Efficacy of Convulsive Therapies for Bipolar Depression

Not Applicable

Completed

• Conditions: Bipolar Depression; Bipolar I Disorder; Bipolar II Disorder; Bipolar Disorder
• Interventions: Device: Magnetic Seizure Therapy (MST); Device: Electroconvulsive Therapy (ECT)

• Registration Number: NCT03641300
• Lead Sponsor: Centre for Addiction and Mental Health

Brief Summary

This trial aims to assess the efficacy and tolerability of Magnetic Seizure Therapy (MST) as an alternative to electroconvulsive therapy (ECT) for Bipolar Disorder (BD). Research indicates that the prevalence of treatment resistance in bipolar depression is twice that of unipolar depression. The limited effectiveness of current treatments for bipolar depression coupled with the medical and economic burden associated with the disorder engenders a need for novel therapeutic interventions that can provide greater response and remission rates.

Detailed Description

The study will involve a randomized, double blind, non-inferiority clinical trial with two treatment arms conducted in three academic institutions (the Centre for Addiction and Mental Health (CAMH) in Toronto, Ontario; the Ontario Shores Centre for Mental Health Sciences in Whitby, Ontario; and University of British Columbia (UBC) Hospital in Vancouver, British Columbia). The investigators are pursuing a non-inferiority clinical trial in an effort to compare MST to right unilateral ultrabrief pulse ECT (RUL-UB-ECT). Treatment will be administered two to three days per week. Depression symptoms will be assessed with the 24-item Hamilton Depression Rating Scale (HRSD-24) and suicidality will be assessed with the Scale for Suicidal Ideation (SSI). Remission will be defined as HRSD-24 \< or = 10 and a \> 60% decrease in scores from baseline on two consecutive ratings. Once a participant reaches remission, a second rating to confirm remission will be conducted immediately before their next scheduled treatment. If remission is confirmed, they will then be considered a completer of the acute treatment course. Remission of suicidal ideation is defined as a score of 0 on the SSI. Therefore, there will be no specific minimum number of treatments that patients must receive to be classified as remitters. However, patients who do not meet remission criteria after 21 treatment sessions will be considered non-remitters and will cease treatment sessions. This maximum treatment number was chosen allowing for the possibility that MST may require more treatment sessions to achieve remission, similar to RUL-UB ECT. The blind will not be broken to participants until the completion of the entire study.

Study Timeline

• Study First Submitted: 2018-08-17
• Study First Submitted QC: 2018-08-17
• Study First Posted: 2018-08-22
• Study Start: 2018-09-21
• Primary Completion: 2024-03-04
• Study Completion: 2024-08-09
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-01
• Last Update Posted: 2024-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

Patients will be included if they:

1. are inpatients or outpatients;
2. are voluntary and competent to consent to treatment and research procedures according to ECT/MST attending psychiatrist;
3. have a MINI International Neuropsychiatric Interview diagnosis, Version 6 (MINI-6.0) diagnosis of non-psychotic Bipolar Disorder (Type I or II)
4. are 18 years of age or older
5. have a baseline HRSD-24 score > 21;
6. are considered to be appropriate to receive convulsive therapy as assessed by an ECT attending psychiatrist and a consultant anaesthesiologist
7. are agreeable to keeping their current antidepressant treatment constant during the intervention;
8. are likely able to adhere to the intervention schedule;
9. meet the MST safety criteria;
10. If a woman of child-bearing potential: is willing to provide a negative pregnancy test and agrees not to become pregnant during trial participation.

Exclusion Criteria

Patients will be excluded if they:

1. have a history of MINI diagnosis of substance dependence or abuse within the past three months;

2. have a concomitant major unstable medical illness;

3. are pregnant or intend to get pregnant during the study;

4. have a MINI diagnosis of any primary psychotic disorder

5. have a MINI diagnosis of obsessive compulsive disorder, or post-traumatic stress disorder deemed to be primary and causing more functional impairment than the depressive disorder

6. have probable dementia based on study investigator assessment;

7. have any significant neurological disorder or condition likely to be associated with increased intracranial pressure or a space occupying brain lesion, e.g., cerebral aneurysm;

8. present with a medical condition, a medication, or a laboratory abnormality that could cause a major depressive episode or significant cognitive impairment in the opinion of the investigator (e.g., hypothyroidism with low TSH, rheumatoid arthritis requiring high dose prednisone, or Cushing's disease);

9. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;

10. require a benzodiazepine with a dose greater than lorazepam 2 mg/day (or equivalent benzodiazepine) or any anticonvulsant due to the potential of these medications to limit the efficacy of both MST and ECT;

11. are unable to communicate in English fluently enough to complete the neuropsychological tests;

12. have a non-correctable clinically significant sensory impairment (i.e., cannot hear or see well enough to complete the neuropsychological tests).

    These eligibility criteria are congruent with the criteria that have been used in the major ECT trials conducted during the past decade;

13. elevated mood, defined as a score of 20 or higher on the Young Mania Rating Scale (YMRS).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Magnetic Seizure Therapy (MST)	Magnetic Seizure Therapy (MST)	MST treatments will be administered using the MagPro MST with Cool TwinCoil.
Electroconvulsive Therapy (ECT)	Electroconvulsive Therapy (ECT)	ECT treatments will be administered using the MECTA spECTrum 5000Q or MECTA Sigma

Primary Outcome Measures

Name	Time	Method
Cognitive adverse effects as indexed by the Autobiographical Memory Test (AMT)	Greater than 8 treatments (2.5 weeks)	Autobiographical Memory Test: - Interviewer-rated measure with 10 items that indexes autobiographical memory recall and specificity.
Remission (score </= 10) on the Hamilton Rating Scale for Depression - 24 (HRSD-24)	Greater than 8 treatments (2.5 weeks)	Hamilton Rating Scale for Depression (24-item version): * This scale is used to quantify the severity of symptoms of depression; * Scale range: 0-76 (total score); * Lower scores indicate lower severity of depressive symptoms (i.e., better outcome); * Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome)

Secondary Outcome Measures

Name	Time	Method
Improvement in symptom severity of Suicidal Ideation as measured by the Scale for Suicidal Ideation (SSI)	7 weeks	Scale for Suicidal Ideation: * This scale is used to assess the presence or absence of suicidal ideation and the degree of severity of suicidal ideas; * Scale range: 0 - 38 (total score); * Lower scores indicate lower severity of suicidal ideation (i.e., better outcome); * Higher scores indicate higher severity of suicidal ideation (i.e., worse outcome)
Number of self-reported and clinical-reported adverse events	Up to 7 weeks	Number of adverse events in both treatment arms

Trial Locations

Locations (3)

Ontario Shores Centre for Mental Health Sciences; 🇨🇦 Whitby, Ontario, Canada

UBC Hospital, University of British Columbia (UBC); 🇨🇦 Vancouver, British Columbia, Canada

Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health; 🇨🇦 Toronto, Ontario, Canada