Ketamine for Bipolar Depression and Suicidal Thoughts

(SevereBD Trial)

Recruiting at 1 trial location

Overseen By Martin Brecher, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NeuroRx, Inc.

Must not be taking: Antidepressants, Mood stabilizers

Disqualifiers: Substance use disorder, Schizophrenia, Hypertension, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 24 hours

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment that starts with a ketamine injection to quickly reduce severe depression and suicidal thoughts, followed by maintenance pills. It targets patients with severe bipolar depression who need rapid symptom relief. Ketamine rapidly alters brain activity, and the pills help maintain these positive changes. Ketamine has shown effectiveness as a rapid-acting antidepressant with antisuicidal effects, but evidence for long-term maintenance therapy is limited.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it allows for stable concurrent psychotherapy and hypnotic therapy if they have been stable for a certain period. However, you cannot be on more than one approved antidepressant or mood stabilizer at randomization.

Is ketamine safe for treating bipolar depression and suicidal thoughts?

Ketamine is generally considered safe at low single doses for treating depression, but there are concerns about its safety with repeated use or higher doses. Some side effects include dissociative symptoms (feeling disconnected from reality), high blood pressure, and confusion, which are usually short-lived. Long-term safety data is limited, and there is a potential risk of abuse or dependence. ^{1 2 3 4 5}

How is the drug NRX100 (ketamine) unique for treating bipolar depression and suicidal thoughts?

NRX100 (ketamine) is unique because it can rapidly reduce depressive symptoms and suicidal thoughts, often within hours, by blocking NMDA receptors in the brain, which is different from traditional antidepressants that can take weeks to work. ^{6 7 8 9 10}

What evidence supports the effectiveness of the drug NRX100 for treating bipolar depression and suicidal thoughts?

Research shows that ketamine, a component of NRX100, can quickly reduce suicidal thoughts and depressive symptoms in people with treatment-resistant depression and bipolar disorder. It has been found to have a rapid antidepressant effect, with benefits seen within 24 hours and lasting for 1-2 weeks after treatment. ^{2 6 7 9 11}

Who Is on the Research Team?

Martin Brecher, MD

Principal Investigator

VP, Clinical Development, NeuroRx, Inc.

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with severe bipolar depression and recent suicidal thoughts or behaviors. Participants must understand the study, be likely to follow its rules, have a stable living situation, and use effective birth control if applicable. They can't join if they're pregnant or don't meet health requirements.

Inclusion Criteria

The subject had a negative urinary pregnancy test at both the screening and randomization visits, confirming that she was not pregnant.

The individual resides in a stable living situation and has an identified reliable informant who agrees that the individual has bipolar disorder

Not able to have children (e.g., physically incapable of becoming pregnant, permanently sterilized, or post-menopausal); using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or not sexually active.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single IV infusion of NRX-100 (ketamine) or placebo for rapid stabilization of symptoms

24 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Weekly visits (in-person)

Extension

Participants who respond successfully to treatment are offered enrollment in a six-week follow-up study of NRX-101 vs. standard of care

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NRX100
• Placebo

Trial Overview The trial tests NRX-100 (ketamine HCL) against a placebo for quick relief of depression and suicidal thoughts in bipolar disorder patients. It aims to see if NRX-100 works better than a placebo within 24 hours after taking it.

How Is the Trial Designed?

Group I: Saline (placebo) infusion Experimental Treatment 1 Intervention

Infusion of IV Saline

Group II: NRX-100 infusion Experimental Treatment 1 Intervention

Infusion of IV NRX-100 (ketamine)

Who Is Running the Clinical Trial?

NeuroRx, Inc.

Lead Sponsor

Trials

14

Recruited

1,600+

Target Health Inc.

Industry Sponsor

Trials

7

Recruited

520+

Published Research Related to This Trial

In a study of 156 suicidal patients, ketamine infusions significantly reduced suicidal ideation, with early remission at day 1 and day 3 being strong predictors of sustained remission at week 6.

Clinical factors like bipolar disorder and lower initial suicidal thoughts were linked to early remission, but overall, no specific clinical factors reliably predicted long-term outcomes, highlighting the need for ongoing monitoring and comprehensive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical predictive factors and trajectories of suicidal remission over 6 weeks following intravenous ketamine for suicidal ideation. Jollant, F., Demattei, C., Fabbro, P., et al.[2023]

In a study of 201 adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD), intravenous (IV) ketamine significantly reduced symptoms of anxiety, irritability, and agitation in those with mixed features, indicating its effectiveness in treating these symptoms.

Participants with anxiety, irritability, and agitation (AIA) experienced greater reductions in overall depressive symptoms and suicidal ideation compared to those without AIA, suggesting that IV ketamine could be a rapid treatment option for adults with mood disorders presenting with mixed features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. McIntyre, RS., Lipsitz, O., Rodrigues, NB., et al.[2021]

Ketamine has been shown to provide rapid antidepressant effects within 24 hours, making it a potential option for patients with treatment-resistant depression, although its long-term efficacy remains unclear.

The safety profile of low doses of ketamine is generally good, but there is insufficient data on the effects of repeated higher doses, highlighting the need for further research on its long-term use in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and depression: a narrative review. Corriger, A., Pickering, G.[2020]

Ketamine is a rapid-acting antidepressant that can show effects within hours and sustain relief from Major Depressive Disorder (MDD) symptoms for up to 7 days, representing a significant advancement for treatment-resistant depression.

The chapter discusses ketamine's safety and efficacy, including its potential to reduce suicidal thoughts and its interaction with psychotherapy, highlighting its role as a novel therapeutic option for individuals who do not respond to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Major Depressive Disorder. Costi, S.[2023]

In a study involving 16 recent suicide attempters, a single intravenous dose of ketamine (0.5 mg/kg) led to rapid and significant reductions in suicidal thoughts within 24 hours, with effects lasting up to 6 months post-infusion.

The results indicate that ketamine is a safe and effective treatment for reducing suicidality in high-risk patients, suggesting it could be integrated into existing healthcare settings for those in acute psychiatric care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Ketamine Infusion after Suicide Attempt: New Frontiers in Treating Acute Suicidality in a Real-World Medical Setting. Shivanekar, S., Gopalan, P., Pizon, A., et al.[2023]

Citations

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

Clinical predictive factors and trajectories of suicidal remission over 6 weeks following intravenous ketamine for suicidal ideation. [2023]

2. Denmark pubmed.ncbi.nlm.nih.gov

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ketamine and depression: a narrative review. [2020]

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

Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. [2022]

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

Clinical predictors of ketamine response in treatment-resistant major depression. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Dissociable effects of the noncompetitive NMDA receptor antagonists ketamine and MK-801 on intracranial self-stimulation in rats. [2021]

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

Safety and effectiveness of NMDA receptor antagonists for depression: A multidisciplinary review. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Ketamine for Major Depressive Disorder. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Ketamine treatment for depression: a review. [2023]

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

Ketamine and esketamine for crisis management in patients with depression: Why, whom, and how? [2022]

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

A Pilot Study of Ketamine Infusion after Suicide Attempt: New Frontiers in Treating Acute Suicidality in a Real-World Medical Setting. [2023]