Tianeptine for Depression

No longer recruiting at 3 trial locations

Overseen By Alla Landa, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Jonathan A. Javitch, MD, PhD

Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, Opioids

Disqualifiers: Opioid-use disorder, Bipolar, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of tianeptine in treating depression, specifically for individuals who have tried at least two standard antidepressants without success. Participants will undergo an 8-week treatment with tianeptine, an antidepressant medication taken three times a day. This trial may suit individuals aged 21-60 with major depressive disorder (MDD) without psychotic features who have experienced frequent treatment failures. Participants at the Mount Sinai site will also undergo MRI scans to study brain activity. Additionally, blood samples will be collected for genetic analysis to gain insights into depression's genetic links. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial requires that participants stop taking any current antidepressant, antipsychotic, or mood stabilizer medications. If you are taking one of these medications, you may need to discontinue it under the supervision of your doctor or the study clinician.

What is the safety track record for tianeptine?

Research has shown that tianeptine serves as a prescription drug for depression in some countries, but it lacks approval for medical use in the U.S. Some studies have found that misusing tianeptine can cause serious harm, including severe side effects and even death. This risk increases when used recreationally, as it can mimic the effects of opioids, which are strong, potentially addictive pain-relief drugs.

In countries where tianeptine is prescribed, it is generally safe when used correctly for depression. However, since the FDA has not approved it in the U.S., its safety in American clinical settings remains uncertain.

Prospective trial participants considering tianeptine should consult a healthcare provider about any concerns. Healthcare providers can offer personalized advice and help ensure that any treatment aligns with individual health needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for depression, such as SSRIs and SNRIs, which mainly target serotonin reuptake, Tianeptine works differently by enhancing serotonin uptake. This unique mechanism may offer relief for individuals who don't respond well to traditional antidepressants. Additionally, Tianeptine has been noted for its anxiolytic properties, which can be particularly beneficial for patients with depression and co-occurring anxiety. Researchers are excited about Tianeptine because it offers a novel approach that could potentially provide faster relief with fewer side effects.

What is the effectiveness track record for tianeptine in treating depression?

Studies have shown that tianeptine effectively reduces depression symptoms, whether mild or severe. Research suggests that tianeptine works as well as other common antidepressants like fluoxetine and sertraline. It also helps lessen anxiety often accompanying depression. Tianeptine has proven especially helpful for people who haven't found success with other treatments. Participants in this trial will receive open treatment with Tianeptine (Tianeurax 12.5 mg) three times a day for 8 weeks. ^{6 7 8 9 10}

Who Is on the Research Team?

Alla Landa, PhD

Principal Investigator

New York State Psychiatric Institute

Are You a Good Fit for This Trial?

This trial is for adults aged 21-60 with Major Depressive Disorder who haven't improved after at least two treatments with common antidepressants or other therapies like TMS or ketamine. Participants must be able to consent, follow study procedures, and use contraception if applicable. Exclusions include a history of opioid or severe substance abuse, psychotic disorders, high suicide risk, previous tianeptine treatment, certain medical conditions including severe obesity that affects MRI scanning eligibility.

Inclusion Criteria

I have been diagnosed with Major Depressive Disorder without experiencing psychosis.

If you are a woman who can have a baby, you need to use birth control during the study.

I am between 21 and 60 years old.

Exclusion Criteria

I have been treated with Tianeptine before.

I am currently taking medication for depression, psychosis, or mood stabilization.

I can stop taking certain medications under doctor's advice if needed for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive an 8-week treatment trial of tianeptine, including MRI procedures for MSSM patients

8 weeks

Multiple visits (in-person) for treatment and MRI procedures

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tianeptine Sodium

Trial Overview The trial is testing the effectiveness of Tianeptine Sodium in treating people with Treatment Resistant Depression over an 8-week period. It includes MRI scans for some participants to observe brain changes and genetic tests to find links between genes and depression.

How Is the Trial Designed?

Group I: Open Treatment Experimental Treatment 1 Intervention

All subjects will be treated for 8 weeks of treatment with Tianeptine (Tianeurax 12.5 mg) 3 times a day (9am, 1pm, 5pm).

Who Is Running the Clinical Trial?

Jonathan A. Javitch, MD, PhD

Lead Sponsor

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

Published Research Related to This Trial

Tianeptine is an effective antidepressant that works differently from most antidepressants by increasing serotonin uptake and reducing stress-induced neuronal damage, with a favorable safety profile that includes minimal cognitive and cardiovascular side effects.

It has shown comparable efficacy to traditional antidepressants like amitriptyline and SSRIs, while also being particularly beneficial for patients with anxiety and those with alcohol dependence, making it a promising option for various subgroups of depressed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tianeptine: a review of its use in depressive disorders. Wagstaff, AJ., Ormrod, D., Spencer, CM.[2018]

In a year-long multicenter trial with 380 depressed patients, tianeptine significantly reduced depression scores from day 14 and maintained this improvement for up to 12 months, indicating its efficacy as an antidepressant.

