A Phase 3 interventional study of Ketamine and Midazolam in Major Depressive Episode, Unipolar Depression and Bipolar Depression, sponsored by University of Dublin, Trinity College. Completed at 1 site in Ireland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-13.
Sponsored by University of Dublin, Trinity College · Phase 3, Interventional, and Treatment
Pragmatic, randomised, controlled, parallel-group, superiority trial of ketamine vs. midazolam as an adjunctive therapy for depression. The main purpose of the trial is to assess the mood-rating score difference between ketamine and midazolam from before the first infusion to 24 hours after the final infusion, supplemented by a 95% confidence interval. There will also be a 24-week follow-up after the final infusion session.
Pragmatic, randomised, controlled, parallel-group, superiority trial. Trial participants will be patients admitted to St Patrick's University Hospital for treatment of a major depressive episode. The investigators aim to recruit up to 104 participants who will be eligible for this study and randomly allocate 52 patients to each group. Both participants and assessors will be blind to treatment allocation. Eligible consented participants will be randomly allocated in a 1:1 ratio to a course of up to eight infusions of either ketamine or midazolam twice weekly over up to four weeks. Block randomisation will be independently performed. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions. During the allocated infusions and follow-up period patients will be monitored for treatment-related adverse events relating to both mental and physical health. Participants will also be followed-up for 24 weeks after the end of the initial randomised treatment and assessment period lasting up to four weeks, in order to identify if and when relapse occurs. During the trial, both groups will continue usual inpatient care as prescribed by their treating team.
8,057 studies on the registry are indexed under Depression; 1,641 are open to participants now.
This study's enrollment of 63 is below the median of 84 across 6,720 interventional studies indexed under Depression.
Browse Depression studies →University of Dublin, Trinity College is the lead sponsor of 72 studies on the registry; 14 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants will receive up to a four-week course of twice-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
Drug: Ketamine
Participants will receive up to a four-week course of twice-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
Drug: Midazolam
A sub-anaesthetic dose of ketamine will be administered for up to a four-week course of twice-weekly infusions.
Also known as: Ketalar
A sub-anaesthetic dose of midazolam will be administered for up to a four-week course of twice-weekly infusions.
Also known as: Hypnovel
Montgomery Asberg Depression Rating Scale-10 item version (MADRS)
The MADRS is a validated, 10-item, observer-rated scale that measures the symptoms and severity of depression. The primary outcome measure will be the change from baseline in the MADRS score to 24 hours after the final infusion. MADRS will be completed at screening (prior to randomisation), before and after all infusion sessions (at the following timepoints: -40 (±20) mins before the infusion begins; +60 (±10) mins and +120 (±10) mins after the infusion begins; +24 (±1) hours after the infusion ends) and at the 6, 12 and 24 weeks follow-up time points. Sleep and appetite scores will be carried over from -40 minutes to +60 minutes, +120 minutes, and 24 hours after each infusion. Response to treatment is defined as a ≥50% improvement from baseline MADRS score. Remission is defined as achieving a MADRS score ≤10. For those deemed to be treatment remitters, relapse at follow-up time points is defined as a MADRS score of ≥18.
Time frame: 28 weeks
The Clinician-Administered Dissociative States Scale (CADSS)
The CADSS will measure dissociative symptoms, as a possible subjective side effect of either ketamine or midazolam. The CADSS consists of 23 items and scores for each item range from 0 to 4. The CADSS measures dissociative symptoms in the following domains: identity, proprioception, time perception, colour and depth perception, and other modalities. The maximum score is 92, with higher scores indicating more dissociative symptoms. The CADSS will be completed three times at each infusion session: before (-30 (±10) mins before the infusion begins), during (+30 (±5) mins after the infusion begins) and after (+60 (±10) mins after the infusion begins, i.e. 20 (±10) mins after the infusion ends).
Time frame: 4 weeks
The Brief Psychiatric Rating Scale (BPRS)
The positive symptoms subscale of the BPRS will be used to measure psychotomimetic effects of either ketamine or midazolam. This 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each item is scored between 0 and 7. The maximum score is 28, with higher scores indicating more severe psychotic symptom. Participants will complete the BPRS three times at each infusion session: before (-30 (±10) mins before the infusion begins), during (+30 (±5) mins after the infusion begins) and after (+60 (±10) mins after the infusion begins, i.e. 20 (±10) mins after the infusion ends).
Time frame: 4 weeks
Young Mania Rating Scale (YMRS; mood item)
The YMRS is an observer-rated assessment tool for severity of mania and hypomania. The single mood item of the YMRS, rated from 0 to 4 (representing a range from normal mood to frank euphoria), will be used to assess for possible mood elevation during the infusion sessions. Higher scores reflect more elevated mood. Participants will have the YMRS performed three times at each infusion session: before (-30 (±10) mins before the infusion begins), during (+30 (±5) mins after the infusion begins) and after (+60 (±10) mins after the infusion begins, i.e. 20 (±10) mins after the infusion ends).
