Tianeptine is a drug with antidepressant and anti-anxiety effects. It has been shown to improve the symptoms of depression and beneficial in the treatment of asthma. However, tianeptine is potentially addictive and can lead to abuse or overdose, especially in those with a history of previous addiction.
Disclaimer: This post is not a recommendation or endorsement for the use of tianeptine. The FDA has not approved this drug for any specific medical or other use, and the available research on it is still in a very early stage, without adequate data to come to any firm conclusions about its general efficacy or safety in human users. We have written this post for informational purposes only, and our goal is solely to inform people about what science currently says about tianeptine’s mechanisms, potential effects, and possible side-effects.
What Is Tianeptine?
Tianeptine is a drug primarily used to improve the symptoms of major depressive disorder (MDD). It has also been used to help irritable bowel syndrome and asthma.
Tianeptine has antidepressant and anti-anxiety properties [1].
Tianeptine has a variety of effects on the body, including motivation enhancement, anxiety suppression, cognitive euphoria, focus enhancement, rejuvenation, and cognitive fatigue [2, 3].
Tianeptine was discovered and patented by the French society of Medical Research in the 1960s. Its brand names include Stablon, Coaxil, Tatinol, Tianeurax, and Salymbra.
Tianeptine is available in some European, Asian, and South American countries. However, it is banned in the United Kingdom, and is not medically prescribed by doctors in the United States due to concerns over its potential for abuse and addiction [4].
Tianeptine has challenged the monoaminergic hypothesis of depression, as well as the proposed monoaminergic mechanisms whereby the action of most known antidepressants was explained [5].
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.
Proposed Mechanisms for Tianeptine in Depression
- Modulating the glutamate receptors, including NMDA and AMPA receptors [6].
- Normalizing glutamate levels. It reversed stress-induced increases of glutamate in the rat basolateral nucleus of the amygdala [7].
- Potentiating AMPA receptor function in the frontal cortex (via phosphorylation of GluR1 subunits) [5].
- Activating the Mu-opioid and delta-opioid receptors, which has antidepressive effects [8].
- Increasing the release of BDNF [6].
- Enhancing serotonin reuptake [9] – it helps soak up serotonin from outside of the cell, thereby increasing serotonin inside the cells [10, 11].
- Enhancing the mesolimbic (pleasure center) release of dopamine and potentiating the dopamine receptors (DRD2 and DRD3 receptors) [12, 13].
- Increasing the responsiveness of the α1-adrenergic system [14]. A reduction in alpha-1 noradrenergic neurotransmission increases depressive behavior and likely plays a role in depressive illness [15].
- Increasing norepinephrine (possibly).
Proposed Mechanisms for Tianeptine in Anxiety and Stress
- Inhibiting stress-induced changes in glutamatergic neurotransmission in the hippocampus and amygdala in animal models [16, 17]. It indirectly alters glutamate receptor activity, which in turn affects neural plasticity [6].
- Normalizing glutamate levels. It reversed stress-induced increases of glutamate in the rat basolateral nucleus of the amygdala [7] and inhibited glial glutamate transporters [18]. Tianeptine prevented the stress-induced reorganization of glutamatergic synaptic vesicles in the hippocampus neurons [5].
- Enhancing serotonin reuptake [9] – it helps soak up serotonin from outside of the cell, thereby increasing serotonin inside the cells [10, 11].
- Regulating prefrontal cortical activity and HPA axis activation in male rats [19].
- Regulating glucocorticoid receptors in areas of the brain affected by stress from maternal separation (in rats) [20].
- Increased GABA concentration (via GAD65 expression) in the spinal cord [21].
- Tianeptine activates adenosine A1 receptors, which might help with anxiety (based on zebrafish) [22]. This receptor is activated by adenosine and also lowers heart rate.
More Details on The Mechanisms by Which Tianeptine Works
- In rats, tianeptine activated the mTORC1 signaling pathway and increased dendritic outgrowth, spine density, and synaptic proteins through mTORC1 signaling under toxic conditions in rat primary hippocampal neurons [23].
- 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 [5]. In rats, tianeptine inhibited stress-induced re-scaling of the ratio of NMDA receptor- to AMPA/kainate receptor-mediated excitatory postsynaptic currents [17].
- Tianeptine and other antidepressants helped reverse most changes in the insulin-like growth factor-1 of the olfactory bulb in animals [24].
- With constant tianeptine use, there were changes in structure-dependent mitochondrial proteome in the brains of stressed rats [25].
- Antidepressants, such as tianeptine, may increase neuronal activity by increasing the field potential through preventing the glycine-induced ion current [26].
- Tianeptine induces NCAM140 expression and CREB phosphorylation [27].
- Tianeptine prevented B27 deprivation-induced decreases in levels of postsynaptic density protein-95, BDNF, and synaptophysin [28].
- Tianeptine lowered the effects of dexamethasone-caused cell viability and proliferation [29].
- Tianeptine prevented contraction of the uterine smooth muscle and increased glutathione peroxidase and catalase activities. In contracting uteri, tianeptine decreases copper–zinc SOD activity [30].
- Presumably, actions upstream of dopaminergic neurons are involved, such as tonic GABAergic and glycinergic inhibition of dopaminergic perikarya [31, 32].
Uses of Tianeptine
Effective for:
In those countries where it is approved, tianeptine is mainly used for depression and anxiety disorders, although some doctors may prescribe it for other conditions such as asthma and IBS. If your doctor prescribes you tianeptine, follow your treatment plan carefully. Never change the dose or discontinue the medication without discussing it with your doctor.
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 [33].
In a clinical trial on 18 people with Parkinsons’ disease (PD), tianeptine decreased the severity of depression and also improved the quality of life in these patients [34].
