TS-161 for Treatment-Resistant Depression

Overseen By Carlos A Zarate, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: MAOIs, Clozapine, Fluoxetine, others

Disqualifiers: Schizophrenia, Substance abuse, Personality disorder, 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

Compensation: Varies

Number of Visits: 1

Duration: 8-9 weeks

11 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current psychiatric medications. There will be a tapering-off period followed by a 2-week drug-free period before starting the trial medication.

What data supports the effectiveness of the drug TS-161 for treatment-resistant depression?

The research highlights that atypical antipsychotics, which are similar to TS-161, have been approved for use in treatment-resistant depression and have shown benefits, although they come with potential side effects. This suggests that TS-161 might also be effective, as it could share similar properties with these approved treatments. ^{1 2 3 4 5}

What safety data exists for TS-161 (Esketamine) in humans?

Esketamine, used for treatment-resistant depression, has been studied for safety in both nasal spray and intravenous forms. Patients reported satisfaction with the treatment, and adverse events were consistent with its known safety profile, indicating it is generally safe for human use. ^{4 6 7 8 9}

How is the drug TS-161 different from other treatments for treatment-resistant depression?

TS-161 may be similar to esketamine, a fast-acting nasal spray that works differently from traditional antidepressants by targeting NMDA receptors in the brain, offering a novel approach for those who haven't responded to other treatments. ^{1 4 6 10 11}

What is the purpose of this trial?

This trial tests TS-161, a new drug for adults aged 18-65 with treatment-resistant depression. TS-161 aims to improve mood by changing how brain cells communicate, without the severe side effects of similar drugs.

Research Team

Carlos A Zarate, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Eligibility Criteria

Adults aged 18-65 with major depressive disorder (MDD) who haven't improved after trying at least one antidepressant can join. They must understand the study, consent to it, be willing to stay in a hospital for tests, and avoid alcohol and drugs. Women must use contraception; men must use birth control during the study.

Inclusion Criteria

For females of reproductive potential: use of contraception while in the study and for an additional 4 weeks after stopping the study drug

I have tried at least one antidepressant without success.

I have been diagnosed with major depressive disorder.

Exclusion Criteria

Pregnant participants or those planning to become pregnant in the next 12 to 16 weeks while in the study, or those who are breastfeeding

You have strong thoughts of hurting yourself or someone else.

I do not have any major illnesses like heart or kidney disease that would make joining a study unsafe.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Tapering and Drug-Free Period

Participants are tapered off their psychiatric medicines and have a 2-week drug-free period

2 weeks

Inpatient visit at NIH

Treatment

Participants receive TS-161 or placebo for 3 weeks, followed by a 2-3 week drug-free period, then crossover to the alternate treatment for another 3 weeks

8-9 weeks

Multiple visits for interviews, physical exams, psychological tests, MRI, MEG, and ECGs

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• TS-161

Trial Overview The trial is testing TS-161's effectiveness on MDD symptoms compared to a placebo. Participants will stop their current meds, have a drug-free period, then take either TS-161 or placebo for three weeks each with breaks in between. Tests include interviews, physical exams, brain scans (MRI), mood/thinking tasks, and heart monitoring.

Participant Groups

Group I: TS-161, then Placebo Experimental Treatment 2 Interventions

Participants with major depressive disorder (MDD) were randomized to receive TS-161 100mg capsule orally once per day for three weeks (with option to decrease to 50 mg due to drug intolerance), followed by Placebo capsule orally once per day for three weeks.

Group II: Placebo, then TS-161 Experimental Treatment 2 Interventions

Participants with major depressive disorder (MDD) were randomized to receive Placebo capsule orally once per day for three weeks, followed by TS-161 100mg capsule orally once per day for three weeks (with option to decrease to 50 mg due to drug intolerance).

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Taisho Pharmaceutical Co., Ltd.

Industry Sponsor

Trials

40

Recruited

5,300+

Findings from Research

Esketamine nasal spray is a fast-acting treatment option for patients with treatment-resistant depression (TRD), providing a new avenue for those who have not responded to other therapies.

The expert consensus developed in this study offers practical recommendations for clinicians on how to effectively use esketamine nasal spray, addressing pre-treatment considerations and guidelines for administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical recommendations for the management of treatment-resistant depression with esketamine nasal spray therapy: Basic science, evidence-based knowledge and expert guidance. Kasper, S., Cubała, WJ., Fagiolini, A., et al.[2021]

In a study of 23 adults with treatment-resistant depression, 91.8% reported significant improvements in emotional and daily functioning after using esketamine nasal spray (ESK) alongside an oral antidepressant (OAD).

Patients noted key benefits of ESK treatment, including its effectiveness, rapid onset of action, and a side-effect profile consistent with existing safety data, leading to high satisfaction rates (100% reported satisfaction).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study. Starr, HL., Abell, J., Larish, A., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world evidence from a European cohort study of patients with treatment resistant depression: Baseline patient characteristics. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for Treatment-Resistant Depression: Antidepressants and Atypical Antipsychotics. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

What are the comparative benefits and harms of augmentation treatments in major depression? [2018]

6. England pubmed.ncbi.nlm.nih.gov

Practical recommendations for the management of treatment-resistant depression with esketamine nasal spray therapy: Basic science, evidence-based knowledge and expert guidance. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2). [2020]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Subtypes of treatment-resistant depression determined by a latent class analysis in a Chinese clinical population. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Possible Use of Minocycline in Adjunction to Intranasal Esketamine for the Management of Difficult to Treat Depression following Extensive Pharmacogenomic Testing: Two Case Reports. [2022]