Ketamine + Midazolam for Depression
(UNIKET Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Texas Southwestern Medical Center
Must not be taking: Antidepressants, Antipsychotics, Benzodiazepines, others
Disqualifiers: Schizophrenia, Bipolar, Substance use, others
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?The study is investigating dysfunctions in neurocircuitry in regards to irritability with healthy controls (HC) and individuals with Major Depressive Disorder (MDD) by performing MRIs. The MDD group will also be randomized to receive ketamine or midazolam to investigate changes post-treatment in neurocircuitry with regards to irritability.
Do I need to stop my current medications to join the trial?
You must either be free of certain medications like antidepressants and antipsychotics or be stable on them for four weeks before the trial starts.
What data supports the effectiveness of the drug combination of ketamine and midazolam for depression?
Research shows that the combination of ketamine and midazolam is effective in managing pain and sedation in children, suggesting it may have potential benefits for depression treatment due to its calming and pain-relieving effects.
12345Is the combination of ketamine and midazolam safe for use in humans?
Research shows that the combination of ketamine and midazolam is generally safe for use in humans, particularly in children undergoing pain procedures, with no major complications observed. Some minor side effects like nausea, vomiting, and salivation were noted, but overall, the combination was well-tolerated.
26789How is the drug Ketamine + Midazolam unique for treating depression?
The combination of Ketamine and Midazolam is unique for treating depression because Ketamine acts rapidly to relieve symptoms, including suicidal thoughts, which is different from traditional antidepressants that often take weeks to work. Additionally, the use of Midazolam, a benzodiazepine, may help manage anxiety and enhance the sedative effects, making the treatment potentially more effective for immediate relief.
12101112Eligibility Criteria
This trial is for adults aged 18-65 with Major Depressive Disorder (MDD) who can undergo MRI scans and are willing to receive ketamine or midazolam infusions. Healthy controls without psychiatric conditions can also participate. All must understand English, not be on certain medications, agree to use contraception, and not have a high risk of substance abuse or suicidal behavior.Inclusion Criteria
I agree to use birth control during the study and for 3 months after.
I am between 18 and 65 years old and weigh 120 kg or less.
I haven't taken any psychotropic or certain anticonvulsant medications, or have been stable on them for 4 weeks.
+5 more
Exclusion Criteria
I am not taking any medications that are not allowed in the study.
I do not have any unstable illnesses affecting my organs or immune system.
Any claustrophobia or other conditions which may result in inability to lie still in the MRI scanner for 1 hour or more
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Participants undergo baseline assessments including pre-treatment fMRI scans
1 week
1 visit (in-person)
Treatment
MDD participants receive twice-weekly intravenous infusions of either ketamine or midazolam for 2 weeks
2 weeks
4 visits (in-person)
Post-Treatment Assessment
Clinical assessments and fMRI scans are repeated after the last infusion
1 week
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study examines brain function related to irritability in people with MDD using MRIs before and after administering either ketamine or midazolam. It aims to identify how these treatments affect the neurocircuitry associated with irritability compared to healthy individuals.
3Treatment groups
Active Control
Placebo Group
Group I: Healthy ControlsActive Control1 Intervention
Healthy controls will undergo clinician assessments and fMRI to compare to MDD group.
Group II: MDD - KetamineActive Control1 Intervention
Participants with MDD who have completed all baseline assessments including pre-treatment fMRI scan randomly allocated to receive four ketamine infusions.
Group III: MDD - MidazolamPlacebo Group1 Intervention
Participants with MDD who have completed all baseline assessments including pre-treatment fMRI scan randomly allocated to receive four midazolam infusions.
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
References
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.
