Tianeptine Sulphate Dosage – The Complete Guide [2016]

Tianeptine Sulphate, Dosage, Complete Guide

 

Tianeptine is a member of the class of drugs known as tricyclic antidepressants (TCAs). It has been found to have anxiolytic and mood altering effects. Despite being a tricyclic drug, tianeptine has a significantly different pharmacologic profile than the average TCA and is thought to produce effects through action at several unique receptors. Tianeptine has found use in the treatment of asthma and irritable bowel syndrome (IBS) and may affect neural plasticity (learning).

 

Potential Benefits of Tianeptine

 

Tianeptine has been primarily used to treat depression, with some off-label use in the treatment of asthma and IBS. Following reports of improved cognition and euphoria from patients, researchers began to find that tianeptine had unique properties not seen with other TCA drugs. Subsequent research, particularly into interactions with receptors, indicates that tianeptine may dramatically affect human cognition, mood, and learning with very few side effects.

 

Depression, Stress, and Neuroplasticity

 

Neuroplasticity is a term used to describe the brain’s ability to adapt and change structure in response to learning and novel situations. In short, increased neuroplasticity is associated with easier learning and better cognitive performance while decreased neuroplasticity has opposite effects. Depression contributes to decreased neuroplasticity, so it should come as no surprise that depression impacts cognitive performance and that antidepressants can improve neuroplasticity.

 

One of the major factors contributing to depression is anxiety, which is provoked by stress. Multiple studies over many years have confirmed that stress and anxiety are detrimental to learning. Indeed, anyone who has ever been peppered with questions in a high-pressure environment (e.g. testing, medical students on wards, etc.) can attest to the cognitive impairment that results from stress. The problem is even worse than that, however. Stress can actually induce neuronal remodeling and affect established brain chemistry. There is evidence that stress, if allowed to persist, can actually lead to permanent mental impairment.

 

Antidepressants and other neuromodulatory compounds can protect against stress-induced neuronal remodeling. While the benefits of antidepressants on neuronal function have been known for some time, renewed interest has developed due to reports regarding tianeptine. There is good evidence to indicate that tianeptine inhibits pathological changes in glutamine transmission in the amygdala and hippocampus[1]. By doing this, tianeptine can reduce the effects of stress on the brain, making it easier to work in, function in, and survive high-stress environment.

 

Receptor Activation

 

Tianeptine has myriad receptor interactions that produce a wide range of effects. Beyond elevating mood and reducing anxiety, the molecule has also been found to have anticonvulsant and analgesic effects. It is also thought to induce euphoria, an effect that may explain the drug’s antidepressant effects despite a relatively mild serotonin effect.

 

What is clear about tianeptine is that it is a complex drug involved in multiple receptor interactions. Pinning down the precise effects of tianeptine as a result of specific receptor interactions has been difficult. Here is what has been discovered about the drug thus far.

 

Glutamate Receptors

Glutamate is a non-essential amino acid that plays an important role in neurotransmission and neural activation. In fact, glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system and is heavily involved in learning and memory[2]. There are several different glutamate receptors in the central nervous system (CNS), including the NMDA receptor and the AMPA receptor.

 

NDMA receptor activation plays a vital role in learning and memory as well as in alertness. Many anesthetic drugs, like ketamine and nitrous oxide, reduce NMDA receptor activity. When activity is increased, as is the case with tianeptine binding, the NMDA receptor enhances memory and learning through a Hebbian mechanism. This essentially means that it promotes synaptic development and thus enhances the formation of connections between one neuron and another.

 

AMPA receptor activation mediates fast synaptic transmission in the CNS. This effect plays a significant role in long-term potentiation (LTP), which is the process of strengthening of synapses based on recent patterns of activity. In other words, AMPA receptor activation helps to strengthen synaptic connections and thus helps to make newly learned tasks and facts more permanent. It is a factor in long-term memory formation.

