Ketamine + Crisis Response Plan for Suicidal Thoughts

Overseen By Stehanie Perez, MHA

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Ketamine

Disqualifiers: Psychosis, Intoxication, Pregnancy, Cardiovascular, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 60 minutes

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with severe suicidal thoughts who visit the Emergency Department. It tests a combination of a single dose of ketamine (a medication often used for pain relief) and a short, focused therapy session called a Crisis Response Plan. The goal is to determine if this combination can quickly reduce suicidal feelings more effectively than usual care. This trial may suit adults visiting the Emergency Department with urgent suicidal thoughts who are being admitted to a psychiatric unit. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

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's best to discuss this with the study team or your doctor.

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

Research has shown that ketamine has been tested in various studies for its impact on suicidal thoughts. One study found that ketamine quickly reduced suicidal thoughts in people with major depression, suggesting it might work fast to lessen these thoughts. Most participants tolerated ketamine well, though some experienced mild side effects like dizziness and nausea.

Crisis response plans (CRP) have also significantly reduced suicidal thoughts and actions. A CRP provides a step-by-step guide for use during a crisis, offering a safe and supportive way to cope.

Both ketamine and CRP have shown promise in past studies, indicating they are generally safe and might help reduce suicidal thoughts. However, as with any treatment, results can vary from person to person. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using ketamine for suicidal thoughts because it offers a new approach compared to traditional treatments like antidepressants and psychotherapy, which often take weeks to show effects. Ketamine acts on the brain's glutamate system, providing rapid relief from suicidal thoughts, potentially within hours. Additionally, its use in combination with a Crisis Response Plan (CRP) could offer a comprehensive strategy that addresses immediate mental health needs and provides tools for coping, setting it apart from standard care.

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

Research has shown that ketamine, which participants in this trial may receive, can quickly reduce suicidal thoughts. In studies, patients who received ketamine experienced a significant decrease in suicidal thinking within 24 hours, making it a promising option for people in crisis. Similarly, the Crisis Response Plan (CRP), also part of the experimental arm in this trial, has effectively reduced suicidal thoughts and attempts. People using CRP were much less likely to harm themselves in the following months. Together, these treatments might offer fast and lasting help to those with intense suicidal thoughts. ^{3 6 7 8 9}

Who Is on the Research Team?

Robert De Lorenzo, MD, MSM

Principal Investigator

UT Health San Antonio

Romeo Fairley, MD, MPH

Principal Investigator

UT Health San Antonio

Alan Peterson, PhD, ABPP

Principal Investigator

UT Health San Antonio

Stacey Young-McCaughan, RN, PhD

Principal Investigator

UT Health San Antonio

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 who come to the Emergency Department with urgent suicidal thoughts and are cleared for psychiatric admission. They must be able to understand the study, consent voluntarily, and have a working phone for follow-ups. Excluded are those intoxicated, pregnant or breastfeeding, recent ketamine users, prisoners, under law enforcement custody unless released, or with severe physical/mental health conditions.

Inclusion Criteria

I am approved for admission to the psychiatric unit at University Hospital.

Decision to admit the patient to the inpatient unit or psychiatric stabilization unit made prior to consent to prevent study procedures from complicating or influencing the disposition and treatment as usual for suicidal patients reporting to the ED

Able to read and write English

Exclusion Criteria

Patient is a prisoner

Serious mental illness with active and significant signs of psychosis, mania, hallucinations, paranoia, agitation, and drug-induced or other toxidromic symptoms

Pregnancy or breast feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a one-time dose of 100mg intramuscular ketamine and complete a Crisis Response Plan in the Emergency Department

60 minutes

1 visit (in-person)

Immediate Monitoring

Participants are monitored for 45 minutes post-ketamine administration with pulse oximetry and recurrent vital signs

45 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 2 hours, 3 days, and 1 month post-intervention

30 days

Telephone interviews and/or visits

What Are the Treatments Tested in This Trial?

Interventions

• Crisis Response Plan
• Ketamine Hydrochloride

Trial Overview The trial tests if one dose of intramuscular ketamine (100mg) combined with a Crisis Response Plan can reduce suicidal thoughts in emergency department patients more effectively than current methods. It also explores whether weight-based dosing could improve outcomes.

How Is the Trial Designed?

Group I: Ketamine and Crisis Response Plan (CRP) Experimental Treatment 2 Interventions

Individuals randomized to the experimental arm will receive 100mg intramuscular ketamine injection before completing the Crisis Response Plan. The average timeframe for the experimental arm is anticipated to be approximately 60 minutes of active treatment. Following ketamine administration, the subject will be monitored for 45 minutes with pulse oximetry and recurrent vital signs. The study team will record when the CRP is completed in relation to the ketamine injection.

Group II: Treatment as Usual Active Control 1 Intervention

Individuals randomized to the no intervention arm will receive routine care from emergency providers and psychiatry staff.

