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Enhancing the Effectiveness of Electroconvulsive Therapy in Severe Depression (EFFECT-Dep)

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ClinicalTrials.gov Identifier: NCT01907217
Recruitment Status : Completed
First Posted : July 24, 2013
Results First Posted : November 14, 2018
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
Health Research Board, Ireland
Information provided by (Responsible Party):
Prof Declan McLoughlin, St Patrick's Hospital, Ireland

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.


Condition or disease Intervention/treatment Phase
Depression Device: ECT Mecta 5000M Drug: Methohexitone Drug: Suxamethonium Phase 4

Detailed Description:

The study is a two-group parallel design randomised controlled non-inferiority trial and has been registered (ISRCTN23577151). Consented patients with major depressive disorder (DSM-IV) will be randomly allocated to a course of bitemporal (BT) ECT (1.5 x ST) or high-dose right unilateral (RUL) ECT (6.0 x ST). To facilitate generalizability of results, the trial takes place under "real world" conditions and so both groups continue usual care and medications during the treatment phase and thereafter. Patients are followed-up for 12 months after completing their allocated course of ECT. Completion of the primary outcome depression-rating measure (i.e. HDRS) and the secondary outcome of most interest (autobiographical memory, using the AMI-SF) will be prioritised in the data collection.

Patients, their treating clinicians and raters are blind to treatment; clinicians administering ECT are not involved in post randomisation assessments or formal data analysis. Success of blinding for patients and raters will be assessed after the second and final treatments. The trial statistician is also blinded to allocation status.

Sample size: In a large series (n = 253) of depressed patients, Petrides et al. (2001) found a mean (SD) reduction in 24-item HDRS of 25.6 (9.4) after treatment with bitemporalT ECT (1.5 x ST). We therefore estimate that 69 patients will be required per treatment group to have 80% power to demonstrate, using a one-sided equivalence t-test at 5% level, that mean reduction in 24-item HDRS achieved using high-dose RUL ECT is no more than 4 points (i.e. equivalent to 3 points on 17-item HDRS) less than that achieved using standard BT ECT, assuming a common within-group SD of change scores of 9.4 and equal expected group mean change scores.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Controlled Trial of Standard Bilateral Electroconvulsive Therapy Versus High-dose Unilateral Electroconvulsive Therapy for Severe Depression
Study Start Date : May 2008
Actual Primary Completion Date : November 2013
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Bilateral ECT Mecta 5000M
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
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.
Other Name: electroconvulsive therapy Mecta 500M device

Drug: Methohexitone
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.
Other Names:
  • methohexital
  • Brevimytal (Hikma, Germany)

Drug: Suxamethonium
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.
Other Names:
  • Succinylcholine
  • Anectine (GlaxoSmithKline, UK)

Experimental: High-dose unilateral ECT Mecta 5000M
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
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.
Other Name: electroconvulsive therapy Mecta 500M device

Drug: Methohexitone
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.
Other Names:
  • methohexital
  • Brevimytal (Hikma, Germany)

Drug: Suxamethonium
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.
Other Names:
  • Succinylcholine
  • Anectine (GlaxoSmithKline, UK)




Primary Outcome Measures :
  1. Hamilton Depression Rating Scale (HDRS) [ Time Frame: HDRS scores were obtained at baseline, end of allocated ECT treatment, and at 3 and 6 month follow-up timepoints. ]
    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.


Secondary Outcome Measures :
  1. Columbia Autobiographical Memory Interview-Short Form (AMI-SF) [ Time Frame: end of allocated ECT course ]
    The AMI-SF is used to assess retrospective autobiographical memory function. It has six categories, which involve five questions each, about a family member, most recent travel, last New Year's Eve, last birthday, most recent employment and last visit to a doctor for a physical complaint. At baseline interviewers encourage the participant to recall as much information as they can. Responses at baseline can be scored either two points, for a recognisable real memory, or zero for no memory or too little information to constitute a proper memory. Only those questions for which a memory had been retrieved at baseline are examined at follow-up. Follow-up assessments are scored as percentage recall of baseline score, which is scored as 100% irrespective of actual performance..

  2. Columbia Autobiographical Memory Interview-Short Form (AMI-SF) [ Time Frame: 3 months follow-up ]
    The AMI-SF is used to assess retrospective autobiographical memory function. It has six categories, which involve five questions each, about a family member, most recent travel, last New Year's Eve, last birthday, most recent employment and last visit to a doctor for a physical complaint. At baseline interviewers encourage the participant to recall as much information as they can. Responses at baseline can be scored either two points, for a recognisable real memory, or zero for no memory or too little information to constitute a proper memory. Only those questions for which a memory had been retrieved at baseline are examined at follow-up. Follow-up assessments are scored as percentage recall of baseline score, which is scored as 100% irrespective of actual performance..

  3. Columbia Autobiographical Memory Interview-Short Form (AMI-SF) [ Time Frame: 6 months follow-up ]
    The AMI-SF is used to assess retrospective autobiographical memory function. It has six categories, which involve five questions each, about a family member, most recent travel, last New Year's Eve, last birthday, most recent employment and last visit to a doctor for a physical complaint. At baseline interviewers encourage the participant to recall as much information as they can. Responses at baseline can be scored either two points, for a recognisable real memory, or zero for no memory or too little information to constitute a proper memory. Only those questions for which a memory had been retrieved at baseline are examined at follow-up. Follow-up assessments are scored as percentage recall of baseline score, which is scored as 100% irrespective of actual performance..



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients ≥18 years diagnosed with major depressive episode (DSM-IV) and referred for ECT

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01907217


Locations
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Ireland
St Patrick's University Hospital
Dublin, Ireland, 8
Sponsors and Collaborators
St Patrick's Hospital, Ireland
Health Research Board, Ireland
Investigators
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Principal Investigator: Declan M McLoughlin, PhD St Patrick's University Hospital

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Responsible Party: Prof Declan McLoughlin, Professor, St Patrick's Hospital, Ireland
ClinicalTrials.gov Identifier: NCT01907217     History of Changes
Other Study ID Numbers: TRA/2007/5
ISRCTN23577151 ( Registry Identifier: Current Controlled Trials )
First Posted: July 24, 2013    Key Record Dates
Results First Posted: November 14, 2018
Last Update Posted: November 14, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: We are continuing to analyze trial data for secondary analyses. Requests for IPD will be considered where appropriate.

Keywords provided by Prof Declan McLoughlin, St Patrick's Hospital, Ireland:
Electroconvulsive therapy
ECT
electrode placement
effectiveness
cognition
autobiographical memory

Additional relevant MeSH terms:
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Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Anesthetics
Methohexital
Succinylcholine
Central Nervous System Depressants
Physiological Effects of Drugs
Neuromuscular Depolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Anesthetics, Intravenous
Anesthetics, General