IM Ketamine vs Midazolam for Suicidal Thoughts

Overseen By Sumra Sajid, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: New York State Psychiatric Institute

Disqualifiers: Substance use, Psychosis, Mania, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 2 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two treatments, ketamine (ketamine hydrochloride injection) and midazolam (midazolam injection), to quickly reduce suicidal thoughts in people with severe depression in the emergency department. The goal is to identify an effective, easy-to-use treatment to prevent suicide in high-risk patients. Participants include individuals experiencing a major depressive episode and seeking help in the emergency department due to suicidal thoughts. The trial is not enrolling new participants due to a pause in research activities. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

What is the safety track record for these treatments?

Research has shown that ketamine has been used successfully to treat depression and reduce suicidal thoughts, even though the FDA has not approved it for these uses yet. Studies have found that ketamine can quickly lessen suicidal thoughts, sometimes within hours, and most people tolerate it well. However, some safety concerns exist. The FDA has warned about risks related to compounded ketamine, a version made by special pharmacies.

Midazolam, another treatment in the trial, often helps with anxiety or muscle relaxation. It is generally considered safe for short-term use in medical settings.

Overall, while ketamine shows promise, it is important to be aware of potential risks, as with any treatment. Discuss any concerns with healthcare providers. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike traditional treatments for suicidal thoughts, which often involve oral medications and psychotherapy, ketamine hydrochloride is unique because it works rapidly, showing potential effects in just a few hours. This is in stark contrast to standard antidepressants, which can take weeks to become effective. Ketamine functions by targeting the brain's glutamate system rather than the serotonin system, offering a novel approach to managing acute suicidal ideation. Researchers are excited about ketamine's potential to provide immediate relief, which could be life-saving for individuals in crisis.

What evidence suggests that this trial's treatments could be effective for suicidal thoughts?

Research shows that ketamine, which participants in this trial may receive, can quickly reduce suicidal thoughts in people with depression. Studies have found that ketamine leads to a fast and significant drop in intense suicidal thinking, with effects noticeable within hours and lasting up to a week. For instance, one study observed a significant decrease in suicidal thoughts just 40 minutes after a ketamine injection. This makes ketamine a promising option for those needing immediate help during high-risk times. In this trial, midazolam serves as a comparison treatment, but current research highlights ketamine's ability to quickly ease suicidal thoughts. ^{2 6 7 8 9}

Who Is on the Research Team?

Michael Grunebaum, MD

Principal Investigator

New York State Psychiatric Institute/Columbia University Irving Medical Center

Are You a Good Fit for This Trial?

This trial is for adults in the emergency department with severe depression and suicidal thoughts who need hospitalization. They must have a certain score indicating suicidality, be experiencing a major depressive episode, and agree to stay in the hospital. It's not for pregnant women, those unable to consent or understand English, people with unstable health conditions like uncontrolled high blood pressure or heart issues, recent substance abuse, psychosis or mania, or intellectual disability.

Inclusion Criteria

A Beck Scale for Suicidal Ideation score of 4 or higher suggests that you may be suicidal

I have been diagnosed with a major depressive episode.

I was advised to get inpatient treatment for suicidal thoughts by a psychiatrist.

Exclusion Criteria

I cannot take ketamine or midazolam due to health reasons.

I do not have any uncontrolled serious health conditions.

You have used drugs or alcohol excessively in the past two weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive a single IM injection of ketamine or midazolam and are monitored for effects

2 hours

1 visit (in-person)

Inpatient Monitoring

Participants are admitted to the inpatient unit for standard clinical treatment and monitoring

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after discharge

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine hydrochloride injection
• Midazolam injection

Trial Overview The study tests if an injection of ketamine can quickly reduce suicidal thoughts in patients compared to midazolam (a sedative). Participants are given one of these drugs while they're in the emergency room being evaluated for serious mental health concerns.

How Is the Trial Designed?

Group I: Ketamine Experimental Treatment 1 Intervention

Ketamine hydrochloride 0.5 mg/kg IM single injection

Group II: midazolam Active Control 1 Intervention

Midazolam 0.06 mg/kg IM single injection

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

A pilot study involving 16 participants with bipolar depression indicated that a sub-anesthetic dose of ketamine (0.5 mg/kg) may lead to a greater reduction in suicidal ideation compared to midazolam, with a mean difference of nearly 6 points on the Scale for Suicidal Ideation, although this was not statistically significant.

