Ketamine vs Midazolam for Suicidal Thoughts
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This project aims to examine the efficacy of ketamine, a rapidly acting medication shown to decrease suicidality in adults in as short as hours or days, as opposed to weeks.
The study design is a double-blind, randomized, active-control trial of adolescents (ages 13-18 years) with recent suicidal behaviors (suicide attempt or increased suicidal ideation). All participants must be receiving standard of care treatment which may range broadly from both outpatient and inpatient programs which include clinically indicated psychosocial and/or psychopharmacological treatments. Ketamine/midazolam treatment will occur twice weekly during the first two weeks of the study, followed by weekly assessments through week 12.
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.
What data supports the effectiveness of the drug ketamine for reducing suicidal thoughts?
Research shows that ketamine can quickly reduce suicidal thoughts, with effects appearing within an hour and lasting up to a week. Studies have found that ketamine is more effective than midazolam in reducing suicidal thoughts in patients with depression and cancer.
12345Is ketamine or midazolam safe for treating suicidal thoughts?
Both ketamine and midazolam have been studied for safety in various conditions, including sedation in children and treatment of depression with suicidal thoughts. Research suggests that both drugs have similar safety profiles, but ketamine is often preferred due to its rapid effects on reducing suicidal thoughts.
13456How is ketamine different from other drugs for treating suicidal thoughts?
Ketamine is unique because it can rapidly reduce suicidal thoughts and overall depression levels, often within a day, which is faster than many traditional antidepressants. It is administered in a sub-anesthetic dose intravenously (through a vein), and its quick action makes it particularly novel for acute situations.
34578Eligibility Criteria
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.
+3 more
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.
+7 more
Trial Timeline
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)
Participant Groups
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.
2Treatment groups
Active Control
Group I: MidazolamActive Control2 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: KetamineActive Control2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UT Southwestern Medical CenterDallas, TX
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Who Is Running the Clinical Trial?
University of Texas Southwestern Medical CenterLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible Use as Crisis Intervention in Patients at Suicide Risk. [2022]A growing body of literature suggests that ketamine, administered in subanesthetic doses, has early-onset antidepressant action in patients with severe and even treatment-refractory depression. Many case reports, open-label studies, and randomized controlled trials (RCTs) suggest that ketamine may have dramatic antisuicidal effects, as well. This article examines the benefits of ketamine in patients with suicidal ideation with particular focus on the findings of recent RCTs and meta-analyses. Important findings are that a single dose of ketamine is associated with antisuicidal benefits that emerge within an hour of administration and persist for up to a week. The benefits are seen in patients with mild as well as clinically significant suicidal ideation. The benefits are observed in midazolam- as well as saline-controlled trials. Effect sizes are medium to large. The improvement in suicidal ideation is only partly explained by improvement in depression severity. It is concluded that there is consistent evidence that a single dose of ketamine has dramatic antisuicidal action that emerges almost immediately after dosing and persists for at least a week. The short- and intermediate-term safety and efficacy of ketamine as a crisis intervention treatment for suicidal patients merit study. Areas that need research are outlined.
Clinical predictive factors and trajectories of suicidal remission over 6 weeks following intravenous ketamine for suicidal ideation. [2023]Ketamine is efficient for short-term reduction of suicidal ideas. Predictive factors and outcome trajectories are poorly characterized.
Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. [2022]To evaluate feasibility and effects of a sub-anesthetic infusion dose of ketamine versus midazolam on suicidal ideation in bipolar depression. Neurocognitive, blood and saliva biomarkers were explored.
Ketamine rapidly relieves acute suicidal ideation in cancer patients: a randomized controlled clinical trial. [2022]This study was designed to examine the rapid antidepressant effects of single dose ketamine on suicidal ideation and overall depression level in patients with newly-diagnosed cancer. Forty-two patients were enrolled into the controlled trial and randomized into two groups: ketamine group and midazolam group. Patients from the two groups received a sub-anesthetic dose of racemic ketamine hydrochloride or midazolam. Suicidal ideation score, measured with the Beck Scale and suicidal part of the Montgomery-Asberg Depression Rating Scale, significantly decreased on day 1 and day 3 in ketamine-treated patients when compared to those treated with midazolam. Consistently, overall depression levels measured using the Montgomery-Asberg Depression Rating Scale indicated a significant relief of overall depression on day 1 in ketamine-treated patients. Collectively, this study provides novel information about the rapid antidepressant effect of ketamine on acute depression and suicidal ideation in newly-diagnosed cancer patients.
A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine. [2023]Clinical trials of intravenous (IV) racemic (R,S)-ketamine (hereafter referred to as IV ketamine) have consistently reported rapid and substantial reductions in overall depressive symptoms compared with saline (inactive placebo) or midazolam (active placebo). The evidence for IV ketamine's specific effects on suicidal ideation is less clear, however. This study sought to examine whether differential placebo (saline or midazolam) response to overall depressive symptoms vs suicidal ideation may help explain these divergent findings.
Midazolam or ketamine for procedural sedation of children in the emergency department. [2018]A short cut review was carried out to establish whether ketamine or midazolam is superior at providing safe and effective conscious sedation in children in the emergency department. A total of 203 papers were found using the reported searches, of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are summarised in table 1. It is concluded that midazolam and ketamine have similar efficacy and safety profiles but that ketamine is preferred by parents and physicians.
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. [2023]To assess and compare the effectiveness of midazolam vs midazolam and ketamine combination in the management of young uncooperative pediatric patients.
Ketamine plus midazolam, a most effective paediatric oral premedicant. [2022]Healthy children, 1.5 to seven years old, were divided into three groups of 20 each. Group 1 received midazolam 0.5 mg.kg-1, Group 2, ketamine 6 mg.kg-1 and Group 3 a mixture of midazolam 0.4 mg.kg-1 + ketamine 4 mg.kg-1. Each dose was mixed with atropine 0.02 mg.kg-1 plus an equal volume of cherry syrup and was given orally 20 to 30 min prior to surgery. A grade of 1 (asleep, difficult to arouse), 2 (asleep, easily aroused), 3 (awake, calm), 4 (awake, anxious, occasional cry), or 5 (crying, agitated), was assigned at the time of parental separation and again when mask induction was begun. A grade of 1-3 was considered successful. For parental separation, the mixture of ketamine+midazolam was 100% successful, ketamine 90% and midazolam 75%. Successful mask induction for the mixture of ketamine+midazolam was 85%, midazolam 65% and ketamine 42%. This study indicates that a mixture of ketamine+midazolam is the most effective.