Tianeptine is a drug with antidepressant and anti-anxiety effects. It has been shown to reduce depression in Parkinson’s disease and has also been shown to be effective for the treatment of asthma. However, tianeptine is potentially addicting and can lead to abuse or overdose, especially in those with a history of previous addiction.

Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

What is Tianeptine?

Tianeptine, also known as stablon, is a drug primarily used in the treatment of major depressive disorder. It has also been used to treat irritable bowel syndrome and asthma.

Tianeptine has antidepressant and anti-anxiety properties (R).

Tianeptine has a variety of effects on the body, including motivation enhancement, anxiety suppression, cognitive euphoria, focus enhancement, rejuvenation, and cognitive fatigue [R, R2].

Tianeptine was discovered and patented by the French society of Medical Research in the 1960’s. Its brand names include Stablon, Coaxil. Tatinol, Tianeurax, and Salymbra.

Tianeptine is available in European, Asian, and South American countries. It is banned in the United Kingdom and is not medically prescribed by doctors in the United States [R].

Tianeptine has challenged the monoaminergic hypothesis of depression, as well as the proposed monoaminergic mechanisms whereby the action of most known antidepressants was explained [R].

However, no one is sure exactly how tianeptine works or helps the conditions listed. The mechanisms listed are potential mechanisms by which it can help these conditions.

My Experience With Tianeptine

Tianeptine has a noticeably relaxing effect, but it also has a dopaminergic effect and my dopamine levels are very high.  A tiny dose of any dopaminergic drug such as modafinil, amphetamines or selegiline will be too much for me.  Tianeptine is no exception to that.

However, I am the exception.  The fact that tianeptine can increase dopamine function and also be anti-anxiety is very uncommon because, usually, dopamine can increase anxiety.  So tianeptine is a nice and unique mix.

When a client has anxiety and issues with SNPs of their dopamine receptors (DRD2 and DRD3), I will often mention tianeptine.

Uses of Tianeptine

1) Depressive Symptoms

Tianeptine was as effective as several classical antidepressants in patients with major depression, dysthymia or adjustment disorder. Also, extended treatment with tianeptine decreased the incidence of relapse/recurrence of depression (R).

In an open, non-comparative clinical study in patients with Parkinsons’ disease (PD), tianeptine decreased the severity of depression and also improved the quality of life in these patients (R).

In rats, tianeptine helped with drug-induced seizures and learning and memory impairment. This study shows that tianeptine may benefit depressive patients with epilepsy (R).

Tianeptine may have an additional potential for a specific subgroup of depressed patients like the elderly and those with chronic alcoholism due to a relative lack of sedative, anticholinergic and cardiovascular adverse effects (R).

Tianeptine helps depressive symptoms in postmenopausal women and may decrease appetite. However, it does not affect weight long-term and should not be used for obesity treatment (R).

Tianeptine reduces depression by:

  • Modulating the glutamate receptors, including NMDA and AMPA receptors (R, R).
  • Normalizing glutamate levels.  It reversed stress-induced increases of glutamate in the rat basolateral nucleus of the amygdala (R).
  • Potentiating AMPA receptor function in the frontal cortex (via phosphorylation of GluR1 subunits) (R).
  • Activating the Mu-opioid and delta-opioid receptors, which has antidepressive effects (R).
  • Increasing the release of BDNF (R).
  • Enhancing serotonin reuptake (R) – it helps soak up serotonin from outside of the cell, thereby increasing serotonin inside the cells (RR).
  • Enhancing the mesolimbic (pleasure center) release of dopamine and potentiating the dopamine receptors (DRD2 and DRD3 receptors) (RR).
  • Increasing the responsiveness of the α1-adrenergic system (R). A reduction in alpha-1 noradrenergic neurotransmission increases depressive behavior and likely plays a role in depressive illness (R).
  • Increasing norepinephrine (possibly).

2) Anxiety, Stress, and PTSD Symptoms

In elderly depressive patients, a drug regimen of tianeptine or escitalopram improved anxiety symptoms and subjective and objective neurocognitive functions(R).

In panic disorder patients tianeptine appeared to reduce their reaction to panic challenge (R).

In rats, tianeptine increased respiration and prevented morphine-induced respiratory depression (R).

In a multicenter study, Tianeptine (at 37.5mg dosage) was effective in treating Post-traumatic stress disorder (PTSD) patients when compared to the control (R).

In rats with predator-caused posttraumatic stress disorder (PTSD), tianeptine most effectively prevented the effects of psychosocial stress (R).

