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

Trial Summary

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.

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

Research shows that ketamine can quickly reduce suicidal thoughts in people with depression, with effects appearing within an hour and lasting up to a week. Studies found that a single dose of ketamine has significant benefits in reducing suicidal thoughts, even in those with severe depression. ^{1 2 3 4 5}

Is ketamine safe for treating suicidal thoughts?

Ketamine, when used in a medical setting for psychiatric disorders, is generally considered safe, with no reported cases of overdose or death in therapeutic contexts. However, it is important to be cautious as misuse, especially in recreational settings, can be dangerous. ^{3 5 6 7 8}

How is the drug ketamine unique in treating 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. Unlike traditional antidepressants, which may take weeks to work, ketamine acts quickly and is administered intravenously in subanesthetic doses, making it a potential crisis intervention for those at immediate risk of suicide. ^{5 9 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to treat active suicidal ideation in individuals with Major Depressive Disorder (MDD) using ketamine and to understand suicidal ideation by examining biological mechanisms using magnetic resonance imaging (MRI), and psychological mechanisms through validated clinical scales and qualitative interviews. The main questions it aims to answer are: 1. Will ketamine will reduce suicidal ideation in a significant proportion of study participants? 2. Will reduction in suicidal ideation will be accompanied by rapid changes in neuroimaging biomarkers? Participants will receive four intravenous (IV) ketamine infusions administered twice weekly for two weeks. Participants will undergo two identical MRI scans: 1) within 48 hours prior to starting ketamine treatment, and 2) 24 hours after the fourth ketamine infusion. Suicidal ideation and depressive symptoms will be assessed prior to each imaging session alongside additional self-report measures. Qualitative interviews will occur within 72 hours after the fourth ketamine treatment.

Research Team

Jennifer Phillips, PhD

Principal Investigator

University of Ottawa Institute for Mental Health Research at The Royal

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials. [2020]

2. Ireland pubmed.ncbi.nlm.nih.gov

Anti-suicidal effects of IV ketamine in a real-world setting. [2023]

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

The rapid anti-suicidal ideation effect of ketamine: A systematic review. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting. [2022]

5. 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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. [2023]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Overdoses and deaths related to the use of ketamine and its analogues: a systematic review. [2023]

9. United States 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. [2022]

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

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. [2022]

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

Ketamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. [2022]