The study found promising correlations between memory improvement and reduction in suicidal thoughts after ketamine infusion, as well as a decrease in serum brain-derived neurotrophic factor (BDNF) associated with reduced suicidal ideation, suggesting potential biomarkers for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. Grunebaum, MF., Ellis, SP., Keilp, JG., et al.[2022]

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]

In a study involving 151 participants from 10 clinical trials, it was found that the placebo response for suicidal ideation was greater than for other depressive symptoms when participants received saline or midazolam, suggesting that suicidal thoughts may respond differently to treatment than general depression symptoms.

These findings may help explain why intravenous ketamine shows rapid improvements in overall depressive symptoms but has more modest effects on suicidal ideation, indicating a need for further research into targeted treatments for suicidal thoughts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine. Bloomfield-Clagett, B., Ballard, ED., Greenstein, DK., et al.[2023]

In a study of 42 newly-diagnosed cancer patients, a single dose of ketamine significantly reduced suicidal ideation and overall depression levels compared to midazolam, with improvements noted as early as day 1 and continuing to day 3.

The findings highlight ketamine's potential as a rapid antidepressant for patients facing acute depression and suicidal thoughts, suggesting it may be an effective intervention in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine rapidly relieves acute suicidal ideation in cancer patients: a randomized controlled clinical trial. Fan, W., Yang, H., Sun, Y., et al.[2022]

A single dose of ketamine can significantly reduce suicidal thoughts within an hour of administration, with effects lasting up to a week, making it a promising option for patients with severe or treatment-resistant depression.

The antisuicidal effects of ketamine occur independently of its impact on overall depression severity, indicating a unique mechanism of action that warrants further investigation for crisis intervention in suicidal patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible Use as Crisis Intervention in Patients at Suicide Risk. Andrade, C.[2022]

Citations

1. mecp.springeropen.com mecp.springeropen.com/articles/10.1186/s43045-024-00428-3

Ketamine's efficacy in alleviating acute suicidal thoughts Ketamine offers a rapid and significant reduction in acute suicidal ideation in patients with MDD. It holds promise as an intervention during high-risk periods.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4614623/

The Effect of Intravenous Ketamine in Suicidal Ideation ... The results like previous studies show that ketamine is effective in reducing suicidal ideations. Yet in our study, the SSI score 40 minutes after the injection ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05105061

NCT05105061 | Intramuscular Ketamine for Suicidal Ideation The objective of the present research protocol, a cross-over, subject-blinded, clinical trial, is to correlate changes in brain activity with reduction in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5794524/

The effect of a single dose of intravenous ketamine on ... Conclusions. Ketamine rapidly reduced suicidal thoughts within one day and for up to one week in depressed patients with suicidal ideation. Ketamine's effects ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/24705470221128017

(Es)Ketamine for Suicidal Ideation and Behavior: Clinical ... The increased dosage did not augment antisuicidal efficacy. At 3-month follow-up, 29% of acute phase responders maintained remission. By ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470357/

Ketamine - StatPearls - NCBI Bookshelf - NIH Ketamine is also used successfully for treatment-resistant depression and suicidal ideation, although it is not yet FDA-approved.[3]. Ketamine ...

7. journals.sagepub.com journals.sagepub.com/doi/10.1177/20451253231151327

Ketamine and esketamine in suicidal thoughts and behaviors We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary ...

8. fda.gov fda.gov/drugs/human-drug-compounding/fda-warns-patients-and-health-care-providers-about-potential-risks-associated-compounded-ketamine

FDA warns about compounded ketamine for psychiatric ... FDA has identified potential safety concerns associated with the use of compounded ketamine products from compounders and telemedicine platforms.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05696691

Ketamine & Crisis Response Plan for Suicidal Ideation in ... Determine if 100mg of IM ketamine and Crisis Response Plan in combination results in greater short-term reductions in suicidal ideation in adult patients ...