In rats, tianeptine helped with drug-induced seizures and learning and memory impairment. This study shows that tianeptine may benefit depressive patients with epilepsy [35].
Tianeptine may have 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 [33].
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 [36].
2) Anxiety, Stress, and PTSD Symptoms
In a clinical trial on 164 elderly, depressive patients, a drug regimen of tianeptine or escitalopram improved anxiety symptoms and subjective and objective neurocognitive functions [37].
In another trial on 20 panic disorder patients, tianeptine appeared to reduce their reaction to panic challenge [38].
In a study on 90 people, tianeptine (at 37.5 mg dosage) was effective in treating post-traumatic stress disorder (PTSD) patients when compared to the control [39].
In rats with predator-caused posttraumatic stress disorder (PTSD), tianeptine most effectively prevented the effects of psychosocial stress [40].
In rats, tianeptine increased respiration and prevented morphine-induced respiratory depression [41].
In rats given tianeptine, extinction learning and memory were increased. This indicates the tianeptine could change learning behaviors in exposure-based therapy [42].
Tianeptine has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory. In rats, tianeptine blocked stress-induced memory errors in two different tasks [43, 44].
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) [45].
In female rats, tianeptine reduced the effect of stress+lipopolysaccharide (LPS) on BDNF levels better than desipramine and fluoxetine (antidepressants) [46].
Tianeptine, along with similar antidepressant drugs, helped restore the damage on biomolecules caused by stress in mice [47].
In stressed rats, tianeptine reversed the decrease in catalase activity caused by saline [48].
In mice, tianeptine lowered stress-caused hair loss (alopecia areata) [49].
3) Asthma
During asthma attacks, catecholamines and free serotonin are found circulating in the blood. Tianeptine decreases free serotonin in the blood by enhancing serotonin uptake by platelets and serotonergic brain cells. Free serotonin is taken up by lung cells, which induces bronchial contraction (via 5-HT(3) and 5-HT(4) postsynaptic receptors) [50].
In a clinical trial on 25,000 asthmatic patients, treatment with tianeptine provoked an abrupt disappearance of asthma attacks [51].
In another trial on 69 asthmatic children, tianeptine improved lung function and reduced free serotonin levels [52]
4) Irritable Bowel Syndrome
Serotonin plays an important role in the nervous system of 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 clinical trial on 122 people, tianeptine was effective as the standard drug (amitriptyline) for treating IBS-D (irritable bowel syndrome with diarrhea) [53].
In another trial on 100 people with either IBS-D or IBS-C (irritable bowel syndrome with constipation), tianeptine improved the symptoms and quality of life in both groups, especially IBS-C [54].
Insufficient Evidence for:
1) Improving Memory and Learning
In a clinical trial on 164 people with major depression, patients 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 [55].
It was shown to exert improving effects on learning as well as on working and reference memory in rodents [56] and to exhibit vigilance-enhancing effects in rats [57] and monkeys [58].
A tianeptine hybrid of tacrine and tianeptine was promising in cellular models of Alzheimer’s disease [59].
A single clinical trial and some animal research cannot be considered conclusive evidence that tianeptine improves memory and learning until further clinical research is conducted.
Animal and Cell Research (Lack of Evidence)
No clinical evidence supports the use of tianeptine for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed should not be interpreted as supportive of any health benefit.
1) Inflammation
Tianeptine causes the suppression of lipopolysaccharide (LPS)-induced TLR4 expression. It also has anti-inflammatory benefits in microglial cells [60].
In rats with gum disease, tianeptine altered the inflammatory response (by changing the production of different cytokines), resulting in a decreased jawbone loss [61, 62].
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 [63].
2) Pain
Tianeptine has several mechanisms by which it can relieve pain:
- Activating the Mu-opioid and delta-opioid receptors, which cause pain relief [8].
- Increasing GABA concentration (via GAD65 expression) and activating the 5-HT7 receptors in the spinal cord, which reduces neuropathic pain [21].
- Activating adenosine A1 receptors, which causes pain relief and reduces seizures [64].
- Through anti-inflammatory effect.
- Increasing serotonin and norepinephrine levels in the spinal dorsal horn [65].
Using Tianeptine
Dosage
In those countries where it is approved, tianeptine is a prescription-only medication. Take it only as recommended by your doctor.
The usual dosage is 12 mg 3 times a day for a normal weight individual, but some people go up to 25 mg at a time (three times a day).
Side Effects
Tianeptine’s side-effects are similar to the side-effects of SSRI’s. These include nausea, constipation, abdominal pain, headaches, dizziness, and changes in dreaming. Consult your doctor if you experience severe or mild, persistent adverse effects after taking tianeptine.
Older patients should take a smaller dosage of tianeptine, as should patients with kidney failure.
Dosage does not need to be adjusted in patients with alcoholism or hepatic impairment, or those on dialysis [66].
Liver Toxicity
Antidepressants, like tianeptine, may increase the risk of liver toxicity [67].
Emotional Memory
Forty 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 [68].
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. People buying tianeptine supplements online are more likely to exceed the recommended dose or take it too frequently [69, 70, 71].
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 [71].
Tianeptine should not be taken in dosages of more than 100 mg/day.
Contraindications
In depressive patients with bipolar symptoms, tianeptine, and other antidepressive drugs worsened the mean scores of tests used to measure depression [72].
During pregnancy, tianeptine mimics opiates and may cause neonatal abstinence syndrome [73].
Tianeptine increased binge-drinking behaviors in adolescents but decreased overall alcohol consumption in adults [74].
Drug Interactions
To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. Talk to your healthcare provider to find out how tianeptine might interact with something else you are taking.
