Ketamine vs Midazolam for Suicidal Thoughts

(TASK Trial)

Overseen By Zach Brown, BA

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: CYP3A4 inhibitors, CYP2B6 inducers

Disqualifiers: Psychotic disorder, Mania, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 16

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of ketamine (an anesthetic) compared to midazolam (a sedative) in rapidly reducing suicidal thoughts in teens. It targets adolescents aged 13-18 who have recently exhibited suicidal behavior and are already receiving standard mental health care. Participants will undergo treatments twice a week for the first two weeks, with regular check-ups continuing for up to 12 weeks. This double-blind study ensures unbiased results, as neither participants nor researchers know who receives which treatment. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

You may need to stop certain medications that affect how ketamine works in your body, especially those that change heart rate or blood pressure. ADHD medications should not be taken 24 hours before treatment. The study team will review your medications to see if any need to be stopped.

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

Research has shown that ketamine is generally safe and effective for quickly reducing suicidal thoughts. In a study with adults who had major depression, ketamine rapidly reduced these thoughts, and most participants tolerated the treatment well. Some reported side effects, such as feeling disconnected from reality and dizziness, but these effects were usually short-lived.

Studies have also indicated that midazolam, often used to help people relax, is generally safe. Common side effects include sleepiness and dizziness, but these are typically mild and temporary.

This trial tests both treatments to determine which better reduces suicidal thoughts in teenagers. The advanced stage of this trial suggests confidence in the safety of both treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for suicidal thoughts involve antidepressants or psychotherapy, which can take weeks to show effectiveness. But ketamine stands out because it has the potential to rapidly reduce suicidal thoughts, sometimes within hours. This fast-acting effect is due to ketamine's unique mechanism of action, which targets the brain's glutamate system rather than the serotonin system affected by most antidepressants. Researchers are excited about this treatment because it offers a new and faster way to help those in crisis, potentially saving lives by providing timely relief.

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

Research has shown that ketamine, one of the treatments under study in this trial, can quickly reduce suicidal thoughts in adults. One study found that two 40-minute IV doses significantly lowered these thoughts by the third day. Another study discovered that ketamine reduced suicidal thoughts within 24 hours. This trial compares ketamine to midazolam, a sedative often used for calming but not specifically for reducing suicidal thoughts. Overall, ketamine appears promising for quickly decreasing suicidal thoughts, making it a potential option for those in urgent need. ^{2 5 6 7 8}

Who Is on the Research Team?

Madhukar Trivedi, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

Adolescents aged 13-18 with recent suicidal behavior and a primary diagnosis of depression are eligible. They must be fluent in English, not have severe substance use issues or unstable medical conditions, and agree to use contraception. Those with certain psychiatric disorders or weighing over 120 kilograms are excluded.

Inclusion Criteria

You have had a serious suicidal event within the past month that required immediate evaluation or hospitalization.

I am receiving recommended mental health care.

My main diagnosis is depression.

Exclusion Criteria

My primary diagnosis is not depression.

Have unstable medical conditions (stable for less than 3 months) or with clinically significant laboratory values or an electrocardiogram (ECG) that would pose significant risk

You have been diagnosed with schizophrenia, a psychotic disorder, a developmental disorder, or mental retardation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either ketamine or midazolam infusions twice weekly for two weeks

2 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with weekly assessments

10 weeks

11 visits (combination of in-person and remote)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine Hydrochloride
• Midazolam Hydrochloride

Trial Overview The trial is testing the effectiveness of ketamine compared to midazolam in reducing suicidality among adolescents receiving standard care for depression. It's a double-blind study where treatments are given twice weekly initially, then assessed weekly up to week 12.

How Is the Trial Designed?

Group I: Midazolam Active Control 2 Interventions

0.02 mg/kg midazolam will be administered 4 times in a 2 week period. Midazolam will be dissolved in 0.9% sodium chloride in a total volume of 100ml and administered with a syringe infusion pump at a constant rate.

Group II: Ketamine Active Control 2 Interventions

0.5 mg/kg intravenous ketamine will be administered 4 times in a 2 week period. Ketamine will be dissolved in 0.9% sodium chloride in a total volume of 100ml and administered with a syringe infusion pump at a constant rate.

