Clinical trial NCT04082858: Ketamine Interleaved With Electroconvulsive Therapy for Depression
Official title: Ketamine Interleaved With Electroconvulsive Therapy for Depression, A Pragmatic Randomised Controlled Pilot Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Depression
Keywords: Ketamine
Electroconvulsive Therapy
Depression
ECT
Lead sponsor: St Patrick's Hospital, Ireland
Sponsor class: OTHER
First posted: 2019-09-09
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic, randomised, controlled, parallel group, pilot clinical trial
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Pragmatic, randomised, controlled, parallel group, pilot clinical trial of ketamine vs. midazolam interleaved with electroconvulsive therapy (ECT) as an adjunctive treatment for a major depressive episode. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.

Detailed description: Patients referred for treatment with ECT at St Patrick's Mental Health Services for treatment of a depressive episode will be eligible for recruitment to the clinical trial. Participants will be invited to be randomised to a course of twice-weekly ketamine or midazolam infusions for the duration of ECT. Participants will receive the first allocated infusion following the first or second treatment with ECT. Block randomisation will be independently performed. Infusions will be delivered on separate days to ECT. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions.Treatment-as-usual will continue throughout the entire trial.

Trial Interventions: participants will receive twice-weekly infusions of either ketamine at 0.5mg/Kg or midazolam at 0.045mg/Kg. All infusions will be administered by a Consultant Anaesthetist. Repeated infusions of allocated drug have been shown to be safe and well tolerated by patients with mental illness. Minor haemodynamic changes and psychotomimetic side effects can occur and will be assessed regularly during infusions and for 120 minutes afterwards. Participants will be followed-up at six weeks and three months after the final infusion to assess for relapse according to standardised criteria.

Eligibility criteria: Inclusion Criteria:

* ≥18 years old
* Able to provide informed consent
* Voluntary admission for treatment of an acute depressive episode
* Meet DSM-V criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)
* Montgomery Asberg Depression Rating Scale 10 item version (MADRS) score of ≥20
* Referred for treatment with ECT
* Sufficiently physically healthy to receive ketamine/midazolam and ECT

Exclusion Criteria:

* Inability to provide informed consent
* Current involuntary admission
* History of Axis 1 diagnosis other than major depression
* Medical condition rendering unfit for ECT
* Active suicidal intention
* Presence of major neurological or organic brain disorder
* Alcohol/substance dependence in previous six-months
* Pregnancy or inability to confirm use of adequate contraception during the trial
* Breastfeeding women
* Contraindications to ketamine
* Contraindications to midazolam

Primary outcomes:
measure: Montgomery Asberg Depression Rating Scale (MADRS)
timeFrame: 18 weeks
Secondary outcomes:
measure: The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR16)
timeFrame: 18 weeks
measure: The Clinician-Administered Dissociative States Scale (CADSS)
timeFrame: 6 weeks
measure: The Brief Psychiatric Rating Scale (BPRS)
timeFrame: 6 weeks
measure: Young Mania Rating Scale (YMRS; mood item)
timeFrame: 6 weeks
measure: The Patient-Rated Inventory of Side Effects (PRISE)
timeFrame: 6 weeks
measure: The Montreal Cognitive Assessment (MoCA)
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: St Patrick's University Hospital
state: Co. Dublin
Study officials:
affiliation: St Patrick's Hospital
name: Declan McLoughlin, PhD
role: PRINCIPAL_INVESTIGATOR
References: