Tianeptine for Treatment Resistant Depression

NCT04249596 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 7944/8436
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

Brief Summary

The studies will be conducted in parallel at two sites: the the Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount Sinai (MSSM), and Stanford Depression Research Clinic at Stanford University School of Medicine (SUSM). In addition, MRI studies for the MSSM patients will be carried out at the New York State Psychaitric Institute (NYSPI). The following procedures will be approved by the local Institutional Review Boards (IRBs) at each site, where the site PIs (Alla Landa, PhD, NYSPI, James Murrough, MD at MSSM, and Alan Schatzberg, MD at SUSM) will be responsible for overseeing conduct of the study at their respective site. Dr. Jonathan Javitch is the scientific leader of this program and holds the IND for tianeptine use in this study. Investigators will recruit 75 participants with current unipolar MDD, non-delusional, between 21-60, who have failed at least 2 two adequate treatment trials with a standard antidepressant. Patients will receive an 8-week treatment trial of tianeptine. MSSM patients will also undergo structural and task-based magnetic resonance imaging (MRI) that will be performed under Dr. Landa's direction at NYSPI in order to maintain the internal validity of the data set. MSSM subjects will be transported to NYSPI to complete neuroimaging procedures as described below. Participants will be screened for MRI clearance during their screening visit and again at NYSPI on the day of the scan. Subjects will be asked MRI screening questions to ensure that are scanning eligible. Participants will also have additional tubes of blood drawn for human whole-genomic testing. This microarray will be used to identify regions of the human genome that contribute to disease susceptibility and phenotypes. The Illumina human whole-genome array will be used to provide a comprehensive view of the genome, detects single nucleotide polymorphisms and other variations across the genome.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Hamilton Rating Scale for Depression, 24-item (HAMD-24)

  Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

  8 weeks

Secondary Outcomes (2)

• Response Rate

  8 weeks

• Remission Rate

  8 weeks

Study Arms (1)

Open Treatment

EXPERIMENTAL

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

Drug: Tianeptine Sodium

Interventions

Tianeptine Sodium DRUG

At baseline, and following 8 weeks of treatment with tianeptine(12.5 mg, 3x daily), participants will be assessed in a number of procedures to evaluate their emotional and physical pain state and pain stimulus response and the relationship of such states/responses to endogenous opioid signaling. To further assess emotional pain, participants will also undergo fMRI while performing a validated social rejection and social acceptance paradigm known to induce endogenous opioid release in control subjects and blunted release in MDD. Examining both rejection and acceptance is important because the MOR system regulates both social distress and social reward in animals and humans, and tianeptine may also act on abnormal MOR-mediated responses to social acceptance in MDD. Likewise, a second fMRI scan will be used to explore physical pain response using an established thermal pain sensitivity task. The protocol at Stanford University will not include pain testing or imaging studies.

Also known as: Tianeurex 12.5 mg

Open Treatment

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 21 - 60 years, male or female
• Current diagnosis of Major Depressive Disorder (MDD) without psychotic features
• item Hamilton Rating Scale for Depression (HRSD) ≥ 16
• 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.
• Capable of providing informed consent and complying with study procedures
• Currently using or willing to use contraception, if woman of childbearing potential (such as condoms, IUD, or oral contraceptive), for duration of the study.

You may not qualify if:

• Any history of opioid-use disorder
• Any history of moderate- non-opioid (except for Nicotine) substance-use disorder.
• Any severity of alcohol use disorder (including mild)
• Past or current psychosis, psychotic disorder (including psychotic MDD), mania, or bipolar disorder
• Hamilton Rating Scale for Depression (HRSD) suicide item \> 2 or Clinical Global Impressions (CGI)-Severity score of 7 at baseline
• Previous or current treatment with Tianeptine
• Current treatment or currently taking an opioid.
• Failed depression treatment with electroconvulsive therapy.
• Acute, severe, or unstable medical illness
• Weight \> 300 lbs, or girth size incompatible with scanner bore.
• Any physical or intellectual disability adversely affecting ability to complete assessments. MMSE \<26
• 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)
• Current pregnancy or currently breast feeding.
• Abnormal baseline liver function tests
• Currently being treated with an antidepressant medication, an antipsychotic or mood stabilizer.

Sponsors & Collaborators

• Jonathan A. Javitch, MD, PhD: lead
• Stanford University: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (3)

Stanford Depression Research Clinic at Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Limitations and Caveats

Study terminated early due to inadequate recruitment (38 of 75 target enrollment). Open-label, single-arm design without placebo control.

Results Point of Contact

• Title: Jonathan A. Javitch, MD, PhD
• Organization: New York State Psychiatric Instittue

jonathan.javitch@nyspi.columbia.edu

646-774-8600

Study Officials

• Alla Landa, PhD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry and of Pharmacology

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: January 31, 2020
• Study Start: October 14, 2020
• Primary Completion: August 27, 2024
• Study Completion: August 27, 2024
• Last Updated: January 23, 2026
• Results First Posted: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)