 

Tianeptine alters glutamate activity at both of the above receptors and, in so doing, may boost memory and learning. It also promotes the release of brain-derived neurotrophic factor (BDNF), which promotes nerve and synapse growth and is associated with the formation of new memories and the protection of existing brain structure[3], [4]. BDNF is heavily associated with the cognitive-enhancing effects of physical activity[5].

 

Adenosine A 1  Receptors

Adenosine A 1  receptors are thought to inhibit cholinergic neurons in the basal forebrain, an effect associated with increasing sleepiness and decreased alertness[6]. The receptors have also been associated with anticonvulsant and analgesic activity. Stimulants tend to antagonize (suppress activity) A1 receptors while sedatives tend to increase activity and thus reduce seizure activity and raise seizure thresholds (i.e. the amount of aberrant brain activity needed to trigger a seizure).

 

Tianeptine appears to modify the downstream effects of A 1  receptors, which means the drug works not at the receptor itself, but by modifying the chain of events that follows after receptor activation. In so doing, tianeptine may be able to suppress seizure activity and produce analgesic effects without producing the reduction in alertness associated with these events.

 

µ-Opioid and ?-Opioid Receptors

The µ-opioid receptor is heavily associated with analgesia (pain relief) and euphoria. Morphine is the prototypical µ-opioid receptor agonist. The ?-opioid receptor is primarily associated with analgesia as well as with respiratory depression. Tianeptine is a heavy agonist of both receptors, which would explain most of the drug’s analgesic properties, but may also help to explain its anxiolytic and antidepressant effects.

 

Tianeptine appears to produce relatively few effects on serotonin and norepinephrine levels, something that sets it apart from the other TCA drugs. Its antidepressant effects are thought to relate more to its µ-opioid and ?-opioid activities. These differences may help to explain why tianeptine can be more effective in refractory depression than other TCAs and why it lacks many of the side effects typical of TCAs.

 

Monoamine Transporters

Monoamine transporters regulate levels of monoamine neurotransmitters like adrenaline, dopamine, serotonin and melatonin. Drugs that directly inhibit monoamine oxidase, an enzyme that breaks down monoamines, have been used as antidepressants in the past, but have generally been abandoned due to high rates of side effects and a vast array of adverse food and drug interactions.

 

It was originally thought that tianeptine produce its antidepressant effects by altering regulation of monoamine transmitters to alter levels of serotonin and other neurotransmitters associated with mood. It turns out that tianeptine likely has a very low affinity for monoamine transporters[7]. This hypothesis is supported by the fact that tianeptine administration has almost no effect on serotonin levels in studies on rats[8]. The lack of effect on serotonin and other monoamines further indicates that its µ-opioid and ?-opioid activities are the primary means by which tianeptine elevates mood.

 

Dopamine D 2  and D 3 Receptors

Tianeptine has no direct effects on dopamine receptors (there are five receptors in all), yet it does potentiate D­2 and D 3  receptors in the CNS system[8]. It also modestly enhances dopamine release. The combined effects result in improved mood and improved activity in the brain’s reward center. It is unclear how these effects are achieved, but they tend to mimic effects seen with early-generation TCAs (without the same side effects)[9].

 

Tianeptine Sodium vs Sulphate

 

Early production of tianeptine resulted in a sodium moiety in the TCA ring. It was originally developed and patented by the French Society of Medical Research, but has since been manufactured by Laboratories Servier SA in France, which sells tianeptine under the trade names Coaxil, Stablon, and Tatinol.

 

The production of tianeptine sulphate was a calculated move by a U.S.-based nootropic company to address the fact that tianeptine isn’t sold in many “western” markets. By changing the basic molecular structure, it is possible to skirt patent laws. In general, no company would take this risk, but it was deemed acceptable because Servier is not actively pursuing marketing of tianeptine in the United States, Australia, Canada, New Zealand, or the United Kingdom. Because the drug is effective in treating a variety of conditions, it is unclear why Servier has not pursued marketing in the lucrative “western” markets. Regardless, they have not pushed their patent protections and so it continues to be manufactured and sold as tianeptine sulphate rather than sodium to individuals who can benefit from it.

