Tianeptine for Depression
Recruiting in Palo Alto (17 mi)
+3 other locations
Overseen byBret R Rutherford, MD
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: New York State Psychiatric Institute
Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, Opioids
Disqualifiers: Opioid-use disorder, Bipolar, Psychosis, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests tianeptine, an antidepressant that targets specific brain receptors, on adults with major depressive disorder who haven't responded to other treatments. The goal is to see if tianeptine can help these patients by working on the brain's natural painkiller system. Tianeptine is known for its unique way of working and its ability to protect the brain from stress.
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 evidence supports the effectiveness of the drug Tianeptine for depression?
Research shows that Tianeptine is effective in treating depression and anxiety, with similar effectiveness to other antidepressants like fluoxetine and amitriptyline. It is particularly beneficial for elderly patients and those recovering from alcohol withdrawal, with fewer side effects compared to some other antidepressants.
12345How does the drug Tianeptine differ from other treatments for depression?
Tianeptine is unique because it increases serotonin uptake in the brain, unlike most antidepressants that block serotonin reuptake. It also has fewer sedative and cardiovascular side effects, making it suitable for elderly patients and those with alcohol withdrawal.
12467Eligibility Criteria
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.
+3 more
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.
+14 more
Trial Timeline
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)
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Open TreatmentExperimental Treatment1 Intervention
All subjects will be treated for 8 weeks of treatment with Tianeptine (Tianeurax 12.5 mg) 3 times a day (9am, 1pm, 5pm).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount SinaiNew York, NY
Stanford Depression Research Clinic at Stanford University School of MedicineStanford, CA
1051 Riverside DriveNew York, NY
New York State Psychiatric InstituteNew York, NY
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Who Is Running the Clinical Trial?
New York State Psychiatric InstituteLead Sponsor
Stanford UniversityCollaborator
Icahn School of Medicine at Mount SinaiCollaborator
References
Tianeptine: a review of its use in depressive disorders. [2018]Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for tianeptine but dothiepin appeared superior in another study. Extended treatment with tianeptine decreases the incidence of relapse/recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to tianeptine. The adverse effects associated with tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis.
Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression. [2018]Tianeptine is a novel antidepressant agent, both structurally (modified tricyclic) and in terms of its pharmacodynamic profile. Unlike other antidepressant agents, tianeptine stimulates the uptake of serotonin (5-hydroxytryptamine; 5-HT) in rat brain synaptosomes and rat and human platelets, increases 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebral tissue and plasma, and reduces serotonergic-induced behaviour. Tianeptine reduces the hypothalamic-pituitary-adrenal response to stress, antagonises stress-induced behavioural deficits and prevents changes in cerebral morphology. The antidepressant efficacy of tianeptine, as shown in 2 trials of patients with major depression or depressed bipolar disorder with or without melancholia, is greater than that of placebo. In patients with major depression without melancholia or psychotic features, depressed bipolar disorder or dysthymic disorder, the antidepressant efficacy of short term (4 weeks to 3 months) tianeptine therapy appears to be similar to that of amitriptyline, imipramine and fluoxetine and may be superior to that of maprotiline in patients with coexisting depression and anxiety. However, submaximal dosages of amitriptyline and maprotiline were used in these studies. Preliminary evidence suggests that tianeptine may also be effective in patients with endogenous depression. Progressive therapeutic improvements have been observed with up to 1 year of tianeptine treatment, and long term therapy may reduce the rate of relapse or recurrence. Tianeptine is effective in the treatment of depression in elderly and post-alcohol-withdrawal patient subgroups. Tianeptine was more effective in reducing psychic anxiety than placebo in patients with major depression or depressed bipolar disorder with or without melancholia. The overall anxiolytic properties of tianeptine in patients with coexisting depression and anxiety appear to be similar to those of amitriptyline, imipramine and fluoxetine and may be superior to those of maprotiline, although submaximal dosages of amitriptyline and maprotiline were used. Studies of tianeptine in patients with primary anxiety have not been conducted. Tianeptine is well tolerated in the short (3 months) and long (up to 1 year) term. The incidence of dry mouth (38 vs 20%), constipation (19 vs 15%), dizziness/syncope (23 vs 13%), drowsiness (17 vs 10%) and postural hypotension (8 vs 3%) are greater with amitriptyline than with tianeptine. Insomnia and nightmares occur in more tianeptine than amitriptyline recipients (20 vs 7%). The relative lack of sedative, anticholinergic and cardiovascular adverse effects with tianeptine makes it particularly suitable for use in the elderly and in patients following alcohol withdrawal; these patients are known to have increased sensitivity to the adverse effects associated with psychotropic drugs.(ABSTRACT TRUNCATED AT 400 WORDS)
Characteristics of Tianeptine Exposures Reported to the National Poison Data System - United States, 2000-2017. [2018]Tianeptine (marketed as Coaxil or Stablon) is an atypical tricyclic drug used as an antidepressant in Europe, Asia, and Latin America. In the United States, tianeptine is not approved by the Food and Drug Administration (FDA) for medical use and is an unscheduled pharmaceutical agent* (1). Animal and human studies show that tianeptine is an opioid receptor agonist (2). Several case studies have reported severe adverse effects and even death from recreational abuse of tianeptine (3-5). To characterize tianeptine exposures in the United States, CDC analyzed all exposure calls related to tianeptine reported by poison control centers to the National Poison Data System (NPDS)† during 2000-2017. Tianeptine exposure calls, including those for intentional abuse or misuse, increased across the United States during 2014-2017, suggesting a possible emerging public health risk. Most tianeptine exposures occurred among persons aged 21-40 years and resulted in moderate outcomes. Neurologic, cardiovascular, and gastrointestinal signs and symptoms were the most commonly reported health effects, with some effects mimicking opioid toxicity. A substantial number of tianeptine exposure calls also reported clinical effects of withdrawal. Among 83 tianeptine exposures with noted coexposures, the most commonly reported coexposures were to phenibut, ethanol, benzodiazepines, and opioids.