In rats given tianeptine, extinction learning and memory were increased. This indicates the tianeptine could change learning behaviors in exposure-based therapy (R).

Tianeptine has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory (R). Tianeptine blocked stress-induced memory errors in two different tasks (R).

In an experiment where maternally deprived rats were subjected to swimming and field tests, tianeptine helped them cope with stress better (decreased the immobility time and increased the swimming time) (R).

In female rats, tianeptine reduced the effect of stress+lipopolysaccharide (LPS) on BDNF levels better than desipramine and fluoxetine (antidepressants) (R).

Tianeptine, along with similar antidepressive drugs, help restore the damage on biomolecules caused by stress (R).

In stressed rats, tianeptine reversed the decrease in catalase activity caused by saline (R).

In mice, tianeptine lowers stress-caused alopecia areata (hair loss) (R).

Tianeptine reduces anxiety by:

  • Inhibiting stress-induced changes in glutamatergic neurotransmission in the hippocampus and amygdala in animal models (R, R).  It indirectly alters glutamate receptor activity, which in turn affect neural plasticity (R).
  • Normalizing glutamate levels.  It reversed stress-induced increases of glutamate in the rat basolateral nucleus of the amygdala (R) and inhibited glial glutamate transporters (R). Tianeptine prevents the stress-induced reorganization of glutamatergic synaptic vesicles in the hippocampus neurons (R).
  • Enhancing serotonin reuptake (R) – it helps soak up serotonin from outside of the cell, thereby increasing serotonin inside the cells (RR).
  • Regulating prefrontal cortical activity and HPA axis activation in male rats (R).
  • Regulating glucocorticoid receptors in areas of the brain affected by stress from maternal separation (in rats) (R).
  • Increased GABA concentration (via GAD65 expression) in the spinal cord (R).
  • Tianeptine activates adenosine A1 receptors, which might help with anxiety (based on zebrafish) (R). This receptor is activated by adenosine and also lowers heart rate.

3) Tianeptine Benefits Memory and Learning

Patients with Major Depression (N = 164) were randomly assigned to either tianeptine (37.5 mg/d) or escitalopram (an SSRI) for 12 weeks.

After 12 weeks, the tianeptine group showed significant improvement in commission errors, verbal immediate memory, Mini-Mental State Examination, delayed memory, and reasoning ability, whereas the SSRI group improved in delayed memory and reasoning ability but not in the other measures.

The treatment of Major Depression with tianeptine led to more improvements in neurocognitive functions, especially in commission errors and verbal immediate memory, compared with escitalopram. Both drugs improved subjective cognitive impairment of memory and concentration. (R).

It was shown to exert improving effects on learning as well as on working memory and on reference memory in rodents (R) and to exhibit vigilance-enhancing effects in rats (R) and monkeys (R).

A tianeptine hybrid of tacrine and tianeptine was promising in cellular models of Alzheimer’s disease (R).

4) Anti-inflammatory Effects

Tianeptine causes the suppression of lipopolysaccharide (LPS)-induced TLR4 expression. It also has anti-inflammatory benefits in microglial cells (R).

Tianeptine sodium salt suppresses TNF-α-induced MMP-9 expression via inhibition of PI3K/Akt-mediated NF-κB activity and may help prevent invasion by cancer cells (R).

5) Pain

Tianeptine has a bunch of mechanisms by which it can relieve pain.

Tianeptine decreases pain by:

  • Activating the Mu-opioid and delta-opioid receptors, which cause pain relief (R).
  • Increasing GABA concentration (via GAD65 expression)  and activating the 5-HT7 receptors in the spinal cord, which reduces neuropathic pain (R).
  • Activating adenosine A1 receptors, which causes pain relief and reduces seizures (R).
  • Through anti-inflammatory effect.
  • Increasing serotonin and norepinephrine levels in the spinal dorsal horn (R).

6) Irritable Bowel Syndrome

Serotonin plays an important role in the Enteric Nervous System in the intestinal tract, where it controls intestinal secretions and the movement of digestive material.

Increased Serotonin causes elevated secretions and movement, which contributes to pain, bloating and diarrhea in patients with Irritable Bowel Syndrome (IBS).

Tianeptine decreases serotonergic activity, and thus improves the symptoms associated with IBS and Nonulcer Dyspepsia.

In a multicenter, open-label, randomized controlled study, tianeptine was effective as the standard drug (amitriptyline) for treating IBS-D (Irritable bowel syndrome with diarrhea) patients (R).

