Depression, Treatment Resistant Depression, Unipolar Depression
Conditions
Keywords
Depression, Unipolar Depression, Treatment Resistant Depression, Magnetic Seizure Therapy, Suicidal Ideation, Electroconvulsive Therapy
Brief summary
This trial aims to assess the efficacy and tolerability of Magnetic Seizure Therapy (MST) as an alternative to electroconvulsive therapy (ECT) for depression. Even with multiple medication trials, 30 - 40% of patients will experience a pharmacologically resistant form of illness. The ineffectiveness of current treatments for major depressive disorder (MDD) coupled with the 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 two international academic medical centers (the Centre for Addiction and Mental Health in Toronto, Canada and UT Southwestern in Dallas, Texas). The investigators are pursuing a non-inferiority clinical trial in an effort to compare MST - a new treatment for TRD - to 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.
Interventions
DEVICEMagnetic Seizure Therapy
MST treatment will be administered using the MagPro MST with a Cool TwinCoil over the frontal cortex in the midline position using 100 Hz stimulation. The MST determination of seizure threshold will be done using 100% machine output applied at 100 Hz at progressively escalating train durations, commencing at 2 seconds and increasing by 2 seconds with each subsequent stimulation until an adequate seizure is produced. During subsequent sessions, one stimulation will be delivered using a train duration that is 4 seconds longer than the train duration at threshold (with a maximum train duration of 10 seconds). This will be performed under the effect of anesthesia. The treatment procedure is approximately 10 minutes, followed by a recovery period of approximately 30 minutes.
DEVICEElectroconvulsive Therapy
In the ECT arm treatment, the MECTA spectrum 5000Q or the Sigmastim devices will be used, which are FDA approved devices used for providing standard-of-care clinical ECT treatments. The ECT determination of seizure threshold and the adjustment of energy at subsequent sessions will be based on a standard published protocol. All participants will receive RUL-UB ECT at six times the seizure threshold under the effect of anesthesia. The treatment procedure is approximately 10 minutes, followed by a recovery period of approximately 30 minutes
Sponsors
University of Texas Southwestern Medical Center
National Institute of Mental Health (NIMH)
Centre for Addiction and Mental Health
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Participants will be randomized into the study using a permuted block method with a random number generator. The study statistician will prepare the randomization scheme. The block size will be varying and study personnel will be blinded to the randomization block size.
Intervention model description
The study is a randomized, double blind, parallel--group clinical trial with two treatment arms conducted both at the University of Texas Southwestern in Dallas, Texas and at the Temerty Centre for Therapeutic Brain Intervention based at CAMH in Toronto, Canada. Both sites aim to recruit 130 participants each.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 MDD 4. are 18 years of age or older 5. have a baseline HRSD-24 score \> or = 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 \[75\]; 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 \> lorazepam 2 mg/day or equivalent 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission of Depression on the Hamilton Rating Scale for Depression-24 Item (HRSD-24) | Approximately 7 weeks | 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) Remission defined as a HRSD-24 total score of ≤10 and 60% reduction from baseline on two consecutive assessments. The outcome is reported as number of participants meeting remission criteria in each treatment group. |
| Worsening of Autobiographical Memory on the Autobiographical Memory Test (AMT) | Approximately 7 weeks | In the Autobiographical Memory Test (AMT), participants are presented with emotional cue words and asked to retrieve a personal memory within a brief response window; interview formats have been shown to produce fewer specific and more overgeneral memories. The outcome is reported as the number of participants who meet the predefined worsening criterion at follow-up. The binary outcome was defined as a worsening from baseline of \>25% on the AMT total score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission on the Scale for Suicidal Ideation (SSI) | Approximately 7 weeks | Remission of suicidal ideation will be assessed using the Scale for Suicidal Ideation (SSI), a clinician-administered tool with 19 scored items rated 0-2, total score range 0-38. Higher scores indicate greater suicidal ideation severity. Remission is defined as an SSI total score of 0 at follow-up. The outcome is the number of participants who meet remission criteria compared with baseline. |
| Response on the Hamilton Rating Scale for Depression-24 Item (HRSD-24) | Approximately 7 weeks | 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) Response is defined as a HRSD-24 reduction of 50% or greater from baseline The outcome is reported as number of participants meeting response criteria in each treatment group. |
| Score on the Brief Symptom Inventory Anxiety Section (BSI-A) | Approximately 7 weeks | The Brief Symptom Inventory (BSI) anxiety section (ANX) is a subscale comprised of 6 items designed to measure subjective experiences of tension, panic, and restlessness over the past week. It uses a 5-point Likert scale (0=not at all to 4=extremely) to identify symptoms like "nervousness," "feeling tense," or "spells of terror". Higher = worse; lower = better. The total score ranges from 0 to 24. |
| Response on the Clinical Global Impression - Improvement Scale (CGI-I) | Approximately 7 weeks | The Clinical Global Impression-Improvement (CGI-I) scale is a 7-point, observer-rated tool used to measure how much a patient's illness has improved or worsened relative to their baseline. It is rated from 1 (very much improved) to 7 (very much worse). Response is defined as a CGI-I score of 1 or 2. |
| Score on the Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Approximately 7 weeks | The Q-LES-Q-SF (Short Form) measures quality of life through 14 items, each rated on a 1-5 scale (1=Very Poor, 5=Very Good). Total raw scores range from 14 to 70, with higher scores indicating greater satisfaction. |
| Score on the Columbia ECT Subjective Side Effects Schedule (CSSES) | Approximately 7 weeks | The Columbia ECT Subjective Side Effects Schedule is a tool used to monitor adverse effects after each ECT session and at baseline. It tracks physical, cognitive, and mood side effects. For the physical scale (range 0-15) and cognitive scale (range 0-6) it uses a 4-point Likert-type scale where 0 = none; 1 = yes, mild; 2 = yes, moderate; and 3 = yes, severe. For the mood scale (range 0-3) it uses a 2-point Likert-type scale where 0 = no; 1 = yes. For the physical and cognitive scales, higher values indicate a worse outcome. For the mood scale, higher values indicate a better outcome. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORDaniel Blumberger, MD
Centre for Addiction and Mental Health
Participant flow
Pre-assignment details
Out of 119 allocated to MST arm, 2 Did not receive allocated intervention. Out of 120 allocated to ECT arm, 1 Did not receive allocated intervention.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 45 Years STANDARD_DEVIATION 14.3 |
| Race/Ethnicity, Customized Race American Indian/Alaska native | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 7 Participants |
| Race/Ethnicity, Customized Race Black or African American | 6 Participants |
| Race/Ethnicity, Customized Race More than one race | 1 Participants |
| Race/Ethnicity, Customized Race Other | 7 Participants |
| Race/Ethnicity, Customized Race Unknown or not reported | 2 Participants |
| Race/Ethnicity, Customized Race White | 100 Participants |
| Sex: Female, Male Female | 135 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 117 | 0 / 119 |
| other Total, other adverse events | 114 / 117 | 119 / 119 |
| serious Total, serious adverse events | 8 / 117 | 2 / 119 |
Outcome results
None listed