Tianeptine

Usage

• Tianeptine is prescribed for major depressive episodes. In some countries, it is also used for anxiety, irritable bowel syndrome, and asthma, although evidence for these uses is less robust.
• Pharmacological Classification: Atypical antidepressant, also classified as a selective serotonin reuptake enhancer (SSRE) and an atypical opioid agonist.
• Mechanism of Action: Tianeptine enhances serotonin reuptake in the synapses, unlike traditional antidepressants that block reuptake. Additionally, it modulates glutamate receptor activity and acts as an atypical agonist at mu-opioid receptors. This complex mechanism helps improve mood and alleviate depressive symptoms.

Alternate Names

• International/Regional Variations: Tianeptine sodium, tianeptine sulfate.
• Brand Names: Stablon, Coaxil, Tatinol, ZaZa (street drug name), Tianna Red (street drug name).

How It Works

• Pharmacodynamics: Tianeptine’s antidepressant, anxiolytic, and potential analgesic and anticonvulsant effects are attributed to its combined influence on serotonin reuptake enhancement, glutamate modulation, and opioid receptor activity. Unlike many tricyclic antidepressants, it has minimal cardiovascular, anticholinergic (e.g., dry mouth, constipation), or sedative effects.
• Pharmacokinetics:
  • Absorption: Tianeptine exhibits near-complete oral bioavailability (around 99%).
  • Metabolism: Hepatic metabolism through β-oxidation. Notably, it does not involve the CYP450 enzyme system, minimizing drug interactions.
  • Elimination: Primarily renal excretion. The elimination half-life is short, approximately 2.5-3 hours in adults, increasing to 4-9 hours in the elderly.
• Mode of Action: Primarily enhances serotonin reuptake, reducing serotonin levels in the synaptic cleft. This is in contrast to most antidepressants that block reuptake. Additionally, it acts as a full agonist at mu-opioid receptors and weakly at delta-opioid receptors, potentially contributing to analgesic effects. Tianeptine also modulates glutamate receptor activity and affects neuroplasticity.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Enhances serotonin reuptake, atypical agonist of mu-opioid receptors, modulates glutamate activity.
• Elimination Pathways: Predominantly renal excretion, with hepatic metabolism via β-oxidation without CYP450 involvement.

Dosage

Standard Dosage

Adults:

• 12.5 mg orally, three times a day (37.5 mg/day total), taken with meals.
• Some sources mention a flexible dose of 25-50 mg/day, depending on clinical response.

Children:

• Tianeptine is generally not recommended for use in children under 18.

Special Cases:

• Elderly Patients: Reduced dosage of 12.5 mg twice daily or 25 mg/day total is recommended due to altered pharmacokinetics.
• Patients with Renal Impairment: Reduce the total daily dose to 25 mg.
• Patients with Hepatic Dysfunction: In severe cirrhosis (Child-Pugh Class C), reduce the total daily dose to 25 mg.
• Patients with Comorbid Conditions: Caution is advised in patients with bipolar disorder, a history of substance use disorder, seizure disorders, or cardiovascular disease. Careful monitoring and dose adjustment may be necessary.

Clinical Use Cases Tianeptine is primarily indicated for major depressive disorder. Its use in other clinical settings like those mentioned below is not established, and there’s a lack of robust clinical evidence for these applications.

• Intubation: No specific dosage recommendations.
• Surgical Procedures: Discontinue 24-48 hours prior to elective surgery.
• Mechanical Ventilation: No specific dosage recommendations.
• Intensive Care Unit (ICU) Use: No specific dosage recommendations. Dose adjustments based on renal and hepatic function may be required.
• Emergency Situations: No established role in emergency medicine.

Dosage Adjustments

• Dose adjustments are necessary for elderly patients, those with renal or hepatic impairment, and individuals with certain comorbid conditions (as noted above).
• Genetic polymorphisms affecting drug metabolism are not well studied; however, the absence of CYP450 involvement simplifies this issue.

Side Effects

Common Side Effects

• Headache, dizziness, drowsiness, nausea, dry mouth, constipation, abdominal pain, insomnia, asthenia/fatigue.

Rare but Serious Side Effects

• Hepatotoxicity (rare), severe muscle aches, cardiac arrhythmias, chest pain, blurred vision, difficulty urinating, allergic reactions, worsening of depression or anxiety, suicidal ideation.

Long-Term Effects

• Potential for dependence and withdrawal symptoms (similar to opioid withdrawal) with chronic high-dose use.