7) Asthma

In an open study with 25,000 asthmatic patients, treatment with tianeptine provoked an abrupt disappearance of asthma attacks (R).

During asthma attacks, catecholamines and free serotonin are found circulating in the blood. Tianeptine decreases free serotonin in the blood.

It does so by enhancing serotonin uptake by platelets and serotonergic axons at the Central Nervous System.

Free serotonin is taken up by lung cells, which induces bronchial contraction (via 5-HT(3) and 5-HT(4) postsynaptic receptors) [R].

Dosage of Tianeptine

The usual dosage is 12mg 3X a day for a normal weight individual, but some people go up to 25mg at a time.

Contraindications of Tianeptine

In depressive patients with bipolar symptoms, tianeptine, and other antidepressive drugs worsened the mean scores of tests used to measure depression (R).

During pregnancy, tianeptine mimics opiates and may cause neonatal abstinence syndrome (R).

Tianeptine increased binge-drinking behaviors in adolescents but decreased overall alcohol consumption in adults (R).

Possible Side Effects and Negatives

Tianeptine’s side-effects are similar to the side-effects of other SSRI’s. These include nausea, constipation, abdominal pain, headaches, dizziness, and changes in dreaming.

Older patients should take a smaller dosage of Tianeptine, as should patients with renal failure.

Dosage does not need to be adjusted in patients with alcoholism or hepatic impairment, or patients on dialysis [R].

Liver Toxicity

Antidepressants, like tianeptine, increased the risk of liver toxicity (R).

Tianeptine Decreases Emotional Memory

Healthy volunteers were randomized to receive a single dose of tianeptine (12.5 mg) or placebo, and subsequently completed a battery of tasks measuring emotional processing, including facial expression recognition, emotional memory, and attentional vigilance, as well as working and verbal memory. Tianeptine-treated subjects were less accurate at identifying facial expressions and showed reduced memory related to emotion and reduced attentional vigilance to positive stimuli (R).

Tianeptine Warnings

It is possible to take a fatal dose of tianeptine or develop an addiction. Tianeptine may be mildly addictive, causing both physiological and psychological dependence [R, RR].

Tianeptine may cause a euphoric effect, similar to that of opioids. This effect, combined with user tolerance may compel users to take higher doses than required [R].

Tianeptine should not be taken in dosages of more than 100 mg/day.

Synergies and Drug Interactions

  • In mice, tianeptine combined with exercise exerted synergistic effects on the mouse hypothalamic-pituitary-adrenocortical (HPA) axis (R).
  • In mice, tianeptine increased sensitivity to imipramine, another antidepressive (R).
  • In mice, traxoprodil (NMDA antagonist) did not increase the effects of tianeptine (R).
  • Tianeptine does not affect melatonin levels long term in irritable bowel patients (R).

More Details on The Mechanisms by Which Tianeptine Works

  • In rats, tianeptine activates the mTORC1 signaling pathway and increases dendritic outgrowth, spine density, and synaptic proteins through mTORC1 signaling under toxic conditions in rat primary hippocampal neurons (R).
  • It normalizes the stress-induced changes in the amplitude ratio of NMDA receptor to AMPA/kainate receptor-mediated currents, which may contribute to its neuroprotective properties (R). In rats, tianeptine inhibited stress-induced re-scaling of the ratio of NMDA receptor- to AMPA/kainate receptor-mediated excitatory postsynaptic currents (R).
  • Tianeptine and other antidepressants helped reverse most changes in the insulin-like growth factor-1 of the olfactory bulb in animals (R).
  • With constant tianeptine use, there were changes in structure-dependent mitoproteome in the brains of stressed rats (R).
  • Antidepressants, such as tianeptine, may increase neuronal activity by increasing the field potential through preventing the glycine-induced ion current (R).
  • Tianeptine affects NCAM140 expression and CREB phosphorylation to cause an antidepressive effect (R).
  • Tianeptine prevented B27 deprivation-induced decreases in levels of postsynaptic density protein-95, BDNF, and synaptophysin (R).
  • Tianeptine lowered the effects of dexamethasone-caused cell viability and proliferation (R).
  • Tianeptine prevented contraction of the uterine smooth muscle and increased glutathione peroxidase and catalase activities in uteri. In contracting uteri, tianeptine decreases copper-zinc SOD activity (R).
  • Presumably, actions upstream of dopaminergic neurons are involved, such as tonic GABAergic and glycinergic inhibition of dopaminergic perikarya (RR).

Tianeptine on SelfDecode

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