Ketamine + Cognitive Training for Suicidal Behavior

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Rebecca Price

Must not be taking: St John's Wort

Disqualifiers: Psychosis, Pregnancy, Substance withdrawal, 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: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of a single intravenous dose of ketamine to quickly reduce suicidal thoughts in hospital patients. After receiving ketamine, participants will undergo either computer-based cognitive training (also known as cognitive therapy or neurocognitive training) or a sham version to determine if it extends ketamine's benefits. The researchers aim to find a faster and more accessible way to treat suicidality by enhancing the brain's learning capacity. Ideal participants are those hospitalized for suicidal behavior and referred for psychiatric consultation. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking St John's Wort.

What is the safety track record for these treatments?

Research shows that a single dose of ketamine administered through an IV is generally safe for short-term use in individuals with suicidal thoughts. In several studies, more than half of the participants experienced a rapid decrease in the intensity of their suicidal thoughts within 24 hours of receiving ketamine. Some side effects occurred, but they were usually mild and temporary, often including dizziness, nausea, and a feeling of disconnection from reality, which typically resolved on their own.

Ketamine has been studied in various settings and is already FDA-approved for other uses, indicating its safety when used under medical supervision.

The cognitive training component of the study employs techniques similar to cognitive behavioral therapy (CBT), which has proven effective and safe in reducing suicidal thoughts and behaviors. This training helps individuals change negative thought patterns and is considered safe for most people.

Overall, the combination of treatments in this trial has a strong safety record based on past research, with most side effects being manageable and temporary. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for suicidal behavior, which often include antidepressants and psychotherapy, the combination of ketamine and cognitive training offers a novel approach. Ketamine, administered intravenously, has a unique mechanism of action as an NMDA receptor antagonist, which can rapidly reduce symptoms of depression and suicidal thoughts. Researchers are excited because ketamine can potentially show results in just hours or days, compared to the weeks traditional therapies might take. Additionally, combining ketamine with cognitive training could enhance the long-term effectiveness of treatment by addressing both the biological and psychological aspects of suicidal behavior.

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

Research has shown that a single dose of ketamine administered through an IV can quickly reduce suicidal thoughts. In more than half of the patients, these thoughts decreased within 24 hours of treatment. Another study found that multiple ketamine infusions improved overall functioning in people with severe depression and suicidal thoughts. Additionally, ketamine has significantly reduced symptoms of depression, which often link to suicidal behavior. This trial will evaluate the effectiveness of ketamine combined with cognitive training, as well as ketamine with sham training, in treating suicidal thoughts. The trial will also assess the impact of cognitive training alone, without ketamine infusion, on suicidal behavior. ^{6 7 8 9 10}

Who Is on the Research Team?

Rebecca B Price, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 who are hospitalized, experiencing suicidality, and need psychiatric hospitalization. They must be able to consent and not have a history of severe reactions to ketamine or certain mental conditions like acute psychosis or developmental disorders with significant impairments.

Inclusion Criteria

My doctor agrees I am a good candidate for ketamine treatment in the hospital.

I understand the study requirements and have signed the consent form.

I was referred for a psychiatric evaluation due to feeling suicidal and need to be hospitalized.

Exclusion Criteria

Current pregnancy or breastfeeding

You have had a bad reaction or are allergic to ketamine or esketamine in the past.

I am currently taking St John's Wort.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of intravenous ketamine and undergo cognitive training

1 week

1 visit (in-person)

Post-Treatment Assessment

Participants are assessed for pain intensity, neuropathic pain quality, and satisfaction with treatment

5 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including suicidal behaviors and ideation

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive training
• Intravenous ketamine

Trial Overview The study tests if a single dose of intravenous ketamine can reduce suicidal thoughts quickly. It also examines whether combining this treatment with computer-based cognitive training can extend its benefits.

How Is the Trial Designed?

Group I: Ketamine + Cognitive Training Experimental Treatment 2 Interventions

Group II: No-infusion (TAU) + Cognitive Training Active Control 1 Intervention

Group III: Ketamine + Sham Training Placebo Group 2 Interventions

Group IV: No-infusion (TAU) + Sham Training Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Rebecca Price

Lead Sponsor

Trials

8

Recruited

820+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

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 156 suicidal patients, ketamine infusions significantly reduced suicidal ideation, with early remission at day 1 and day 3 being strong predictors of sustained remission at week 6.

Clinical factors like bipolar disorder and lower initial suicidal thoughts were linked to early remission, but overall, no specific clinical factors reliably predicted long-term outcomes, highlighting the need for ongoing monitoring and comprehensive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical predictive factors and trajectories of suicidal remission over 6 weeks following intravenous ketamine for suicidal ideation. Jollant, F., Demattei, C., Fabbro, P., et al.[2023]

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]

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 201 adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD), intravenous (IV) ketamine significantly reduced symptoms of anxiety, irritability, and agitation in those with mixed features, indicating its effectiveness in treating these symptoms.

Participants with anxiety, irritability, and agitation (AIA) experienced greater reductions in overall depressive symptoms and suicidal ideation compared to those without AIA, suggesting that IV ketamine could be a rapid treatment option for adults with mood disorders presenting with mixed features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. McIntyre, RS., Lipsitz, O., Rodrigues, NB., et al.[2021]

Citations

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

The effect of a single dose of intravenous ketamine on ... We found that across 10 controlled trials, a single ketamine infusion rapidly reduced the severity of suicidal thinking within 24 hours in more than half the ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032722001823

The effectiveness of repeated intravenous ketamine on ... Six infusions of ketamine was associated with improvements in functional outcomes in adults with TRD and/or suicidality.

3. psychiatryadvisor.com psychiatryadvisor.com/features/ketamine-rapid-antisuicidal-effects-mdd-mechanisms/

Ketamine for Suicidality: Evidence on Rapid Effects ... Their findings revealed that IV ketamine infusion led to significant reductions in depressive symptoms (β= -11; P <.001), as assessed by the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04154150

Ketamine + Cognitive Training for Suicidality in the Medical ... This project seeks to identify the acute and longer-term impact of a single dose of intravenous ketamine among suicidal patients referred for psychiatric ...

5. nature.com nature.com/articles/s41398-021-01327-5

Acute cognitive effects of single-dose intravenous ketamine ... Intravenous (IV) subanesthetic doses of ketamine have been shown to reduce psychiatric distress in both major depressive (MDD) and posttraumatic stress ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2888910/

Cognitive Behavior Therapy for Suicide Prevention (CBT-SP) CBT-SP consists of acute and continuation phases, each lasting about 12 sessions, and includes a chain analysis of the suicidal event, safety plan development, ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2826055

Telehealth Brief Cognitive Behavioral Therapy for Suicide ... The findings of this randomized clinical trial suggest that BCBT delivered via video telehealth is effective for reducing suicide attempts.

8. sprc.org sprc.org/resources/cognitive-behavioral-therapy-for-suicidal-behavior/

Cognitive Behavioral Therapy for Suicidal Behavior This webinar will review the basic principles of cognitive behavioral therapy (CBT) and discuss CBT for patients with suicidal behavior.

9. jwatch.org jwatch.org/na59343/2025/10/28/brief-cognitive-behavioral-therapy-tested-prevent-suicide

Brief Cognitive-Behavioral Therapy Tested to Prevent ... In CBT, the goal was to address the emotional and cognitive states tied to suicidal thinking. PCT — proven effective to treat depression and ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032722009235

The significance of cognitive-behavioral therapy on suicide Based on the current evidence, CBT could relieve suicide, including suicide ideation, suicide attempts. CBT is scalable and cost-effective.