Antidepressant and anxiolytic activities of tianeptine: an overview of clinical trials. [2014]Tianeptine is a new antidepressant effective against anxiety accompanying mood disturbances. Its clinical properties have been assessed by double-blind controlled studies (versus imipramine, amitriptyline, nomifensine, viloxazine) in depressed patients fulfilling the diagnostic criteria of the DSM III: single recurrent major depressive episodes without melancholia or psychotic features, and dysthymic disorders. The authors have concluded that tianeptine is effective in depressive disorders as shown both by depression rating scales and subjective impressions of treated patients. This improvement increases regularly with time. Seventy-eight percent of patients were considered to be "responders" at the end of the treatment with tianeptine. Antidepressant activity of tianeptine is equally present in depressive states appearing after withdrawal from alcohol. In depressed patients with anxiety, the results also reveal the efficacy of tianeptine on anxiety symptoms. Tianeptine, in addition, shows a marked action on somatic complaints. These results have been confirmed by open long-term trials, particularly in the elderly. Tianeptine can be placed in a middle position in the bipolar classification, between the sedative and stimulant antidepressants. Its antidepressant and anxiolytic properties and its action on somatic complaints make the drug particularly suitable for the treatment of the entire range of depressive symptomatology.
[Tianeptine, an uncommon psychotropic drug]. [2014]The pharmacological studies show that tianeptine (Stablon) is an original psychotropic drug. In classical and behavioural pharmacology, tianeptine has a novel antidepressant profile, different from other molecules and an anxiolytic effect but different from the benzodiazepines. Tianeptine does not cause sedation and sleeping troubles. In mice, tianeptine does not impair spatial memory but have facilitating effects on both working and reference memory. Tianeptine also increased the focalization of attention in cat and is active on comportmental adaptation models in stress. The electrophysiological data showed that tianeptine increases activity of the hippocampus pyramidal cells and decreases the recovery time after inhibitory substances application. Neurobiochemical studies showed that tianeptine increases serotonin uptake, in rat brain and in rat and human platelets, after acute and chronic treatment. Neuroendocrinology data showed that tianeptine decreases CRF and ACTH levels. Current research on the effect of tianeptine on acetylcholine could explain its anti-stress and memory facilitation activity.
Long-term use of tianeptine in 380 depressed patients. [2014]Tianeptine is a new tricyclic compound whose principal action is to increase the reuptake of serotonin. In a multicentre trial in which 380 depressed patients were treated for one year, tianeptine produced a significant reduction in the MADRS scores from day 14, with a sustained reduction maintained for up to 12 months; other measures of efficacy (HRSA, HSCL, and CGI) also reflected the improvement. Only 11% of patients withdrew because of recurrence of depression and 2% because of side-effects, which were mainly drowsiness, irritability, and gastrointestinal disturbance. Apart from a minor reduction in heart rate, unaccompanied by any conduction changes, no clinically relevant changes in vital signs or laboratory tests were seen. Seven subjects who attempted suicide by tianeptine overdose had favourable outcomes, in spite of also taking other psychotropic drugs or alcohol. No evidence of tolerance or withdrawal symptoms was seen after treatment was stopped. These results suggest that tianeptine has the potential to provide safe antidepressant activity in both the acute and chronic phases of treatment.
[Preventive efficacy of tianeptine in recurrent depression with frequent exacerbations]. [2016]The results of the studies of 4 Russian research centers are summarized. Tianeptine (coaxil) was used in the treatment of 55 patients with ICD-10 diagnosis of recurrent depressive disorder (F32.1), 50 patients have completely finished the treatment. Tianeptine was assigned in dosage of 12.5 mg 3 times daily (patients over 65 years old received 25.0 mg daily) during 12 months. The drug was shown to have a high preventive efficacy for the disorder. Sixty-one percent of patients were full-responders. Taken together with partial responders (13%), an improvement was observed in 74% patients. The drug demonstrated a well tolerability with a rare and mild expression of side-effects.