The treatment was well-tolerated, with only 11% of patients withdrawing due to depression recurrence and 2% due to side effects, which were generally mild, suggesting that tianeptine is a safe option for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of tianeptine in 380 depressed patients. Lôo, H., Ganry, H., Dufour, H., et al.[2014]

Tianeptine is a unique antidepressant that not only alleviates depression but also reduces anxiety without causing sedation or impairing memory, making it different from traditional benzodiazepines.

It works by enhancing serotonin uptake and improving hippocampal activity, which may contribute to its effects on memory and stress adaptation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tianeptine, an uncommon psychotropic drug]. Kamoun, A., Labrid, C., Mocaër, E., et al.[2014]

In a study involving 55 patients with recurrent depressive disorder, tianeptine showed high preventive efficacy, with 61% of patients achieving full response and 74% showing overall improvement after 12 months of treatment.

Tianeptine was well tolerated, with only mild side effects reported, indicating it is a safe option for long-term management of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preventive efficacy of tianeptine in recurrent depression with frequent exacerbations]. Mosolov, SN., Vertogradova, OP., Panteleeva, GP., et al.[2016]

Tianeptine is an effective antidepressant that not only shows greater efficacy than placebo but also has similar or superior effects compared to traditional antidepressants like amitriptyline and fluoxetine, particularly in patients with major depression and anxiety.

Tianeptine is well tolerated with fewer side effects compared to amitriptyline, making it a safer option for elderly patients and those recovering from alcohol withdrawal, as it has a lower incidence of common adverse effects like dry mouth and dizziness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression. Wilde, MI., Benfield, P.[2018]

Tianeptine, an antidepressant not approved by the FDA in the U.S., has been identified as an opioid receptor agonist, leading to concerns about its potential for abuse and severe adverse effects, including death.

From 2000 to 2017, calls to poison control centers regarding tianeptine exposures increased, particularly among individuals aged 21-40, with common symptoms resembling opioid toxicity and withdrawal effects, indicating a growing public health risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of Tianeptine Exposures Reported to the National Poison Data System - United States, 2000-2017. El Zahran, T., Schier, J., Glidden, E., et al.[2018]

Tianeptine has been shown to be effective in treating depressive disorders, with 78% of patients responding positively to treatment, as evidenced by both clinical rating scales and patient feedback.

In addition to its antidepressant effects, tianeptine also alleviates anxiety symptoms and somatic complaints, making it a versatile option for patients experiencing a range of depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant and anxiolytic activities of tianeptine: an overview of clinical trials. Defrance, R., Marey, C., Kamoun, A.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2902200/

The neurobiological properties of Tianeptine (Stablon) Tianeptine is effective in reducing symptoms of depression in mild to moderate-to-severe major depression, while it alleviates anxious symptoms associated ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11463130/

Tianeptine: a review of its use in depressive disorders Extended treatment with tianeptine decreases the incidence of relapse/recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032799000099

Efficacy and safety of tianeptine in the treatment ... Tianeptine has been shown to be effective in patients suffering from depression alone or associated with anxiety or alcoholism.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04249596

Tianeptine for Treatment Resistant Depression The major goals of this project are (1) to determine if tianeptine is an effective antidepressant in patients who have failed two previous trials, (2) to define ...

5. psychiatrist.com psychiatrist.com/jcp/tianeptine-in-elderly-mdd-patients/

Efficacy of Tianeptine 25-50 mg in Elderly Patients With ... The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17) total score. Results: Tianeptine improved depressive ...

6. fda.gov fda.gov/consumers/consumer-updates/tianeptine-products-linked-serious-harm-overdoses-death

Tianeptine Products Linked to Serious Harm, Overdoses, ... Tianeptine is not approved by the FDA for any medical use. Some companies are illegally marketing and selling tianeptine products and making ...

7. cdc.gov cdc.gov/mmwr/volumes/67/wr/mm6730a2.htm

Characteristics of Tianeptine Exposures Reported to the ... Several case studies have reported severe adverse effects and even death from recreational abuse of tianeptine (3–5). To characterize tianeptine ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10444703/

Tianeptine, an Antidepressant with Opioid Agonist Effects Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance.

9. mayoclinic.org mayoclinic.org/healthy-lifestyle/consumer-health/in-depth/tianeptine-is-safe-use-possible/art-20562252

Tianeptine: Is safe use possible? However, tianeptine can have ill effects and can even lead to death. Talk to your healthcare professional if you have questions about care for ...

10. webmd.com webmd.com/vitamins/ai/ingredientmono-1587/tianeptine

Tianeptine – Uses, Side Effects, and More Tianeptine is a prescription drug used for depression in some European, Asian, and Latin American countries. It is not approved for use in the US.