Time frame: 4 week
Observer's Assessment of Alertness/Sedation; responsiveness subscale (OAA/S-R)
The OAA/S-R is an observer-rated assessment that will be used to measure levels of sedation experienced by participants during either ketamine or midazolam infusion. The OAA/S-R ranges in score from 1 to 5, where 1 denotes deep sleep (i.e. no response to mild prodding or shaking) and 5 denotes fully alert. The OAA/S-R will be completed three times at each infusion session: before (-30 (±10) mins before the infusion begins), during (+30 (±5) mins after the infusion begins) and after (+60 (±10) mins after the infusion begins, i.e. 20 (±10) mins after the infusion ends).
Time frame: 4 weeks
20-item Physician Withdrawal Checklist (PWC-20)
The PWC-20 will be used to assess for potential withdrawal symptoms during and after completion of the allocated course of ketamine/midazolam infusions. The PWC-20 is a brief checklist and each item is rated from 0 (not present) to 3 (severe). PWC-20 scores range from 0 to 60, with higher scores indicating more withdrawal symptoms with greater severity. The PWC-20 will be completed at screening (prior to randomisation), 24 (±1) hours after the end of the fourth and final infusions, and the 6- and 12-week follow-up timepoints.
Time frame: 16 weeks
The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR)
The QIDS-SR is a validated, self-report measure of depressive symptoms. The QIDS-SR consists of 16 items, with each item rated on a scale from 0 to 3. Total scores range from 0 to 48, with higher scores reflecting greater burden of depressive symptoms. The QIDS-SR will be completed at screening (prior to randomisation), before and after all infusion sessions (at the following timepoints: -40 (±20) mins before the infusion begins; +60 (±10) mins and +120 (±10) mins after the infusion begins; +24 (±1) hours after the infusion ends) and at the 6, 12 and 24 weeks follow-up time points. Sleep and appetite items 1,2,3,4,6,7,8 \& 9 on the QIDS-SR will be carried over from -40 minutes before each infusion to +60 minutes, +120 minutes \& 24 hours after each infusion in line with the methodology of previous literature.
Time frame: 28 weeks
Patient-Rated Inventory of Side Effects (PRISE)
The PRISE is a 9-item, self-report measure that will document general adverse events experienced by patients during each infusion, by identifying and evaluating the tolerability of each adverse event. The PRISE assesses adverse events in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rate whether or not the symptoms are tolerable or distressing. The PRISE will be completed at screening (prior to randomisation), after all infusion sessions (+120 (±10) mins after the infusion begins), and at the 6, 12 and 24 weeks follow-up time points.
Time frame: 28 weeks
The Montreal Cognitive Assessment (MoCA)
The MoCA is a rapid screening instrument for mild cognitive dysfunction. It assesses the following cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. The maximum score is 30, with higher scores indicating better cognition. The MoCA will be completed at screening (prior to randomisation), at +120 (±10) mins after the infusion begins during the first and final infusion sessions, and at the 12 and 24 weeks follow-up time points.
Time frame: 28 weeks
EuroQol-5 dimensions-5 level scale for health status (EQ-5D-5L)
Health-related quality-of-life will be measured using the EQ-5D-5L. The EQ-5D-5L consists of the EQ-5D descriptive system, and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system includes the following five dimensions that assess an individual's self-rated health status: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is rated on a 5-point Likert scale. The digits related to each response to the five dimensions are combined into a 5-digit number, which describes the patient's health state. The EQ VAS includes a vertical visual analogue as a quantitative measure of subjectively rated health, with endpoints labelled as 'Best imaginable health status' and 'Worst imaginable health status'. The EQ-5D-5L will be administered at screening (prior to randomisation) and at the 6-, 12- and 24-week follow up time periods.
Time frame: 28 weeks
Client Service Receipt Inventory (CSRI)
The CSRI will calculate healthcare costs using the following data: sociodemographic information, usual living situation, employment status and income levels and the care services and supports used by participants. Currently prescribed medicines will also be recorded. Healthcare costs will be estimated using the CSRI at baseline and at the 6-, 12- and 24-week follow-up timepoints.
Time frame: 28 weeks
Adverse events (AE) and serious adverse events (SAE) review
AEs and SAEs will be reviewed at every visit. All AEs and SAEs will be reported and followed up until resolved or until final visit.
Time frame: 28 weeks
Concomitant Medication
All medications taken one month prior to participant screening will be recorded. At all other visits, concomitant medication taken since last visit will be documented. Adherence to prohibited/contraindicated medication requirements will be assessed and documented at each infusion visit.
Time frame: 28 weeks
Plan to share: No
This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Dublin, Trinity College