Adverse Drug Reactions (ADR)

• Serious ADRs include hepatotoxicity, cardiac arrhythmias, serotonin syndrome (if combined with serotonergic drugs), and neuroleptic malignant syndrome (if combined with antipsychotics). These necessitate immediate medical intervention.

Contraindications

• Hypersensitivity to tianeptine.
• Concurrent use of MAOIs.
• Children and adolescents under 18 years.
• Pregnancy and breastfeeding (due to limited safety data).

Drug Interactions

• MAOIs: Contraindicated due to the risk of serotonin syndrome.
• CNS Depressants (e.g., alcohol, benzodiazepines, opioids): Enhanced sedation and respiratory depression may occur.
• Serotonergic Drugs (e.g., SSRIs, SNRIs, triptans): Increased risk of serotonin syndrome.
• Alcohol: Reduces tianeptine absorption and can increase the risk of adverse effects.
• Grapefruit juice and St. John’s Wort: May increase tianeptine levels.
• Other potential interactions exist; consult comprehensive drug interaction resources for detailed information.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Limited data available, generally considered unsafe due to potential for fetal opioid dependence.
• Breastfeeding: It’s unknown if tianeptine is excreted in breast milk; safer alternatives are recommended.

Drug Profile Summary

• Mechanism of Action: Enhances serotonin reuptake, mu-opioid receptor agonist, glutamate modulator.
• Side Effects: Headache, dizziness, drowsiness, nausea, dry mouth, constipation, abdominal pain, dependence, withdrawal symptoms (with high doses), hepatotoxicity (rare).
• Contraindications: Hypersensitivity, concurrent MAOI use, pregnancy, breastfeeding, age <18 years.
• Drug Interactions: MAOIs, CNS depressants, serotonergic drugs, alcohol, grapefruit juice, St. John’s Wort.
• Pregnancy & Breastfeeding: Not recommended.
• Dosage: Adults: 12.5 mg TID (or 25-50 mg/day). Elderly/Renal Impairment: 25 mg/day.
• Monitoring Parameters: Liver function tests (periodically), monitor for signs of opioid dependence and withdrawal, assess mood and suicidal ideation regularly.

Popular Combinations Not Applicable. Due to the potential for misuse and opioid-like effects, combination therapy with tianeptine should be approached with extreme caution, and the risks and benefits should be carefully evaluated on a case-by-case basis.

Precautions

• General Precautions: Screen for allergies, substance use disorder, renal/hepatic dysfunction, and cardiac conditions.
• Specific Populations: See Dosage section.
• Lifestyle Considerations: Avoid alcohol and other CNS depressants. Caution with driving or operating machinery due to potential drowsiness.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Tianeptine?

A: The standard adult dose is 12.5 mg three times daily (37.5 mg/day total). The elderly and those with renal impairment should take a reduced dose of 25 mg/day.

Q2: What are the common side effects of tianeptine?

A: Common side effects include headache, dizziness, drowsiness, nausea, dry mouth, constipation, and abdominal pain.

Q3: How does tianeptine differ from traditional antidepressants like SSRIs?

A: Tianeptine enhances serotonin reuptake, whereas SSRIs inhibit serotonin reuptake. Tianeptine also has mu-opioid receptor agonist activity, which SSRIs lack.

Q4: Can tianeptine be used during pregnancy or breastfeeding?

A: Tianeptine is generally considered unsafe during pregnancy and breastfeeding due to limited safety data and potential fetal opioid dependence. Safer alternatives are recommended.

Q5: Is tianeptine addictive?

A: Chronic high-dose misuse of tianeptine can lead to dependence and withdrawal symptoms similar to opioid withdrawal.

Q6: What are the signs of tianeptine overdose?

A: Overdose can manifest as drowsiness, confusion, respiratory depression, coma, and potentially death, especially in combination with other CNS depressants.

Q7: What should I do if a patient experiences tianeptine withdrawal?

A: Tianeptine withdrawal can be managed similarly to opioid withdrawal, with supportive care, symptomatic treatment, and close monitoring. Consider consultation with an addiction specialist. Gradual tapering of the dose is recommended.

Q8: Does tianeptine interact with other medications?

A: Yes, tianeptine can interact with MAOIs (contraindicated), CNS depressants, serotonergic drugs, alcohol, grapefruit juice, and St. John’s Wort. Always check for potential drug interactions before prescribing.

Q9: Can tianeptine be used in children?

A: Tianeptine is not recommended for use in patients under 18 years of age.

Q10: What liver function tests are recommended for a patient on tianeptine?

A: Periodic liver function tests, including ALT, AST, and alkaline phosphatase, are recommended to monitor for potential hepatotoxicity, especially in patients with pre-existing liver conditions.