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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Outcomes Assessor);   Primary Purpose: Treatment
Condition Depression
Interventions Device: ECT Mecta 5000M
Drug: Methohexitone
Drug: Suxamethonium
Enrollment 138
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Hide Arm/Group Description

Twice-weekly 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.

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.

Twice-weekly 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.

Seizure threshold (ST) is established by a method of limits at the first session and subsequent treatments will be given at 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.

Period Title: Overall Study
Started 69 69
Completed 69 67
Not Completed 0 2
Reason Not Completed
Withdrawal by Subject             0             2
Arm/Group Title Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M Total
Hide Arm/Group Description

Twice-weekly 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.

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.

Twice-weekly 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.

Seizure threshold (ST) is established by a method of limits at the first session and subsequent treatments will be given at 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.

Total of all reporting groups
Overall Number of Baseline Participants 69 69 138
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 69 participants 69 participants 138 participants
56.8  (14.4) 56.6  (15.3) 56.7  (14.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 69 participants 138 participants
Female
47
  68.1%
40
  58.0%
87
  63.0%
Male
22
  31.9%
29
  42.0%
51
  37.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 69 participants 138 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
69
 100.0%
69
 100.0%
138
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Ireland Number Analyzed 69 participants 69 participants 138 participants
69 69 138
1.Primary Outcome
Title Hamilton Depression Rating Scale (HDRS)
Hide Description 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.
Time Frame HDRS scores were obtained at baseline, end of allocated ECT treatment, and at 3 and 6 month follow-up timepoints.
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat analysis.
Arm/Group Title Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Hide Arm/Group Description:

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.

Seizure duration is measured by EEG monitoring. 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.

Modified 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.

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.

Overall Number of Participants Analyzed 69 69
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 69 participants 69 participants
29.5  (6.3) 30.4  (6.1)
End-of-treatment Number Analyzed 69 participants 67 participants
12.5  (9.2) 11.1  (7.5)
3 months follow-up Number Analyzed 53 participants 60 participants
15.0  (10.2) 11.5  (9.1)
6 months follow-up Number Analyzed 50 participants 55 participants
13.0  (8.6) 12.6  (10.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bilateral ECT Mecta 5000M, High-dose Unilateral ECT Mecta 5000M
Comments Based on a large bitemporal ECT series, we estimated that 69 patients were required per group to have 80% power to demonstrate, using a one-sided equivalence t test at 5% level, that the mean reduction in the 24-item HAM-D score following high-dose unilateral ECT was no more than 4 points (i.e., equivalent to 3 points on the 17-item HAM-D, deemed to be clinically relevant [30]) less than that achieved using bitemporal ECT.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

The prespecified noninferiority margin was no more than a –4 point difference at the end of treatment between the bilateral and unilateral groups.

The predicted difference at the end of treatment was 1.08 (95% confidence interval [CI] = –1.67 to 3.84.

Statistical Test of Hypothesis P-Value <0.05
Comments Primary statistical analysis was assessment of difference in HAM-D scores between arms at end-of-treatment, supplemented by 95% CIs and this interval compared with the pre-specified noninferiority threshold (-4 points). The p-value was calculated.
Method Regression, Linear
Comments A regression model was fitted to end-of-treatment HAM-D measures, with baseline HAM-D scores, trial arm, randomization stratifiers as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
-1.67 to 3.84
Estimation Comments The prespecified noninferiority margin was no more than a –4-point difference at the end of treatment between bitemporal and unilateral groups. The predicted difference at the end of treatment was 1.08 (95% confidence interval [CI]=–1.67 to 3.84).
2.Secondary Outcome
Title Columbia Autobiographical Memory Interview-Short Form (AMI-SF)
Hide Description 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..
Time Frame end of allocated ECT course
Hide Outcome Measure Data
Hide Analysis Population Description
Not all patients completed this cognitive task.
Arm/Group Title Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Hide Arm/Group Description:

Twice-weekly 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.

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.

Twice-weekly 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.

Seizure threshold (ST) is established by a method of limits at the first session and subsequent treatments will be given at 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.

Overall Number of Participants Analyzed 64 64
Mean (Standard Deviation)
Unit of Measure: % of baseline performance
56.8  (17.3) 67.1  (16.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bilateral ECT Mecta 5000M, High-dose Unilateral ECT Mecta 5000M
Comments The AMI-SF at end of treatment was analyzed using generalized linear models with a binomial distribution and logit-link. Post treatment AMI-SF measures provide the number of baseline items recalled after ECT; such “number of items recalled” variables were therefore modeled as arising from binomial distributions, with maximum number of possible recalls set to the number of items obtained at baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments As above
Method generalized linear models with a binomia
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.51 to 0.85
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Columbia Autobiographical Memory Interview-Short Form (AMI-SF)
Hide Description 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..
Time Frame 3 months follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Not all patients completed this cognitive task.
Arm/Group Title Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Hide Arm/Group Description:

Twice-weekly 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.