 

Anecdotal reports suggest that the sulphate form of the drug make it more effective than the sodium form. Users report gentler dose-response curves, easier dosing, less highs and lows in mood, and no crash when the drug is discontinued. There is some speculation that the more gradual onset of action of the sulphate form of the drug may make it less addictive, which is generally true for any drug[10].

 

Dosing Tianeptine

 

Tianeptine sodium is generally prescribed at a dose of 12.5 mg and taken three times per day. Unlike other TCAs and selective serotonin reuptake inhibitors (SSRIs), tianeptine doses do not need to be increased slowly and a taper when the medication is discontinued is not required.

 

Off-prescription use of tianeptine sulphate results in people using anywhere from 100 mg to 3000 mg without substantial side effects. Side effects that may occur at very high doses include anorexia, nausea, vomiting, and constipation[11]. The latter effect is a result of tianeptine’s opioid receptor activity. Withdrawal symptoms do occur, but are generally mild. The most common withdrawal symptoms include myalgia (muscle pain) and feeling cold.

 

Many people start out taking 20 mg of tianeptine sulphate twice per day (40 mg total) and then increase the dose to 60 mg total (20 mg in the morning and 40 mg in the evening). Doses up to 100 mg per day are common, while doses higher than 100 mg per day are relatively rare[12].

 

Though many users claim the drug has a slower onset of action and longer duration of action (allowing for the twice-per-day dosing), there are people who claim the opposite and find that effects last only a few hours. As with any drug, there are likely fast and slow metabolizers of tianeptine sulphate and thus some people may require more frequent dosing than others[13], [14].

 

Many people find that coming of off tianeptine sulphate is a more gradual process than what they experienced with tianeptine sodium. This allows people to re-dose before “falling off the cliff” and experiencing complete cessation of the drug’s effects.  Many people who have taken the sodium version recommend multiplying the total dose by 3.3 and then dividing that by two to get an initial twice-daily dosing of tianeptine sulphate.

 

Tianeptine Side Effects

 

The side effects of tianeptine are surprisingly limited. Compared to other TCAs and even the SSRI class of antidepressants, tianeptine is almost free of side effects. Despite its mild side effect profile, it is important not to mix tianeptine with monoamine oxidase inhibitors or other antidepressants as the combinations could be life threatening. Tianeptine should also not be mixed with anesthetics and its use should cease 24-48 prior to surgical intervention requiring anesthetics or hypnotics. Here are a few of the more common side effects associated with tianeptine.

 

  • Constipation
  • Diarrhea
  • Indigestion
  • Vomiting
  • Dry mouth
  • Fatigue
  • Insomnia
  • Changes in appetite
  • Dizziness
  • Respiratory depression
  • Sleepiness
  • Blurred vision
  • Decreased sex drive
  • Headache
  • Itching[15]

 

Summary

 

Tianeptine is a prescription drug with multiple effects. Though a member of the class of TCAs, tianeptine has a substantially different mechanism of action and a unique side-effect profile. Tianeptine has antidepressant, anxiolytic, analgesic, and cognitive enhancing effects. It is currently used in the treatment of depression, but is actively being investigated for use in several other conditions.

 

Resources

 

[1] S. Kasper and B. S. McEwen, “Neurobiological and clinical effects of the antidepressant tianeptine,” CNS Drugs, vol. 22, no. 1, pp. 15–26, 2008.

[2] R. Sapolsky, Biology and Human Behavior: The Neurological Origins of Individuality, 2nd ed. The Teaching Company, 2005.

