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

90 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug ketamine for reducing suicidal thoughts?

Research shows that ketamine can quickly reduce suicidal thoughts, with effects appearing within an hour and lasting up to a week. This has been observed in patients with depression and cancer, and ketamine's impact is greater than that of midazolam, another drug used in studies. ^{1 2 3 4 5}

Is ketamine safe for treating suicidal thoughts?

Ketamine has been used safely in medical settings for many years, and studies show it can quickly reduce suicidal thoughts. However, there are concerns about its long-term safety, especially with repeated use, as it can cause temporary changes in mental state. ^{1 2 3 6 7}

How does ketamine differ from other drugs for suicidal thoughts?

Ketamine is unique because it can rapidly reduce suicidal thoughts within an hour of administration and its effects can last up to a week, which is much faster than traditional antidepressants. It is administered as an injection, and unlike many other treatments, it works even in patients who have not responded to other depression treatments. ^{1 2 3 4 8}

What is the purpose of this trial?

This trial tests whether a shot of ketamine can quickly reduce suicidal thoughts in depressed adults who visit the emergency room. These patients are at high risk of suicide and need fast-acting treatment. Ketamine works by quickly changing brain chemicals to improve mood and reduce suicidal thoughts. It has been found to rapidly reduce depressive symptoms and suicidal thoughts, making it a potential fast-acting treatment for suicidality.

Research Team

Michael Grunebaum, MD

Principal Investigator

New York State Psychiatric Institute/Columbia University Irving Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

1. England 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. [2023]

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

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

3. Denmark pubmed.ncbi.nlm.nih.gov

Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. [2022]

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

Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression. [2021]

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

Ketamine rapidly relieves acute suicidal ideation in cancer patients: a randomized controlled clinical trial. [2022]

6. 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]

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

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: Results from a randomized double-blind study. [2022]