Use of intravenous ketamine-midazolam association for pain procedures in children with cancer. A prospective study. [2022]We evaluated the safety and efficacy of midazolam-ketamine association to control pain induced by diagnostic procedures in paediatric oncology patients. 226 procedures were carried out in 92 patients aged three days to 18 years. Drugs were given i.v. by an anaesthesiologist. Midazolam dose was 25 microg.kg-1 and ketamine 0. 5 to 2 mg.kg-1, depending on number and invasiveness of procedures. The mean dose of ketamine was 1 mg.kg-1. Mean duration of sedation was ten min. No complication was observed and analgesia was considered satisfactory in 89 out of 92 patients. These results indicate that midazolam-ketamine is a safe and effective association in pain management for paediatric oncology patients and efficiently induces brief unconscious sedation with analgesia.
A double-blind, randomised, placebo-controlled trial of oral midazolam plus oral ketamine for sedation of children during laceration repair. [2022]To compare the efficacy of oral midazolam alone with a combination of oral midazolam and ketamine in children requiring laceration repair.
Comparative evaluation of midazolam and ketamine with midazolam alone as oral premedication. [2022]Oral premedication with midazolam and ketamine is widely used in pediatric anesthesia to reduce emotional trauma and ensure smooth induction. However, various dosing regimens when used alone or in combination have variable efficacy and side effect profile. The aim of our study was to investigate and compare the efficacy of oral midazolam alone with a low-dose combination of oral midazolam and ketamine.
Midazolam with ketamine: Who benefits? [2017][Kennedy RM, McAllister JD. Midazolam with ketamine: who benefits? Ann Emerg Med . March 2000;35:297-299.].
A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. [2022]Several studies now provide evidence of ketamine hydrochloride's ability to produce rapid and robust antidepressant effects in patients with mood and anxiety disorders that were previously resistant to treatment. Despite the relatively small sample sizes, lack of longer-term data on efficacy, and limited data on safety provided by these studies, they have led to increased use of ketamine as an off-label treatment for mood and other psychiatric disorders.
Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. [2013]Narrative review of the literature on the efficacy and safety of subanaesthetic doses of ketamine for the treatment of depression.
The use of midazolam in diagnostic and short surgical procedures in children. [2019]A new technique of sedation for children is described, in which midazolam (0.2 mg.kg-1) was administered topically by the nasal route, followed by ketamine (9.0 mg.kg-1) administered rectally in 32 patients breathing air spontaneously. Sedation was good in 23, seven required further ketamine (1.0 mg.kg-1 i.v.), and in two, halothane was introduced. There was no evidence of severe respiratory depression except during oesophagoscopy. Cardiovascular stability was excellent. Of 21 patients over 5 years old, 19 developed complete and two partial anterograde amnesia for the administration of ketamine and surgery. The major complications were nausea and vomiting (five patients) and salivation (eight patients). The mean recovery time was 40 min (s.d. 33 min). It provided a relatively safe, adaptable, non-invasive method of inducing sedation in children.
Subcutaneous ketamine infusion in palliative patients for major depressive disorder (SKIPMDD)-Phase II single-arm open-label feasibility study. [2023]Ketamine at subanaesthetic dosages (≤0.5mg/kg) exhibits rapid onset (over hours to days) antidepressant effects against major depressive disorder in people who are otherwise well. However, its safety, tolerability and efficacy are not known for major depressive disorder in people with advanced life-limiting illnesses.
Low- versus high-dose combination of midazolam-ketamine for oral premedication in children for ophthalmologic surgeries. [2022]Midazolam and ketamine are useful for oral premedication in children to allay anxiety. We compared the effects of midazolam with a combination of high- and low-dose ketaminemidazolam as an oral premedication.
Effect of Concomitant Benzodiazepines on the Antidepressant Effects of Ketamine: Findings From the RAPID Intravenous Ketamine Study. [2022]Objective: Ketamine is a novel and rapidly acting treatment for major depressive disorder (MDD). Benzodiazepines are commonly coprescribed with antidepressants in MDD. This study sought to examine data from a randomized clinical trial that compared a single infusion of intravenous (IV) ketamine to midazolam placebo in treatment-resistant depression (DSM-IV-TR MDD) and to assess whether the use of concomitant oral benzodiazepines differentially affected treatment response to ketamine versus midazolam.
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.