Using Tianeptine to Treat Depression That Doesn't Respond to Other Medications

Tianeptine for Treatment Resistant Depression

Phase 4 Interventional New York State Psychiatric Institute · NCT04249596

This study is testing if a medication called tianeptine can help adults with depression that hasn't improved with other treatments.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment75 (estimated)
Ages21 Years to 60 Years
SexAll
SponsorNew York State Psychiatric Institute Academic / other
Locations3 sites (Stanford, California and 2 other locations)
Trial IDNCT04249596 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy of tianeptine, an atypical antidepressant, in patients with treatment-resistant depression (TRD). Conducted at multiple prestigious institutions, the study will recruit 75 participants aged 21-60 who have not responded to at least two previous antidepressant treatments. The trial will focus on a subgroup of patients with deficient opioid receptor signaling, hypothesizing that they may respond better to tianeptine. Participants will undergo an 8-week treatment period, with oversight from experienced investigators at each site.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21-60 with a diagnosis of major depressive disorder who have failed at least two previous antidepressant treatments.

Not a fit: Patients with a history of opioid-use disorder or current substance-use disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients suffering from treatment-resistant depression.

How similar studies have performed: While tianeptine has been used successfully in other countries, this specific approach targeting opioid receptor signaling in TRD is novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Age 21 - 60 years, male or female
2. Current diagnosis of Major Depressive Disorder (MDD) without psychotic features
3. 24-item Hamilton Rating Scale for Depression (HRSD) ≥ 16
4. At least two previous antidepressant treatment failures (adequate trials within current episode) with a SSRI, SNRI, bupropion, tricyclic antidepressant, mirtazapine, nefazodone, or monoamine oxidase inhibitor, or transcranial magnetic stimulation (TMS), or IV ketamine or nasal ketamine.
5. Capable of providing informed consent and complying with study procedures
6. Currently using or willing to use contraception, if woman of childbearing potential (such as condoms, IUD, or oral contraceptive), for duration of the study.

Exclusion Criteria:

1. Any history of opioid-use disorder
2. Any history of moderate- non-opioid (except for Nicotine) substance-use disorder.
3. Any severity of alcohol use disorder (including mild)
4. Past or current psychosis, psychotic disorder (including psychotic MDD), mania, or bipolar disorder
5. Hamilton Rating Scale for Depression (HRSD) suicide item \> 2 or Clinical Global Impressions (CGI)-Severity score of 7 at baseline
6. Previous or current treatment with Tianeptine
7. Current treatment or currently taking an opioid.
8. Failed depression treatment with electroconvulsive therapy.
9. Acute, severe, or unstable medical illness
10. Weight \> 300 lbs, or girth size incompatible with scanner bore.
11. Any physical or intellectual disability adversely affecting ability to complete assessments. MMSE \<26
12. for MSSM site - Having contraindication to MRI scanning (such as metal in body) or inability to tolerate the scanning procedures (e.g., severe obesity, claustrophobia)
13. Current pregnancy or currently breast feeding.
14. Abnormal baseline liver function tests
15. Currently being treated with an antidepressant medication, an antipsychotic or mood stabilizer.

    a) If a participant is taking a protocol dis-allowed medication at the time of screening and despite medication treatment still meets the inclusion criteria of an HRSD\>16, the participant may discontinue the medication under the supervision of their treating physician or the study clinician.
16. Positive urine toxicity at screening (except for cannabinoid)

Where this trial is running

Stanford, California and 2 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Treatment Resistant Depression
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.