[3] S. E. Slack, S. Pezet, S. B. McMahon, S. W. N. Thompson, and M. Malcangio, “Brain-derived neurotrophic factor induces NMDA receptor subunit one phosphorylation via ERK and PKC in the rat spinal cord,” Eur. J. Neurosci., vol. 20, no. 7, pp. 1769–1778, Oct. 2004.

[4] T. Ng, S. M. Teo, H. L. Yeo, M. Shwe, Y. X. Gan, Y. T. Cheung, K. M. Foo, M. T. Cham, J. A. Lee, Y. P. Tan, G. Fan, W. S. Yong, M. Preetha, W.-J. K. Loh, S.-L. Koo, A. Jain, G. E. Lee, M. Wong, R. Dent, Y. S. Yap, R. Ng, C. C. Khor, H. K. Ho, and A. Chan, “Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer,” Neuro-Oncol., Aug. 2015.

[5] S. Gomes da Silva and R. M. Arida, “Physical activity and brain development,” Expert Rev. Neurother., pp. 1–11, Aug. 2015.

[6] D. Elmenhorst, P. T. Meyer, O. H. Winz, A. Matusch, J. Ermert, H. H. Coenen, R. Basheer, H. L. Haas, K. Zilles, and A. Bauer, “Sleep deprivation increases A1 adenosine receptor binding in the human brain: a positron emission tomography study,” J. Neurosci. Off. J. Soc. Neurosci., vol. 27, no. 9, pp. 2410–2415, Feb. 2007.

[7] B. Haenisch and H. Bönisch, “Interaction of the human plasma membrane monoamine transporter (hPMAT) with antidepressants and antipsychotics,” Naunyn. Schmiedebergs Arch. Pharmacol., vol. 381, no. 1, pp. 33–39, Jan. 2010.

[8] B. S. McEwen, S. Chattarji, D. M. Diamond, T. M. Jay, L. P. Reagan, P. Svenningsson, and E. Fuchs, “The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation,” Mol. Psychiatry, vol. 15, no. 3, pp. 237–249, Mar. 2010.

[9] “Effect of repeated treatment with tianeptine and fluoxetine…?: Behavioural Pharmacology,” LWW. [Online]. Available: http://journals.lww.com/behaviouralpharm/Fulltext/2002/03000/Effect_of_repeated_treatment_with_tianeptine_and.4.aspx. [Accessed: 14-Sep-2015].

[10] “Tianeptine Sulfate is VASTLY SUPERIOR to Tianeptine Sodium • /r/Nootropics,” reddit. [Online]. Available: https://www.reddit.com/r/Nootropics/comments/30w63b/tianeptine_sulfate_is_vastly_superior_to/. [Accessed: 14-Sep-2015].

[11] P. Vandel, W. Regina, B. Bonin, D. Sechter, and P. Bizouard, “[Abuse of tianeptine. A case report],” L’Encéphale, vol. 25, no. 6, pp. 672–673, Dec. 1999.

[12] “Tianeptine Sulfate – post your dose? • /r/Nootropics,” reddit. [Online]. Available: https://www.reddit.com/r/Nootropics/comments/34vjs2/tianeptine_sulfate_post_your_dose/. [Accessed: 14-Sep-2015].

[13] “Ceretropic Stocks Tianeptine Sulphate • /r/Nootropics,” reddit. [Online]. Available: https://www.reddit.com/r/Nootropics/comments/2z4e8w/ceretropic_stocks_tianeptine_sulphate/. [Accessed: 14-Sep-2015].

[14] “Anyone tried the new tianeptine sulfate? • /r/Nootropics,” reddit. [Online]. Available: https://www.reddit.com/r/Nootropics/comments/2zobah/anyone_tried_the_new_tianeptine_sulfate/. [Accessed: 14-Sep-2015].

[15] “Coaxil Drug Information – uses, side effects, precaution for Coaxil.” [Online]. Available: http://www.diseasesatoz.com/medications/coaxil.htm. [Accessed: 21-Aug-2015].