Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST)

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST - MST)

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.

Study Overview

• Status: Completed
• Conditions: Depression; Treatment Resistant Depression; Unipolar Depression
• Intervention / Treatment: Device: Magnetic Seizure Therapy; Device: Electroconvulsive Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6J 1H4
      • Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health
• United States
  • California
    • San Diego, California, United States, 92127
      • University of California San Diego
  • Texas
    • Dallas, Texas, United States, 75390-9127
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnetic Seizure Therapy (MST); MST treatments will be administered using the MagPro MST with Cool TwinCoil.	Device: Magnetic 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.; Other Names: MST
Active Comparator: Electroconvulsive Therapy (ECT); ECT treatments will be administered using the MECTA spECTrum 5000Q or the Sigmastim devices.	Device: Electroconvulsive 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; Other Names: ECT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission of Depression on the Hamilton Rating Scale for Depression-24 Item (HRSD-24)	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.	Approximately 7 weeks
Worsening of Autobiographical Memory on the Autobiographical Memory Test (AMT)	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.	Approximately 7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission on the Scale for Suicidal Ideation (SSI)	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.	Approximately 7 weeks
Response on the Hamilton Rating Scale for Depression-24 Item (HRSD-24)	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.	Approximately 7 weeks
Score on the Brief Symptom Inventory Anxiety Section (BSI-A)	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.	Approximately 7 weeks
Response on the Clinical Global Impression - Improvement Scale (CGI-I)	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.	Approximately 7 weeks
Score on the Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)	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.	Approximately 7 weeks
Score on the Columbia ECT Subjective Side Effects Schedule (CSSES)	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.	Approximately 7 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute of Mental Health (NIMH); University of California, San Diego; Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Daniel Blumberger, MD, Centre for Addiction and Mental Health

Publications and helpful links

General Publications

• Daskalakis ZJ, McClintock SM, Hadas I, Kallioniemi E, Zomorrodi R, Throop A, Palmer L, Farzan F, Thorpe KE, Tamminga C, Blumberger DM. Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): protocol for identification of novel biomarkers via neurophysiology. Trials. 2021 Dec 11;22(1):906. doi: 10.1186/s13063-021-05873-7.
• Daskalakis ZJ, Tamminga C, Throop A, Palmer L, Dimitrova J, Farzan F, Thorpe KE, McClintock SM, Blumberger DM. Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): study protocol for a randomized non-inferiority trial of magnetic seizure therapy versus electroconvulsive therapy. Trials. 2021 Nov 8;22(1):786. doi: 10.1186/s13063-021-05730-7.
• Regenold WT, Deng ZD, Lisanby SH. Noninvasive neuromodulation of the prefrontal cortex in mental health disorders. Neuropsychopharmacology. 2022 Jan;47(1):361-372. doi: 10.1038/s41386-021-01094-3. Epub 2021 Jul 16.
• Jiang J, Zhang C, Li C, Chen Z, Cao X, Wang H, Li W, Wang J. Magnetic seizure therapy for treatment-resistant depression. Cochrane Database Syst Rev. 2021 Jun 16;6(6):CD013528. doi: 10.1002/14651858.CD013528.pub2.
• Blumberger DM, McClintock SM, Thorpe KE, Tamminga CA, Foley K, Husain MM, Kaster TS, Knyahnytska Y, Voineskos D, Bailey KJ, Hubregsen JJ, Weissman CR, Daskalakis ZJ. Confirmatory efficacy and safety trial of magnetic seizure therapy versus right unilateral ultra-brief electroconvulsive therapy in depression (CREST-MST): a randomised, double-blind, non-inferiority trial in Canada and the USA. Lancet Psychiatry. 2026 May;13(5):376-386. doi: 10.1016/S2215-0366(26)00060-X.

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2018
• Primary Completion (Actual): November 22, 2024
• Study Completion (Actual): November 22, 2024

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (Actual): June 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Electroconvulsive Therapy; Treatment Resistant Depression; Suicidal Ideation; Unipolar Depression; Magnetic Seizure Therapy
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Self-Injurious Behavior; Mood Disorders; Suicide; Behavior; Suicidal Ideation; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: STU 032017-022; 1R01MH112815-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No