Ketamine for Suicide Attempts

Recruiting at 1 trial location

Overseen By Christina Deisz, LISW-S

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Tatiana Falcone, MD

Must not be taking: Phencyclidine, Cocaine, Amphetamines

Disqualifiers: Autism, Schizophrenia, Substance use, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 6

Duration: 2 weeks

62 Participants Needed

Trial Summary

What is the purpose of this trial?

Ketamine, an NMDA antagonist, has been shown to have rapid anti- suicidal effects. However, its safety and efficacy and special populations has not been investigated and documented. Several reports in adults suggest rapid decrease of suicidal ideation. In the last decade there is an alarming increase of the number of suicide attempts in patients ages 14-30. Suicide is the second leading cause of death in this population. Patients with previous history of suicide attempt, are even in a higher risk category. The present study focus in this high risk group of suicide attempters. This will be a randomized controlled trial enrolling 62 youth between the ages 14-30 after a suicide attempt; patients will be randomized to receive Ketamine 0.5 mg/kg over 40 minutes or normal saline. Patients will receive all Ketamine or placebo infusions while admitted in the Inpatient Psychiatry Service. Patients will receive up to 6 ketamine or placebo infusions until, for 3 consecutive sessions, they have a clinician rated Scale for Suicidal Ideation (SSI) score of\<4, and \>50% decrease from baseline, and clinical assessment of patient not being suicidal, or they have been discharged from the inpatient unit. Patients will participate in weekly sessions of Collaborative Assessment for the management of Suicidality (CAMS), from the first week of the study while admitted to the hospital and will continue it on a weekly basis post-discharge until the patient has three consecutive outpatient CAMS sessions with an overall risk \< 2 (# 6 on the SSF Core Assessment) along with a positive response regarding their thoughts/feelings and clinician indicating behavioral stability (suicidal behavior).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking drugs that significantly interact with ketamine, you may not be eligible to participate.

What evidence supports the effectiveness of the drug ketamine for reducing suicide attempts?

Research shows that ketamine, given in low doses, can quickly reduce suicidal thoughts in people with depression, with effects appearing within an hour and lasting up to a week. Studies suggest it may be a useful crisis intervention for those at risk of suicide, with many patients experiencing significant improvement. ^{1 2 3 4 5}

Is ketamine safe for treating suicide attempts?

Research suggests that ketamine can be a safe and effective treatment for reducing suicidal thoughts, with rapid and lasting effects. However, some studies report potential adverse events, such as apnea (temporary stopping of breathing), so careful monitoring is recommended during treatment. ^{2 6 7 8 9}

How is the drug ketamine unique in treating suicide attempts?

Ketamine is unique because it can rapidly reduce suicidal thoughts within hours of a single low-dose infusion, unlike traditional treatments that may take weeks to show effects. It is administered intravenously and has been shown to have lasting benefits for up to six months, making it a novel option for crisis intervention in patients at high risk of suicide. ^{1 2 3 7 10}

Research Team

Tatiana Falcone, M.D.

Principal Investigator

The Cleveland Clinic

Amit Anand, M.D.

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for young individuals aged 14-30 who have attempted suicide and are currently experiencing suicidal thoughts. They must understand the study and agree to participate. Exclusions include those with certain mental health conditions, intellectual disabilities, recent drug abuse, or specific medical contraindications.

Inclusion Criteria

I am between 14 and 30 years old.

Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Subjects must have been admitted to Fairview Hospital or Massachusetts General Hospital (Blake 11) after a suicide attempt (any intentional, non-fatal self- injury regardless of medical lethality, if intent to die was indicated) with continued suicidal ideation or endorsing ongoing suicidal ideation and unable to contract for safety placing them at an increased risk to attempt suicide. Subjects will need a clinical rated Scale for Suicidal Ideation (SSI) score ≥ 6.

Exclusion Criteria

Subjects with history of moderate or severe substance or alcohol use per DSM- V criteria in the past 6 months.

You have been diagnosed with autism or are unable to speak.

Within 6 months before initial screening, urine toxicology positive for phencyclidine, cocaine or amphetamines (subjects prescribed amphetamines for management of ADHD will not be excluded).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive up to 6 ketamine or placebo infusions over two weeks while admitted in the Inpatient Psychiatry Service

2 weeks

Up to 6 visits (inpatient)

Collaborative Assessment for the Management of Suicidality (CAMS)

Weekly CAMS sessions are conducted during inpatient stay and continue post-discharge until criteria for reduced suicidal ideation are met

Up to 3 months post-discharge

Weekly sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with monthly assessments for suicidal ideation, attempts, and readmissions

3 months

Monthly assessments

Treatment Details

Interventions

• CAMS Therapy
• Ketamine Hydrochloride

Trial Overview The trial tests Ketamine's ability to reduce suicidal thoughts in youth after a suicide attempt. Participants will receive either Ketamine or saline while hospitalized and undergo CAMS Therapy weekly during and after hospitalization until they show significant improvement in their condition.

Participant Groups

Group I: Ketamine Treatment + CAMS Therapy Experimental Treatment 2 Interventions

Group II: Saline Placebo Treatment + CAMS Therapy Placebo Group 2 Interventions

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?

Tatiana Falcone, MD

Lead Sponsor

Trials

1

Recruited

140+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Findings from Research

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]

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 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 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 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 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]

Ketamine hydrochloride has shown rapid and significant antidepressant effects in patients with treatment-resistant mood and anxiety disorders, although the studies supporting this have small sample sizes and limited long-term data.

While ketamine may offer benefits for some patients, there are important safety concerns and limitations in the existing research that must be considered when using it as an off-label treatment for psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. Sanacora, G., Frye, MA., McDonald, W., et al.[2022]

Ketamine shows promise as a treatment for treatment-resistant depression (TRD), but its use can lead to common adverse events, which are usually temporary.

A case of apnea during a slow sub-anesthetic infusion of ketamine highlights a rare but serious potential side effect, emphasizing the need for careful monitoring and management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. Gómez-Revuelta, M., Fernández-Rodríguez, M., Boada-Antón, L., et al.[2021]

In a randomized controlled trial involving 57 patients with treatment-resistant depression, intravenous ketamine significantly reduced explicit suicidal thoughts within 24 hours compared to a placebo (midazolam), with 53% of ketamine-treated patients showing no suicidal ideation at that time.

Ketamine also decreased implicit suicidal cognition, as measured by the Implicit Association Test, indicating its potential to rapidly alter both conscious and unconscious suicidal thoughts, particularly in those with higher baseline suicidal ideation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Price, RB., Iosifescu, DV., Murrough, JW., et al.[2022]

References

1. 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]

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

Ketamine Use for Suicidal Ideation in the General Hospital: Case Report and Short Review. [2022]

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

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

4. Ireland pubmed.ncbi.nlm.nih.gov

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting. [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. United States pubmed.ncbi.nlm.nih.gov

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. [2021]

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

Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. [2022]