Is It Safe to Mix Tianeptine With Other Drugs?

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Treatment-resistant depression is a major issue nowadays. The antidepressant drug tianeptine provides an opportunity to treat patients who do not respond to other antidepressants.

Tianeptine is a medication primarily used to treat major depressive disorder (MDD). Though its pharmacological properties are different from the typical tricyclic antidepressant (TCA), Tianeptine is still structurally classified as a TCA.

It is sometimes used for alleged nootropic properties, meaning users believe the drug improves cognition. Nootropic users frequently experiment with various substances and combinations to achieve the best brain-boosting results.

Tianeptine is also helpful in reducing the symptoms of depression-related anxiety. It is also used to alleviate irritable bowel syndrome and asthma.

Learn more about the mechanism and effects of tianeptine, and find out what happens when combined with other medications.


What is Tianeptine?

As mentioned above, Tianeptine is an antidepressant often prescribed for patients suffering from MDD and other depressive disorders.

While the use of Tianeptine is approved in Europe, Asia, and Latin America, the U.S. Food and Drug Administration (FDA) hasn’t yet approve it for any specific medical use. The available research regarding its therapeutic efficacy is still in its early stages.

However, Tianeptine is generally well-tolerated, causing only minor sedation. The neurobiological and clinical effects of tianeptine in animal models could explain its efficacy profile.

Though studies show that the drug is safe and beneficial, some users have reported becoming chemically dependent and even addicted to the substance. Others also use it to self-medicate for anxiety or depression, though doing so isn’t recommended.

How Tianeptine Affects Your Brain

Tianeptine works in the brain differently than other depression medications. Unlike other antidepressants, tianeptine acts as selective serotonin re uptake enhancer rather than an inhibitor.  

Antidepressant medications are classified as either selective serotonin reuptake inhibitors (SSRI) or monoamine oxidase inhibitors (MAOI). SSRIs affect serotonin, a chemical linked to reward and motivation and one of the main feel-good chemicals produced by your brain. 

The process by which your brain removes excess serotonin from your system is known as reuptake. SSRIs either stop or slow that process, resulting in a more pronounced, mood-lifting effect. 

Tianeptine, on the other hand, appears to increase serotonin reuptake.

The behavioral effects of antidepressant tianeptine require the mu-opioid receptor. The drug is a full agonist to two of the three types of opioid receptors. This results in opioid-like effects, such as pain relief.

Tianeptine exerts its antidepressant effects by modulating glutamate receptor activity and influencing the release of brain-derived neurotrophic factor (BDNF), both of which impact neural plasticity.

Is Tianeptine Dangerous on its Own?

Prescription pain relievers can occasionally cause pleasant euphoric symptoms in patients. But a typical dose of tianeptine will not produce a euphoric high. 

People who take tianeptine at the recommended dose do not get high, develop tolerance, or experience withdrawal symptoms.

However, in high doses, tianeptine may cause potentially life-threatening effects similar to opioid overdose. Opioid agonists, in high doses, can impair vital nervous system functions, including respiratory depression. Slow breathing is one of the most common causes of coma and death in opioid overdoses.

Can You Take Tianeptine Combinations with Other Drugs?

Tianeptine with Other Antidepressants

MAOIs are one potentially dangerous tianeptine combination. 

Both drugs have some cardiovascular effects that, when combined, might be heightened. An unsafe combination of drugs can result in hypertension, convulsions, hyperthermia, and death.

However, a 2012 study examining the potential therapeutic effects of a combination of MAOIs and tianeptine discovered that the combination could be safe and effective at the proper doses.

Tianeptine with Opioids

Opioids are a common pain reliever medication. Combining high doses of tianeptine with opioids can be fatal. A combination may result in potentiation, where one substance interacts with another to magnify its effects.

When opioids and tianeptine are combined, severe confusion, difficulty maintaining consciousness, slowed breathing, and oxygen deprivation can occur.

