What side effects are associated with this type of intervention?

Common treatments for depression, such as esketamine and ketamine (NMDA receptor antagonists), can cause side effects including dissociation, dizziness, nausea, increased blood pressure, and cognitive impairment. Other widely used antidepressants like SSRIs and SNRIs may lead to gastrointestinal issues, sexual dysfunction, weight gain, and sleep disturbances. It is important to discuss these potential side effects with a healthcare provider to determine the most appropriate treatment.

What prior FDA approvals exist?

Esketamine nasal spray, an NMDA receptor antagonist, is one of the more recent FDA-approved treatments for treatment-resistant depression. This class of drugs works differently from traditional antidepressants like SSRIs and SNRIs by targeting the glutamatergic system. Another notable NMDA receptor antagonist is ketamine, which has been used off-label for depression and has shown rapid antidepressant effects. These treatments are particularly considered for patients who have not responded to other forms of antidepressant therapy.

What other types of research exist?

Promising novel alternatives to Esketamine Nasal Spray for depression treatment in 2024 include: 1) Psilocybin-assisted therapy, which has shown rapid and sustained symptom reduction in clinical trials. 2) Intranasal ketamine, which has been explored for its efficacy in treatment-resistant depression. 3) SSRIs/SNRIs like paroxetine, which have been effective in various depressive disorders. 4) Adjunctive treatments like varenicline for patients with comorbid conditions such as smoking. These alternatives offer different mechanisms of action and therapeutic benefits, providing options for personalized treatment plans.

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NMDA receptor antagonist

Esketamine Nasal Spray for Depression

Phase 4

Waitlist Available

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

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

Must have

Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for single-episode MDD or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the MINI. Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age

Participant must have had nonresponse (<=25% improvement) to >=2 oral antidepressant treatments in the current episode of depression, assessed using the MGH-ATRQ, and confirmed by documented records (example, medical/pharmacy/prescription records or a letter from a treating physician)

Must not have

The participant has used ketamine/esketamine (lifetime)

The participant's depressive symptoms have previously demonstrated nonresponse to an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to day 28

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial is testing a nasal spray called esketamine to see if it helps people with depression who haven't improved with other treatments. The spray is given in two different doses. Esketamine works by balancing brain chemicals to improve mood and reduce depressive symptoms. Esketamine nasal spray has been shown in previous studies to rapidly reduce depressive symptoms, including in patients with treatment-resistant depression.

Who is the study for?

Adults with treatment-resistant depression, who haven't responded to at least two oral antidepressants in their current episode, can join this trial. They must be medically stable and able to self-administer nasal spray medication. People over 65 should have had their first depression onset before age 55. Those with significant medical conditions or a history of seizures are excluded.

What is being tested?

The study is testing esketamine nasal spray doses (56 mg and 84 mg) against a placebo to see if they improve symptoms of depression after four weeks. Participants' depressive symptoms will be measured using the MADRS scale from the start until Day 28.

What are the potential side effects?

Esketamine may cause side effects such as dissociation, dizziness, nausea, sedation, increased blood pressure, anxiety, lack of energy, vomiting and feeling drunk.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with depression without psychosis, first occurred before I was 55.

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I have tried at least two antidepressants without much improvement.

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I can use a nasal spray by myself and follow the instructions.

Exclusion Criteria

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

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I have used ketamine or esketamine at some point in my life.

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My depression didn't improve after 7 or more ECT treatments.

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I have had VNS or DBS for my current depression episode.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to day 28

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to day 28

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to day 28 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 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from Day 1 (Pre-randomization) to the End of the 4-week Double-Blind Treatment Phase (Day 28)

Secondary study objectives

Change from Baseline in MADRS Total Score from Day 1 (Pre-randomization) to Day 2

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Group I: PlaceboExperimental Treatment1 Intervention

Participants will receive nasal spray treatment with placebo twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 MADRS assessment).

Group II: Esketamine 84 mgExperimental Treatment1 Intervention

Participants will receive nasal spray treatment with esketamine 84 mg twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 MADRS assessment).

Group III: Esketamine 56 Milligram (mg)Experimental Treatment1 Intervention

Participants will receive nasal spray treatment with esketamine 56 mg twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 Montgomery-Asberg Depression Rating Scale \[MADRS\] assessment).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Esketamine 56 mg

2020

Completed Phase 4

~1520

Esketamine 84 mg

2020

Completed Phase 4

~1570

Placebo

1995

Completed Phase 3

~2670

0 / 6Eligibility 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

Esketamine, an NMDA receptor antagonist, works by modulating glutamate activity in the brain, which can lead to rapid antidepressant effects. This is particularly important for treatment-resistant depression, where traditional antidepressants may fail. Other common treatments include SSRIs and SNRIs, which increase serotonin and norepinephrine levels, respectively, to improve mood and emotional regulation. Tricyclic antidepressants also increase these neurotransmitters but have a broader mechanism of action. Understanding these mechanisms helps patients and clinicians choose the most effective treatment, especially when rapid symptom relief is needed or when other treatments have failed.

Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials.Consistently Modest Antidepressant Effects in Clinical Trials: the Role of Regulatory Requirements.