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?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

A review of four studies involving children in emergency departments found that both ketamine and midazolam provide similar efficacy and safety for conscious sedation.

Despite their comparable profiles, ketamine is favored by both parents and physicians, suggesting a preference for its use in pediatric sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midazolam or ketamine for procedural sedation of children in the emergency department. Munro, A., Machonochie, I.[2018]

A pilot study involving 16 participants with bipolar depression indicated that a sub-anesthetic dose of ketamine (0.5 mg/kg) may lead to a greater reduction in suicidal ideation compared to midazolam, with a mean difference of nearly 6 points on the Scale for Suicidal Ideation, although this was not statistically significant.

The study found promising correlations between memory improvement and reduction in suicidal thoughts after ketamine infusion, as well as a decrease in serum brain-derived neurotrophic factor (BDNF) associated with reduced suicidal ideation, suggesting potential biomarkers for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. Grunebaum, MF., Ellis, SP., Keilp, JG., et al.[2022]

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 study of 42 newly-diagnosed cancer patients, a single dose of ketamine significantly reduced suicidal ideation and overall depression levels compared to midazolam, with improvements noted as early as day 1 and continuing to day 3.

The findings highlight ketamine's potential as a rapid antidepressant for patients facing acute depression and suicidal thoughts, suggesting it may be an effective intervention in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine rapidly relieves acute suicidal ideation in cancer patients: a randomized controlled clinical trial. Fan, W., Yang, H., Sun, Y., 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 involving 60 healthy children aged 1.5 to 7 years, a combination of ketamine and midazolam was found to be the most effective pre-surgery sedation method, achieving 100% success in parental separation.

The ketamine and midazolam mixture also showed an 85% success rate for mask induction, significantly outperforming ketamine alone (42%) and midazolam alone (65%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine plus midazolam, a most effective paediatric oral premedicant. Warner, DL., Cabaret, J., Velling, D.[2022]

A systematic review of five randomized controlled trials involving 346 uncooperative children found that the combination of midazolam and ketamine was significantly more effective for sedation, achieving an 84% success rate compared to midazolam alone.

Children receiving the midazolam and ketamine combination exhibited calmer behavior (50%) compared to those receiving midazolam alone (37%), with only modest adverse effects that did not require special treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Evaluation of Ease of Dental Treatment and Clinical Efficiency of Midazolam vs Midazolam and Ketamine Combination for Sedation in Young Uncooperative Pediatric Patients: A Systematic Review. Rathi, GV., Padawe, D., Takate, V., et al.[2023]

In a study involving 151 participants from 10 clinical trials, it was found that the placebo response for suicidal ideation was greater than for other depressive symptoms when participants received saline or midazolam, suggesting that suicidal thoughts may respond differently to treatment than general depression symptoms.

These findings may help explain why intravenous ketamine shows rapid improvements in overall depressive symptoms but has more modest effects on suicidal ideation, indicating a need for further research into targeted treatments for suicidal thoughts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine. Bloomfield-Clagett, B., Ballard, ED., Greenstein, DK., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11823077/

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 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0165178124005675

Effect of intravenous ketamine on suicidality in adults with ... Mean C-SSRS score significantly decreased following a single ketamine infusion and was indicative of a reduction in suicidality from active to passive suicidal ...

3. 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 ...

4. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2017.17060647

Ketamine for Rapid Reduction of Suicidal Thoughts in ... Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06366334

NCT06366334 | Study of IV Ketamine for Emergency ... The study primary objective is to determine the feasibility of conducting a trial that investigates the efficacy of IV ketamine to reduce suicidal ideation in ...

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

The effect of a single dose of intravenous ketamine on ... Suicide is a public health crisis with limited treatment options. We conducted a systematic review and individual participant data meta-analysis examining ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04592809

Ketamine Versus Midazolam for Recurrence of Suicidality ... The study design is a double-blind, randomized, active-control trial of adolescents (ages 13-18 years) with recent suicidal behaviors (suicide attempt or ...