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.

Twice-weekly 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.

Seizure threshold (ST) is established by a method of limits at the first session and subsequent treatments will be given at 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.

Overall Number of Participants Analyzed 48 56
Mean (Standard Deviation)
Unit of Measure: % of baseline performance
56.2  (18.1) 67.3  (14.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bilateral ECT Mecta 5000M, High-dose Unilateral ECT Mecta 5000M
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Regression, Linear
Comments Analyzed using a generalized linear models with a binomial distribution and logit-link.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.45 to 0.78
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Columbia Autobiographical Memory Interview-Short Form (AMI-SF)
Hide Description 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..
Time Frame 6 months follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Not all patients completed this cognitive task.
Arm/Group Title Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Hide Arm/Group Description:

Twice-weekly 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.

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.

Twice-weekly 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.

Seizure threshold (ST) is established by a method of limits at the first session and subsequent treatments will be given at 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.

Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: % of baseline performance
52.9  (16.4) 63.4  (17.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bilateral ECT Mecta 5000M, High-dose Unilateral ECT Mecta 5000M
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Regression, Linear
Comments generalized linear models with a binomial distribution and logit-link
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.45 to 0.79
Estimation Comments [Not Specified]
Time Frame Participants were monitored for ECT-related adverse events during individual ECT sessions and throughout the ECT treatment course, an average of four weeks per participant. They were also monitored for any other adverse events (not directly related to treatment with ECT) throughout the six month follow-up.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Hide Arm/Group Description

Twice-weekly 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.

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.

Twice-weekly 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.

Seizure threshold (ST) is established by a method of limits at the first session and subsequent treatments will be given at 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.

All-Cause Mortality
Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/69 (13.04%)      7/69 (10.14%)    
Cardiac disorders     
ECT-related hypertension  [1]  2/69 (2.90%)  2 4/69 (5.80%)  4
tachyarrhythmia  [2]  1/69 (1.45%)  1 1/69 (1.45%)  1
bradyarrhythmia   1/69 (1.45%)  1 0/69 (0.00%)  0
Nervous system disorders     
interictal confusion  [3]  3/69 (4.35%)  3 0/69 (0.00%)  0
Psychiatric disorders     
attempted suicide  [4]  0/69 (0.00%)  0 1/69 (1.45%)  1
Respiratory, thoracic and mediastinal disorders     
laryngospasm  [5]  0/69 (0.00%)  0 1/69 (1.45%)  1
Bronchospasm   1/69 (1.45%)  1 0/69 (0.00%)  0
pulmonary embolus * [6]  1/69 (1.45%)  1 0/69 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
required beta-blockers for ECT-related hypertension
[2]
one patient developed tachyarrhythmia necessitating ECT termination
[3]
three patients developed interictal confusion resulting in postponement/termination of ECT
[4]
one patient attempted suicide during the course of ECT
[5]
one patient developed laryngospasm with temporary drop in oxygen saturation
[6]
one patient developed a pulmonary embolus after the fifth treatment.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bilateral ECT Mecta 5000M High-dose Unilateral ECT Mecta 5000M
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   33/69 (47.83%)      37/69 (53.62%)    
Gastrointestinal disorders     
nausea  [1]  8/69 (11.59%)  8 11/69 (15.94%)  11
Musculoskeletal and connective tissue disorders     
muscle pain  [2]  6/69 (8.70%)  6 8/69 (11.59%)  8
Nervous system disorders     
Headache  [3]  19/69 (27.54%)  19 18/69 (26.09%)  18
Indicates events were collected by systematic assessment
[1]
post ECT nausea, requiring anti emetic
[2]
post ECT muscle pain, mild and transient
[3]
Post ECT headache, mild and transient
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.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof Declan McLoughlin
Organization: St Patrick's University Hospital
Phone: +353 1 2493343
EMail: d.mcloughlin@tcd.ie
Layout table for additonal information
Responsible Party: Prof Declan McLoughlin, 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 Submitted: June 16, 2013
First Posted: July 24, 2013
Results First Submitted: December 21, 2016
Results First Posted: November 14, 2018
Last Update Posted: November 14, 2018