Ketamine for Suicidal Thoughts

Overseen By Research Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: The Royal's Institute of Mental Health Research

Must not be taking: Ketamine

Disqualifiers: Uncontrolled hypertension, Diabetes, Psychosis, 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: 6

Duration: 2 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if ketamine, an anesthetic, can reduce suicidal thoughts in individuals with Major Depressive Disorder (MDD). Researchers seek to understand how ketamine might alter brain activity and thought patterns through MRI scans and interviews. Participants will receive four ketamine infusions over two weeks and undergo two MRI scans. Individuals diagnosed with MDD and experiencing active suicidal thoughts may be suitable for this study. As a Phase 2/3 trial, this research evaluates ketamine's effectiveness and represents the final step before potential FDA approval, offering participants an opportunity to contribute to significant advancements in treatment.

Will I have to stop taking my current medications?

The trial requires that you keep taking your current medications at the same doses throughout the study.

Is there any evidence suggesting that ketamine is likely to be safe for humans?

Research has shown that ketamine can quickly reduce suicidal thoughts, often within just one day of treatment. Studies have found that its effects can last up to a week in people with depression who also experience suicidal thoughts. This is promising for those considering ketamine as a treatment option.

Regarding safety, ketamine is usually well-tolerated in controlled settings. However, limited information exists about its long-term use. While ketamine appears safe for short-term treatment, the effects of prolonged use remain unclear. Participants should consider this when deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for suicidal thoughts, which often include antidepressants or psychotherapy, ketamine offers a unique and rapid-acting solution. Ketamine works differently by targeting the brain's glutamate system, which can help alleviate symptoms much faster than traditional methods that focus on serotonin. Researchers are excited because ketamine can show results in just a matter of days, providing a potentially life-saving option for those in acute crisis. Additionally, its use as an intravenous infusion allows for precise dosing and quick onset of action.

What evidence suggests that ketamine might be an effective treatment for suicidal thoughts in MDD?

Research has shown that ketamine, which participants in this trial will receive, can quickly reduce suicidal thoughts in people with depression. In one study, ketamine reduced these thoughts within a day, and the effects lasted up to a week. Another study found that 55% of participants who received ketamine no longer had significant suicidal thoughts by the third day. These findings suggest that ketamine effectively reduces suicidal thoughts rapidly in people with major depressive disorder. ^{1 2 6 7 8}

Who Is on the Research Team?

Jennifer Phillips, PhD

Principal Investigator

University of Ottawa Institute for Mental Health Research at The Royal

Are You a Good Fit for This Trial?

This trial is for individuals with Major Depressive Disorder who are currently experiencing suicidal thoughts. Participants must be eligible for MRI scans and willing to undergo multiple ketamine infusions as well as interviews and assessments.

Inclusion Criteria

Must be English speaking

Suicidal ideation severity score ≥3 on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening Visit

I have been diagnosed with Major Depressive Disorder.

Exclusion Criteria

History of a primary psychotic disorder or current/recent acute episode of psychosis

Current or recent history of substance use/dependence or problematic alcohol use

History of significant head injury including loss of consciousness >5 minutes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive four IV ketamine infusions administered twice weekly for two weeks

2 weeks

4 visits (in-person)

Neuroimaging and Assessment

Participants undergo MRI scans and assessments of suicidal ideation and depressive symptoms

3 weeks

2 MRI sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview The study tests if ketamine can reduce suicidal ideation in MDD patients. It involves four IV ketamine treatments over two weeks, with MRIs before the first treatment and after the last one, plus regular mental health assessments.

How Is the Trial Designed?

Group I: Ketamine Experimental Treatment 1 Intervention

Participants will undergo a total of four IV ketamine infusions (0.5 mg/kg infused over 40 minutes), administered twice weekly for two weeks.

Who Is Running the Clinical Trial?

The Royal's Institute of Mental Health Research

Lead Sponsor

Trials

8

Recruited

1,300+

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 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 295 outpatients receiving intravenous ketamine treatment for suicidality, three distinct groups emerged based on their response to treatment, with 57.6% showing gradual improvement in suicidal symptoms over five infusions.

Among patients with severe suicidal thoughts at baseline, those with higher scores for active thoughts of death were less likely to benefit from ketamine treatment, highlighting the need for careful patient selection in this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-suicidal effects of IV ketamine in a real-world setting. O'Brien, B., Lee, J., Kim, S., et al.[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]

A systematic review of 12 randomized controlled trials found that subanesthetic ketamine, particularly in intravenous form at a dose of 0.5 mg/kg, significantly reduces suicidal ideation in acutely depressed patients, with effects observed within hours.

The benefits of ketamine for reducing suicidal thoughts can last beyond 24 hours, with one study showing sustained improvement up to six weeks after a single dose, although further research is needed to confirm long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rapid anti-suicidal ideation effect of ketamine: A systematic review. Hochschild, A., Grunebaum, MF., Mann, JJ.[2021]

In a case series of five inpatients with major depressive disorder and suicidal ideation, six infusions of ketamine led to an impressive 84% reduction in suicidal ideation scores and a 47% reduction in depression scores over approximately 12 days.

The study suggests that serial ketamine infusions are safe and feasible for reducing suicidal thoughts and depressive symptoms, although the small sample size highlights the need for larger randomized controlled trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting. Sinyor, M., Williams, M., Belo, S., 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]

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]

A review of 34 articles revealed 312 cases of overdose and 138 deaths related to ketamine use, primarily in recreational settings and often involving polydrug use, highlighting significant risks associated with misuse.

Despite concerns about ketamine's safety in non-medical contexts, no overdoses or deaths were reported from its use as an antidepressant in therapeutic settings, suggesting it can be safely prescribed when used appropriately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overdoses and deaths related to the use of ketamine and its analogues: a systematic review. Chaves, TV., Wilffert, B., Sanchez, ZM.[2023]

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]

Citations

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

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

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

A meta-analysis of the effects of ketamine on suicidal ... A growing body of research suggests that ketamine and esketamine may rapidly reduce suicidal ideation in depressed subjects at risk for suicide ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584624002203

Efficacy of single and repeated ketamine administration for ... Previous studies have demonstrated rapid-onset anti-suicidal ideation effects of ketamine. This study aimed to compare the efficacy and duration of anti ...

4. mghpsychnews.org mghpsychnews.org/anti-suicidal-effects-of-iv-ketamine/

Ketamine Rapidly Reduces Suicidal Ideation, But How ... At day 3, 22 of 40 (55.0%) of participants receiving IV ketamine no longer reported clinically significant suicidal ideation, compared to 7 out of 16 (43.8%) of ...

5. bmcresnotes.biomedcentral.com bmcresnotes.biomedcentral.com/articles/10.1186/s13104-024-07029-7

Is ketamine efficacious for rapid treatment of acute suicidal ... They reported that two 40-minute IV doses of ketamine significantly reduced suicidal ideation on day three (to a score of lower than 3) (odds ...

6. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2019.19050508

All Suicidal Ideation Is Not Created Equal: Two Cases of ... We have limited safety data on long-term ketamine use, such as data on tolerance, withdrawal, and possible risks associated with discontinuation ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0091743521001080

The rapid anti-suicidal ideation effect of ketamine Ketamine rapidly reduces suicidal ideation [SI] in depressed patients and how long the benefit persists after one dose and if the route of administration or ...

8. yalemedicine.org yalemedicine.org/clinical-trials/ketamine-for-adolescent-suicidality

Ketamine for Adolescent Suicidality The purpose of this study is to determine if intravenous ketamine reduces suicidal thinking compared to an active placebo (midazolam) in adolescents.