What side effects are associated with this type of intervention?

Common treatments for depression, such as SSRIs (e.g., sertraline, paroxetine) and SNRIs (e.g., duloxetine), often have side effects including nausea, headache, sexual dysfunction, insomnia, and weight gain. Second-generation antidepressants like fluoxetine and escitalopram can also cause similar adverse effects. Additionally, some patients may experience increased anxiety or agitation, particularly at the beginning of treatment. It's important to monitor for these side effects and adjust treatment as necessary under the guidance of a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several classes of antidepressants for the treatment of depression, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine, and atypical antidepressants like bupropion and mirtazapine. More recently, the FDA approved esketamine, a rapid-acting nasal spray for treatment-resistant depression, which represents a significant advancement in rapid-acting antidepressant therapies. This aligns with the potential rapid-acting effects being studied in the trial for TS-161.

What other types of research exist?

Promising novel alternatives to TS-161 for depression treatment include (-)-OSU6162, which has shown efficacy in improving symptoms in patients on antidepressant therapy, and LY2216684, a selective norepinephrine reuptake inhibitor with potential antidepressant effects. Additionally, psilocybin-assisted psychotherapy has shown sustained reductions in depressive symptoms in treatment-resistant depression.

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Antidepressant

TS-161 for Treatment-Resistant Depression

Phase 2

Waitlist Available

Led By Carlos A Zarate, M.D.

Research Sponsored by National Institute of Mental Health (NIMH)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must not have responded to at least one antidepressant

Have major depressive disorder.

Must not have

Participants who had a head injury that caused a loss of consciousness for more than 5 minutes (for the brain imaging)

Participants unwilling to stop undergoing one-on-one psychotherapy for the duration of the study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, 230 min post-drug, and days 1, 2, 3, 7, 14, and 21, per test session.

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects of TS-161 are not detailed here but may include typical antidepressant side effects such as nausea, headaches, sleep disturbances or changes in appetite. The trial includes close monitoring including blood tests and MRIs to ensure participant safety.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have tried at least one antidepressant without success.

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I have been diagnosed with major depressive disorder.

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I have been diagnosed with major depressive disorder.

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I have tried an antidepressant that didn't work for me.

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I have been feeling depressed for at least 4 weeks.

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I am between 18 and 65 years old.

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I can take pills by mouth.

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I have been feeling depressed for at least 4 weeks.

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I am between 18 and 65 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I had a head injury that made me unconscious for over 5 minutes.

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I am willing to pause my one-on-one psychotherapy during the study.

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I have used ketamine or esketamine for depression without improvement.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, 230 min post-drug, and days 1, 2, 3, 7, 14, and 21, per test session.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, 230 min post-drug, and days 1, 2, 3, 7, 14, and 21, per test session.

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, 230 min post-drug, and days 1, 2, 3, 7, 14, and 21, per test session. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from baseline on Montgomery-Asberg Depression Rating Scale (MADRS) total scores

Secondary study objectives

Change from baseline on MADRS total scores

Change from baseline on item 10 (suicidality) of the MADRS and total score on the C-SSRS, and the Scale for Suicidal Ideation (SSI).

Change from baseline on the HDRS, HAM-A, the PANAS, Snaith Hamilton Pleasure Scale (SHAPS), and the Temporal Experience of Pleasure Scale (TEPS) scales.

+6 more

Trial Design

2Treatment groups

Experimental Treatment

Group I: 2Experimental Treatment2 Interventions

Individuals in Arm 2 will receive daily double-blinded placebo for three weeks during Test Session 1 and daily double-blinded TS-161 for three weeks during Test Session 2.

Group II: 1Experimental Treatment2 Interventions

Individuals in Arm 1 will receive daily double-blinded TS-161 for three weeks during Test Session 1 and daily double-blinded placebo for three weeks during Test Session 2.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

TS-161 (50 - 100 mg)

2021

Completed Phase 2

~20

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for depression include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). These medications primarily work by increasing the levels of neurotransmitters such as serotonin, norepinephrine, and dopamine in the brain, which are often imbalanced in depression. SSRIs and SNRIs prevent the reabsorption (reuptake) of serotonin and norepinephrine, respectively, making more of these chemicals available to improve mood. TCAs block the reuptake of both serotonin and norepinephrine, while MAOIs inhibit the enzyme monoamine oxidase, which breaks down neurotransmitters. The potential rapid-acting antidepressant TS-161, being studied for treatment-resistant depression, may offer quicker symptom relief compared to traditional antidepressants, which typically take weeks to show effects. This rapid action is crucial for patients needing immediate relief from severe depressive symptoms.