What side effects are associated with this type of intervention?

Common treatments for depression, including NMDA receptor antagonists like esketamine, can cause dizziness, dissociation, headache, nausea, and somnolence. Norepinephrine-dopamine reuptake inhibitors (NDRIs) such as bupropion may lead to insomnia, dry mouth, headache, and an increased risk of seizures. Sigma-1 receptor agonists, though less commonly discussed, may share similar side effects with other antidepressants. Broadly, SSRIs and SNRIs, often used as first-line treatments, can cause gastrointestinal disturbances, sexual dysfunction, weight changes, and increased anxiety initially. All antidepressants should be used cautiously in patients with CNS diseases due to the potential for lowering the seizure threshold.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of depression that share mechanisms with AXS-05. Esketamine, an NMDA receptor antagonist, is approved for treatment-resistant depression. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is another FDA-approved medication for depression. While there are fewer approvals specifically for sigma-1 receptor agonists in depression, fluvoxamine, an SSRI, also acts on sigma-1 receptors and is approved for depression. These approvals highlight the diverse mechanisms targeted in the pharmacotherapy of depression.

What other types of research exist?

Promising novel alternatives to AXS-05 for depression treatment in 2024 include: 1) Esketamine (NMDA receptor antagonist) - an intranasal spray approved for treatment-resistant depression. 2) Psilocybin (serotonin receptor agonist) - showing potential in clinical trials for major depressive disorder. 3) Brexanolone (GABA-A receptor modulator) - approved for postpartum depression, with ongoing research for broader applications. 4) Vortioxetine (serotonin modulator and stimulator) - offering a unique mechanism by targeting multiple serotonin receptors. These alternatives provide diverse mechanisms of action, potentially benefiting patients who do not respond to traditional treatments.

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Other

AXS-05 for Depression

Q: What is the mechanism of action of this treatment?

Common treatments for depression include SSRIs, SNRIs, and newer agents like AXS-05. SSRIs (Selective Serotonin Reuptake Inhibitors) increase serotonin levels in the brain by inhibiting its reuptake, which helps improve mood and emotional stability. SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors) work similarly but also increase norepinephrine levels, providing additional benefits for energy and alertness. AXS-05, a newer treatment, combines dextromethorphan and bupropion, acting as an NMDA receptor antagonist, sigma-1 receptor agonist, and norepinephrine-dopamine reuptake inhibitor. This combination targets multiple pathways involved in mood regulation, potentially offering more comprehensive symptom relief. Understanding these mechanisms helps patients and clinicians choose the most appropriate treatment based on individual symptoms and treatment response.

Phase 4

Recruiting

Research Sponsored by Axsome Therapeutics, Inc.

Eligibility Criteria Checklist

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

Must have

Current major depressive episode of at least 4 weeks in duration

Currently meets DSM-5 criteria for diagnosis of MDD without psychotic features

Must not have

Received any investigational drug or device treatment within 30 days of (Screening) Visit 1, or has been prescribed Auvelity

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial is testing AXS-05, a new medication, to see if it can prevent depression from returning in people who have already improved with it. The study focuses on those with major depressive disorder and aims to maintain their balanced brain chemicals to keep them feeling better. AXS-05 (a combination of dextromethorphan and bupropion) has shown positive results in previous trials for major depressive disorder.

Who is the study for?

This trial is for individuals currently diagnosed with Major Depressive Disorder (MDD) without psychotic features, experiencing a depressive episode lasting at least 4 weeks. It's not open to those who've been in AXS-05 studies before, used investigational drugs or Auvelity within the last month, or can't follow study procedures.

What is being tested?

The study tests if AXS-05 is better than Bupropion at preventing relapse of depression in people whose symptoms improved after taking AXS-05. Participants are randomly assigned to either drug and won't know which one they're getting during the trial.

What are the potential side effects?

Potential side effects for both AXS-05 and Bupropion may include nausea, headache, dry mouth, dizziness, insomnia or anxiety. The exact side effects will vary between individuals.

Eligibility Criteria

Inclusion Criteria

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

Select...

I have been experiencing a major depressive episode for at least 4 weeks.

Select...

I have been diagnosed with major depression without experiencing psychosis.

Exclusion Criteria

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

Select...

I haven't taken any experimental drugs or used experimental devices in the last 30 days, nor have I been prescribed Auvelity.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2019 Phase 3 trial • 327 Patients • NCT04019704

29%

All Others, occurring in <5% of Subjects

16%

Dizziness

13%

Nausea

Headache

Diarrhea

Somnolence

Dry mouth

Pancreatitis

100%

80%

60%

40%

20%

Study treatment Arm

AXS-05

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

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

2Treatment groups

Experimental Treatment

Active Control

Group I: AXS-05Experimental Treatment1 Intervention

AXS-05 tablets, taken twice daily

Group II: BupropionActive Control1 Intervention

Bupropion tablets, taken twice daily

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AXS-05

2018

Completed Phase 3

~1390

0 / 3Eligibility 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 SSRIs, SNRIs, and newer agents like AXS-05. SSRIs (Selective Serotonin Reuptake Inhibitors) increase serotonin levels in the brain by inhibiting its reuptake, which helps improve mood and emotional stability. SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors) work similarly but also increase norepinephrine levels, providing additional benefits for energy and alertness. AXS-05, a newer treatment, combines dextromethorphan and bupropion, acting as an NMDA receptor antagonist, sigma-1 receptor agonist, and norepinephrine-dopamine reuptake inhibitor. This combination targets multiple pathways involved in mood regulation, potentially offering more comprehensive symptom relief. Understanding these mechanisms helps patients and clinicians choose the most appropriate treatment based on individual symptoms and treatment response.

Consistently Modest Antidepressant Effects in Clinical Trials: the Role of Regulatory Requirements.Strategies to achieve clinical effectiveness: refining existing therapies and pursuing emerging targets.