Ketamine as an Adjunctive Therapy for Major Depression - a Randomised Controlled Pilot Trial: The KARMA-Dep Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)
Study Overview
Brief Summary
Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam as an adjunctive therapy for depression. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.
Detailed Description
Pragmatic, randomised, controlled, parallel-group, pilot trial. Trial participants will be patients admitted to St Patrick's University Hospital for treatment of a depressive episode. The investigators aim to recruit up to 20 participants who will be eligible for this study and randomly allocate 10 patients to each group. The participants will undergo usual inpatient care as prescribed by their treating team for the index acute depressive episode. Both participants and assessors will be blind to treatment allocation. Consented participants will be randomly allocated in a 1:1 ratio to a four week course of either once-weekly ketamine or midazolam infusions. Block randomisation will be independently performed. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions. Blood samples will be taken at four time-points in the first infusion session and before the final infusion for neuroplasticity biomarker studies. Both groups will continue treatment as usual. Participates will also be followed up over a three month period.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •≥18 years old
- •Hamilton Rating Scale for Depression-24 item version (HRSD-24) score of ≥21
- •Voluntary admission for treatment of an acute depressive episode
- •Meet Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-V) criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)
Exclusion Criteria
- •Current involuntary admission
- •Medical condition rendering unfit for ketamine/midazolam
- •Active suicidal intention
- •History of Axis 1 diagnosis other than major depression
- •Electroconvulsive Therapy (ECT) administered within the last two months
- •Alcohol/substance dependence in previous six-months
- •Pregnancy or inability to confirm use of adequate contraception during the trial
- •Breastfeeding women
Arms & Interventions
Ketamine
Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
Intervention: Ketamine (Drug)
Midazolam
Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
Intervention: Midazolam (Drug)
Outcomes
Primary Outcomes
The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)
Time Frame: 15 weeks
The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms. Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later. Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.
Secondary Outcomes
- The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)(15 weeks)
- The Clinician-Administered Dissociative States Scale (CADSS)(4 weeks)
- The Brief Psychiatric Rating Scale (BPRS)(4 weeks)
- Young Mania Rating Scale (YMRS; Mood Item)(4 weeks)
- The Patient-Rated Inventory of Side Effects (PRISE)(4 weeks)
- The Montreal Cognitive Assessment (MoCA)(15 weeks)
Investigators
Prof Declan McLoughlin
Professor
St Patrick's Hospital, Ireland