Enhancing the Effectiveness of Electroconvulsive Therapy in Severe Depression

NCT01907217 | Completed Phase 4 Results DMC

• 2 other identifiers: TRA/2007/5ISRCTN23577151
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

Electroconvulsive therapy (ECT) is the most powerful antidepressant treatment available and is often life-saving. There are concerns, however, that standard bitemporal ECT (the most commonly used form of ECT worldwide) causes persisting retrograde amnesia. However, clinical trials have indicated that high-dose unilateral ECT may be as effective as bitemporal ECT but have much less cognitive side-effects. The trial aims to test the primary experimental hypothesis: High-dose (6 x ST) right unilateral ECT is as effective as (i.e. not inferior to) standard (1.5 x ST) bitemporal ECT for severe depression in terms of Hamilton Depression Rating Score (HDRS) at the end of the treatment course.

Conditions

Depression

Keywords

Electroconvulsive therapy; ECT; electrode placement; effectiveness; cognition; autobiographical memory

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Rating Scale (HDRS)

  The HDRS was originally designed to assess severity of depressive symptoms in patients with a primary depressive illness and is now the most commonly used measure of depression severity. It was first published in 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 HDRS includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.

  HDRS scores were obtained at baseline, end of allocated ECT treatment, and at 3 and 6 month follow-up timepoints.

Secondary Outcomes (3)

• Columbia Autobiographical Memory Interview-Short Form (AMI-SF)

  end of allocated ECT course

• Columbia Autobiographical Memory Interview-Short Form (AMI-SF)

  3 months follow-up

• Columbia Autobiographical Memory Interview-Short Form (AMI-SF)

  6 months follow-up

Study Arms (2)

Bilateral ECT Mecta 5000M

ACTIVE COMPARATOR

Modified bilateral ECT (bitemporal electrode positions) twice weekly at 1.5 times the seizure threshold. Methohexitone (0.75-1.0 mg/kg) is used for anaesthesia with suxamethonium (0.5-1.0mg/kg) for muscle relaxation.

Device: ECT Mecta 5000M; Drug: Methohexitone; Drug: Suxamethonium

High-dose unilateral ECT Mecta 5000M

EXPERIMENTAL

High-dose right modified unilateral ECT twice weekly at 6 times the seizure threshold. Methohexitone (0.75-1.0 mg/kg) is used for anaesthesia with suxamethonium (0.5-1.0mg/kg) for muscle relaxation.

Device: ECT Mecta 5000M; Drug: Methohexitone; Drug: Suxamethonium

Interventions

ECT Mecta 5000M DEVICE

ECT is administered twice weekly with hand-held electrodes using the Mecta 5000M device following a standard stimulus dosing protocol. Seizure duration is measured by EEG monitoring. Methohexitone (0.75-1.0 mg/kg) is used for anaesthesia with suxamethonium (0.5-1.0 mg/kg) as muscle relaxant. Seizure threshold (ST) is established by a method of limits at the first session and subsequent treatments will be given at 1.5 x ST for BT ECT and 6.0 x ST for RUL ECT. To reflect routine clinical practice, number of ECT treatments is determined by referring physicians who will be blind to randomisation. The treatment period varies between patients to allow up to 12 administrations of ECT, i.e. up to 6 weeks.

Also known as: electroconvulsive therapy Mecta 500M device

Bilateral ECT Mecta 5000M; High-dose unilateral ECT Mecta 5000M

Methohexitone DRUG

Methohexitone (0.75-1.0 mg/kg) is used for anaesthesia along with suxamethonium (0.5-1.0 mg/kg)for muscle relaxation. Anesthesia is the same for both arms of the trial.

Also known as: methohexital, Brevimytal (Hikma, Germany)

Bilateral ECT Mecta 5000M; High-dose unilateral ECT Mecta 5000M

Suxamethonium DRUG

Suxamethonium (0.5-1.0 mg/kg)is used for muscle relaxation along with Methohexitone (0.75-1.0 mg/kg) for anaesthesia. Anesthesia is the same for both arms of the trial.

Also known as: Succinylcholine, Anectine (GlaxoSmithKline, UK)

Bilateral ECT Mecta 5000M; High-dose unilateral ECT Mecta 5000M

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 diagnosed with major depressive episode (DSM-IV) and referred for ECT

You may not qualify if:

• Any condition rendering patients medically unfit for general anaesthesia or ECT; treatment with ECT in previous six months; dementia or other Axis 1 diagnosis; alcohol/other substance abuse in previous six months; inability/refusal to 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)

• Fenton C, McLoughlin DM. Usefulness of Hamilton rating scale for depression subset scales and full versions for electroconvulsive therapy. PLoS One. 2021 Nov 9;16(11):e0259861. doi: 10.1371/journal.pone.0259861. eCollection 2021.

  PMID: 34752484 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Methohexital; Succinylcholine; halofantrine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Barbiturates; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Choline; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Succinates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Onium Compounds

Limitations and Caveats

We did not include involuntary patients who could not consent due to illness severity (7.4% of referrals), for whom bitemporal ECT may be better. The AMI-SF does not allow quantification of retrograde amnesia attributable directly to ECT.

Results Point of Contact

• Title: Prof Declan McLoughlin
• Organization: St Patrick's University Hospital

d.mcloughlin@tcd.ie

+353 1 2493343

Study Officials

• Declan M McLoughlin, PhD

  St Patrick's University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 16, 2013
• First Posted: July 24, 2013
• Study Start: May 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: April 1, 2015
• Last Updated: November 14, 2018
• Results First Posted: November 14, 2018

Record last verified: 2018-04

Locations

IE (1)