Ketamine Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Pain management
• Depression
• Suicidal ideation

Approved in European Union as Ketamine Hydrochloride for:

• Anesthesia
• Pain management
• Treatment-resistant depression

Approved in Canada as Ketamine Hydrochloride for:

• Anesthesia
• Pain management
• Depression

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

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]

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]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

In a systematic review of 93 studies involving 3756 participants receiving sub-anesthetic doses of ketamine for psychiatric disorders, only four serious adverse medical events (MSAEs) were reported, resulting in an incidence of approximately 0.1%, indicating a very low risk of serious complications.

No serious cardiac events or deaths were observed, and most studies effectively screened out high-risk patients, suggesting that with proper medical screening, ketamine can be administered safely for psychiatric treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. Hovda, N., Gerrish, W., Frizzell, W., et al.[2023]

In a study of 14 outpatients with treatment-resistant depression and stable suicidal thoughts, ketamine infusions significantly reduced suicidal ideation, with 50% of participants showing remission during the treatment phase.

The effects of ketamine were rapid and robust, with some patients maintaining reduced suicidal thoughts for up to 3 months after treatment, indicating its potential as a critical intervention for those at risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study. Ionescu, DF., Swee, MB., Pavone, KJ., et al.[2022]

In a study of 80 adults with major depressive disorder and significant suicidal ideation, those receiving adjunctive ketamine showed a 4.96-point greater reduction in suicidal thoughts compared to those receiving midazolam within 24 hours.

Ketamine treatment resulted in a 55% response rate (≥50% reduction in suicidal ideation) compared to 30% for midazolam, indicating its potential as a rapid intervention for suicidal ideation in depression, with effects lasting up to 6 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Grunebaum, MF., Galfalvy, HC., Choo, TH., et al.[2022]

Low-dose ketamine infusion has shown rapid effects in reducing suicidal thoughts, making it a potentially valuable treatment in general hospital settings for patients at risk of suicide.

The treatment was reported to be efficient and well-tolerated in a patient who had recently attempted suicide, suggesting a favorable benefit-risk ratio for its use in acute care situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Use for Suicidal Ideation in the General Hospital: Case Report and Short Review. Vulser, H., Vulser, C., Rieutord, M., et al.[2022]

A single intravenous infusion of ketamine (0.5 mg/kg) significantly reduces suicidal ideation within 4 hours and this effect can last up to 72 hours after treatment, based on a systematic review of 15 trials involving 572 participants.

While ketamine shows promise for short-term relief of suicidal thoughts, there is limited data on its long-term effects and actual suicidal behaviors, indicating a need for further research to sustain its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials. Witt, K., Potts, J., Hubers, A., et al.[2020]

Ketamine has shown promising antidepressant and antisuicidal effects in adults, and recent studies indicate it may also be effective in adolescents, with the first placebo-controlled trial in 2021 demonstrating its superiority over midazolam.

While initial findings suggest that ketamine acts quickly to alleviate depression and reduce suicidal thoughts in adolescents, the studies conducted so far are small, highlighting the need for further research to confirm these results and guide clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Use in Child and Adolescent Psychiatry: Emerging Data in Treatment-Resistant Depression, Insights from Adults, and Future Directions. Ryan, K., Hosanagar, A.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10189833/

Effectiveness of Suicide Safety Planning Interventions Evidence across a range of studies indicates that SSP is effective for reducing suicide behavior (SB) and ideation (SI).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0887618523001627

Crisis response planning rapidly reduces suicidal ideation ... Crisis response planning (CRP), a brief safety planning-type intervention, has been shown to rapidly reduce suicidal ideation and suicide attempts.

3. msrc.fsu.edu msrc.fsu.edu/blog/msrc-common-data-elements-cde/

Crisis Response Plan (CRP) Results indicated Soldiers who received a CRP were 76% less likely to attempt suicide during the next six months as compared to Soldiers who received standard ...

4. bmchealthservres.biomedcentral.com bmchealthservres.biomedcentral.com/articles/10.1186/s12913-024-11739-w

insights from a randomized control trial of crisis response plan ... Both Crisis Response Plan and self-guided Safety Planning were found to lower suicidality after receiving them via telehealth services.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11681889/

Comparison of crisis response planning and treatment as ... This study will compare the longitudinal effects of crisis response planning (CRP) and treatment as usual (TAU) on suicidal thoughts and behaviors among active ...

6. suny.edu suny.edu/mental-health/resources/

Find Mental Health Resources Near You Services Offered. Individual counseling; Group counseling; Wellness programming; Consultation; Crisis intervention; Educational programs (classes, dorms) ...

7. mirecc.va.gov mirecc.va.gov/visn19/cpg/recs/7/

7: Crisis Response Planning and Safety Planning Crisis Response Plans (CRP) and Safety Planning (SPI) both include step-by-step instructions to use prior to or during a suicidal crisis.

8. sprc.org sprc.org/resources/stanley-brown-safety-plan/

Stanley-Brown Safety Plan A brief intervention to help those experiencing self-harm and suicidal thoughts with a concrete way to mitigate risk and increase safety.

9. zerosuicide.edc.org zerosuicide.edc.org/toolkit/evidence-base/engage

Engage | Zero Suicide - edc.org It is essential to continuously assess risk, engage patients in their collaborative safety plan, treatment plan, and suicide care management plan and re-engage ...