Enhancing the Effectiveness of Electroconvulsive Therapy in Severe Depression

Depression Clinical Trial

— EFFECT-Dep  

Official title:

A Randomised Controlled Trial of Standard Bilateral Electroconvulsive Therapy Versus High-dose Unilateral Electroconvulsive Therapy for Severe Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01907217
• Other study ID #: TRA/2007/5
• Secondary ID: ISRCTN23577151
• Status: Completed
• Phase: Phase 4
• Start date: May 2008
• Est. completion date: April 2015

Study information

• Verified date: April 2018
• Source: St Patrick's Hospital, Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: April 2015
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

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.

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.
• 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.

Locations

Country	Name	City	State
Ireland	St Patrick's University Hospital	Dublin

Sponsors (2)

Lead Sponsor	Collaborator
St Patrick's Hospital, Ireland	Health Research Board, Ireland

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Columbia Autobiographical Memory Interview-Short Form (AMI-SF)	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..	end of allocated ECT course
Secondary	Columbia Autobiographical Memory Interview-Short Form (AMI-SF)	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 months follow-up
Secondary	Columbia Autobiographical Memory Interview-Short Form (AMI-SF)	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..	6 months follow-up