Tianeptine with Alcohol

Because tianeptine works in the brain as opioids, it has the potential to enhance the effects of alcohol. When the two drugs are combined, they have the potential to suppress your nervous system severely.

Alcohol does not act on opioid receptors but on gamma-Aminobutyric acid (GABA), a chemical in the brain designed to control excitability in the nervous system.

Alcohol increases the effectiveness of GABA, causing your nervous system to slow down. Opioids achieve comparable effects through different chemical processes. 

However, taking both at the same time may cause your heart rate and breathing to slow down.

Tianeptine with Benzodiazepines

Benzodiazepines are a type of medication used to treat anxiety and sleep problems. They are central nervous system depressants that work in the same way that alcohol does. Like alcohol, they are dangerous when combined with tianeptine.

When the drugs are taken together, they may potentiate each other, resulting in more profound depressive effects than when taken separately. 

Combining them may result in coma and respiratory depression.

Tianeptine with Acetaminophen

Acetaminophen—more commonly known as Tylenol—is an antipyretic and analgesic drug used alone or in combination with opioids to treat pain. It is also used for its antipyretic properties, which help to reduce fever.

Tianeptine does not work well with acetaminophen. The metabolism of tianeptine can speed up when mixed with acetaminophen.

Tianeptine with Aceclofenac

Aceclofenac is an analgesic and nonsteroidal anti-inflammatory drug (NSAID). It is used for treating osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. It has a more potent anti-inflammatory effect than traditional NSAIDs.

When aceclofenac is taken with tianeptine, it is possible to increase the risk or severity of gastrointestinal bleeding.

Tianeptine with Diphenhydramine

Diphenhydramine is widely used to treat seasonal allergies, insect bites and stings, and rashes. It also has antiemetic, antitussive, hypnotic, and anti-Parkinson effects.

Tianeptine may enhance diphenhydramine’s central nervous system depressant activities.

Tianeptine with Salbutamol

Salbutamol is commonly used to treat acute bronchospasm caused by bronchial asthma, chronic bronchitis, chronic obstructive pulmonary disease, and other chronic bronchopulmonary disorders. It is also used to prevent exercise-induced asthma.

When mixed with tianeptine, the risk or severity of hypertension may increase.

Possibility of Overdose

Tianeptine is considered a novel atypical antidepressant because it works differently from traditional antidepressants. Some researchers believe it could be a promising option for patients who have become tolerant of other forms of antidepressant treatment. 

Some studies show that tianeptine is less likely to cause tolerance or withdrawal symptoms than opioids. As a result, some users turn to the drug to treat opioid addiction.

Overdose on tianeptine is not common. But because of its direct effect on the mu-opioid receptor, tianeptine overdose can cause opioid-like effects, respiratory failure, and death. An overdose of this medication can also cause cardiotoxicity.

There is some debate about the potential consequences of abuse and misuse. Tianeptine abuse and addiction are well documented in Europe. More cases of tianeptine addiction are also being reported in the United States. The Centers for Disease Control (CDC) has reported a significant increase in tianeptine abuse or misuse reports in recent years.

In March 2018, a report was released about two cases of adult men who were found alone after taking a fatal overdose. While overdoses are common, what distinguishes this report is the drug found in their system. 

These deaths marked the first time tianeptine was linked to a fatal overdose in the United States. Although no drugs were discovered on toxicology screens, one man was known to use drugs recreationally, and the other was found with drug paraphernalia.

Tianeptine is not often used recreationally. However, in this case, the drugs were used for a purpose other than the treatment of depression.


Tianeptine is a prescription drug in the countries where it is approved. It is possible to overdose on tianeptine or develop an addiction to it. 

Tianeptine addiction can result in both physiological and psychological dependence. Only take the drug as directed by your doctor.

Self-medication and experimenting with tianeptine sodium or any kind of drug are dangerous. Always consult a doctor before taking medications. Make sure your doctor is aware of any medications, supplements, or herbs you’re taking.