist Red China. More government is NEVER the answer, less is…much less!
I take 2 to 3 grams a day and it’s great for my back pain! They made a great medication, but labeled it wrong as an antidepressant. It should be labeled as an opioid. It should be legal in the United States, and all drugs should be legal in the United States. It’s a proven fact that when you legalize drugs there’s less of a problem. The FDA is corrupt. The only reason tianeptine wasn’t brought to market in the United States is because they could not patent it. It wasn’t going to be a big money maker, and that’s a fact. Also it would take away money from all their worthless antidepressants and a bunch of other garbage medications that basically don’t even work, and they have horrible side effects. It’s all about the money with the pharmaceutical industry. The pharmaceutical industry owns the FDA!!! Corrupt corrupt corrupt!!!!
Smh. Stupidest article I’ve ever read. Once again, you’re deciding what people can and should do. If you don’t like it, don’t take it. Why is this so hard to understand?? And did you see, in your own words, that the one overdose was from an injection?? That guy deserved what he got. If he’s injecting Tianeptine, he’s also injecting heroin. And you can’t place anyone who takes it in capsules in the same category as that guy. It isn’t the same. Tianeptine has worked wonders for me, kept the opioids away, and I haven’t looked back.
Tianeptine is the best thing I ever tried for my anxiety and depression. Used at the right doses it has no opioid effects and no withdrawal or addiction. There is also rises in BDNF(brain derived neutropic factor(neurogenesis)) another indicator of reduced stress and depression.
This article is referring to very rare cases of abuse. You could abuse cheese burgers too. Such a biased stupid article.
What is wrong with you? This is the only antidepressant that worked for me and I tried almost all of them. It also soothes my anxiety. I take 12,5mg three times a day. Tianeptine helps me lead a normal life, without severe side effects unlike all the SSRIs/SNRIs out there. What this article does is scare people away from it, people who might need it as a last resort. Shame on you.
I write this in the Hope’s of others. Doing preliminary research before it’s too late. I started taking an overthe counter drug a year ago called serenity from my locale health nutrition shop.. little did I know this supplement held a drug called tianeptine as its 3rd ingredient