Ketamine for Depression Relapse Prevention Following ECT

NCT02414932 | Completed Early Phase 1 Results DMC

• 2 other identifiers: SPUH 05/142014-004262-14
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Depression affects up to 20% of people in their lifetime and can be a severe debilitating illness. Indeed, the World Health Organisation has estimated that depression will soon be the second leading contributor to the burden of disease worldwide. One of the big problems for patients and doctors is that currently available antidepressant drugs and psychotherapies do not work for 30% of people. However, about 60% of such treatment-resistant patients will recover fully with electroconvulsive therapy (ECT). Even though it was developed over 75 years ago, ECT continues to be the most powerful treatment for severe, often life-threatening, depression. Despite that, we have recently reported that severe depression symptoms return (called a "relapse") in nearly 40% of such responders within six months of completing a course of ECT. Actually, such high relapse rates are seen for all patients with treatment-resistant depression, irrespective of what treatment they have received. There is thus an urgent need for better treatments to prevent relapse and one such possibility is an old drug called ketamine. Ketamine blocks the activity of glutamate, one of the major chemical messenger systems in the brain. Because of this effect it is sometimes used as an anaesthetic but it can also make you feel a bit "high" and so is sometimes abused as a recreational drug. Fortunately, in small doses it is quite safe. Recently, it has been found that ketamine has a remarkably rapid, but brief, antidepressant effect, including reducing suicidal thoughts. We wish to evaluate ketamine as a way to reduce relapse rates in people who have just been treated successfully with ECT for severe depression. Developing such a new treatment, and understanding how it works, would be of tremendous benefit to persons with severe depression, their families, and the wider society.

Conditions

Depression

Keywords

ketamine; electroconvulsive therapy; glutamate

Outcome Measures

Primary Outcomes (1)

• Completion Rate for Randomised Treatment

  Process outcomes are primary in this pilot trial. These include recruitment methods and rate of completion and will be assessed following the completion of the trial

  30 months

Secondary Outcomes (1)

• Depression Relapse Rate

  6 months

Study Arms (2)

Ketamine

EXPERIMENTAL

Ketamine (ketamine hydrochloride 0.5 mg/kg; Pfizer Healthcare Ireland)) will be made up as a 50 ml colourless saline solution and administered as a slow infusion over 40 minutes using an intravenous infusion pump. A course of up to four once-weekly infusions will be administered. Infusions will be discontinued by the Anaesthetist if there are persisting haemodynamic changes (i.e. heart rate \>110/minute or systolic/diastolic blood pressure (BP) \>180/100 or \>20% increase above pre-infusion BP for more than 15 minutes) that do not respond to beta-blocker therapy.

Drug: Ketamine

Midazolam

ACTIVE COMPARATOR

Midazolam (0.045 mg/kg; Roche Products Ireland Ltd) will be made up as a 50 ml colourless saline solution and administered as a slow infusion over 40 minutes using an intravenous infusion pump. A course of up to four once-weekly infusions will be administered.

Drug: Midazolam

Interventions

Ketamine DRUG

Ketamine hydrochloride 0.5 mg/kg; Pfizer Healthcare Ireland

Also known as: Ketalar

Ketamine

Midazolam DRUG

Midazolam 0.045 mg/kg; Roche Products Ireland Ltd

Also known as: Hypnovel

Midazolam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥18 years with unipolar major depressive disorder (DSM-IV)
• item Hamilton Rating Scale for Depression (HRSD-24) score of ≥21
• Referred for ECT
• For the randomised Phase 2, patients must have
• received a substantial course of ECT in Phase 1 (i.e. at least five sessions)
• achieved at least response criteria (i.e. ≥60% decrease from baseline HRSD-24 score and score ≤16 on two consecutive weekly ratings)
• have a nominated adult who can stay with them for 24-hours on out-patient treatment days
• Mini-Mental State Examination (MMSE) score of ≥24
• able to provide informed consent

You may not qualify if:

• Any condition rendering patient medically unfit for ECT; general anaesthesia, ketamine or midazolam - assessed by physical examination, routine haematology and biochemistry investigations prior to enrolment in Phase I (routine care)
• Active suicidal intention
• Dementia, intellectual disability, or MMSE \<24
• Lifetime history of bipolar affective disorder
• Current history of post-traumatic stress disorder
• Other Axis I diagnosis (DSM-IV)
• ECT in the six months prior to recruitment
• Alcohol dependence or substance misuse in the six months prior to recruitment
• Pregnancy or breast-feeding
• Residing in a nursing home
• Prisoner
• Diagnosis of terminal illness
• Inability or refusal to provide valid informed consent

Sponsors & Collaborators

• St Patrick's Hospital, Ireland: lead
• Health Research Board, Ireland: collaborator

Study Sites (1)

St Patrick's University Hospital

Dublin, 8, Ireland

Location

Related Publications (1)

• Finnegan M, Ryan K, Shanahan E, Harkin A, Daly L, McLoughlin DM. Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial). Pilot Feasibility Stud. 2016 Aug 3;2:38. doi: 10.1186/s40814-016-0080-0. eCollection 2016.

  PMID: 27965856 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Recruitment and randomisation rates in this pilot trial were low, leading to small participant numbers analysed. Due to the potential for breach of confidentiality, limited participant-level information has been reported.

Results Point of Contact

• Title: Dr Martha Finnegan
• Organization: Trinity College Dublin

mfinneg@tcd.ie

0035312493385

Study Officials

• Declan M McLoughlin

  St Patrick's Hospital/Trinity College

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 8, 2015
• First Posted: April 13, 2015
• Study Start: April 1, 2015
• Primary Completion: April 7, 2017
• Study Completion: April 7, 2017
• Last Updated: May 6, 2021
• Results First Posted: May 6, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)