Ketamine for Bipolar Depression and Suicidal Thoughts

(SevereBD Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment to determine if it can quickly reduce symptoms of severe bipolar depression and suicidal thoughts. It involves an IV infusion of a drug called NRX-100 (ketamine) and compares its effects to a placebo (a substance with no active drug). Individuals diagnosed with bipolar disorder who experience severe depression with suicidal thoughts may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that NRX-100, a type of ketamine administered through an IV, might be a safe option for treating bipolar depression. Studies have found that ketamine can effectively reduce suicidal thoughts in people with bipolar disorder. In six reviewed studies, ketamine proved both effective and relatively safe for this condition.

While the treatment appears promising, some side effects emerged in research. Recipients of ketamine sometimes experienced a temporary mood increase (manic switch) or had suicidal thoughts, though these events were uncommon.

Overall, evidence suggests that NRX-100 is well-tolerated by most patients. It has been tested in various studies and is currently under further investigation to confirm its benefits and safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NRX-100 because it offers a novel approach to treating bipolar depression and suicidal thoughts. Unlike traditional mood stabilizers and antidepressants, which can take weeks to become effective, NRX-100, derived from ketamine, has the potential to produce rapid antidepressant effects, often within hours or days. This fast-acting quality is particularly crucial for individuals experiencing severe depressive episodes or suicidal ideation, offering hope for quicker relief. Additionally, NRX-100 targets the glutamate system in the brain, a different mechanism of action compared to conventional treatments that primarily affect serotonin or norepinephrine pathways.

What evidence suggests that NRX-100 might be an effective treatment for bipolar depression and suicidal thoughts?

Research has shown that ketamine, the main ingredient in NRX-100, can quickly reduce symptoms of depression and suicidal thoughts. One study found that nearly half (48%) of people with bipolar depression who received ketamine experienced a 50% reduction in their depression symptoms. Another study demonstrated that repeated ketamine treatments significantly lowered depression scores over 2–3 weeks. Participants in this trial may receive NRX-100 (ketamine) infusion, known for its rapid relief of suicidal thoughts. It has been compared to other treatments for this purpose. Overall, evidence suggests that ketamine could effectively treat severe bipolar depression and suicidal thoughts. ^{2 4 6 7 8}

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

Able to understand and provide written and dated informed consent prior to screening

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 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 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 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]

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]

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. psychiatrist.com psychiatrist.com/news/nrx-100s-breakthrough-in-suicidality-treatment/

NRX-100's Breakthrough in Suicidality Treatment NRX-100 is a proprietary preservative-free formulation of IV ketamine that the company submitted to regulators as a treatment for acute suicidal crises in ...

2. nature.com nature.com/articles/s41398-024-02973-1

A meta-analysis of the effects of ketamine on suicidal ... Ketamine has been shown to reduce suicidal ideation rapidly, but the strength of the effect is unclear and there is little evidence-based medical evidence to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10524067/

Ketamine for bipolar depression: an updated systematic review A total of 48% of participants receiving ketamine achieved a response (defined as ⩾50% reduction in baseline depression severity), whereas only 5% achieved a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01944293

Ketamine for Suicidality in Bipolar Depression This study is designed to compare the effectiveness of two medications, Ketamine and Midazolam, for rapidly relieving suicidal thoughts in people suffering from ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7329804/

Efficacy of single and repeated administration of ketamine in ... At 2–3 weeks of repeated ketamine treatment, significant reduction of depression severity scores was observed: SMD = − 0.70; 95% CI − 1.15; − 0.25 or SMD = − ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40774133/

Risk of manic switch and suicidal outcomes in bipolar ... The primary outcomes were suicide-related events and manic switches across 1-7, 1-30, 1-90, 1-180, and 1-365 day intervals.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03396601?term=d%20cycloserine%20hydrochloride&viewType=Table&checkSpell=&rank=6

Study Details | NCT03396601 | NRX100 vs. Placebo for ... This study will test the hypothesis that that NRX-100 is superior to placebo in achieving rapid reduction in symptoms of depression and suicidal ideation in ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8299822/

Ketamine for Bipolar Depression: A Systematic Review - PMC Overall, our findings—derived from 6 studies—indicate that ketamine appears to be an effective and relatively safe treatment for BD and TRBD. All 6 studies in ...